bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Tyrosine Kinase Inhibitors Block the Stimulatory Actions of Phosphotyrosine Phosphatase Inhibitors to Increase Cell Proliferation, Alkaline Phosphatase Activity, and Collagen Synthesis in Normal HumanBone Cells
Authors: Yoon Hyun Koo , Baylink David J. , Lau K.-H. William
Published: April 2003

The present study sought to test whether inhibition of phosphotyrosine phosphatases (PTPs) would stimulate proliferation and differentiation of normal bone cells, and whether the PTP inhibitor-mediated effects would be blocked by protein tyrosine kinase (PTK) inhibitors. Three inhibitors [phenylarsine oxide (PAO), orthovanadate (VO4), and molybdate (MoO4)] and two normal human bone cells with different basal differentiation status (i.e., mandible- and vertebra-derived bone cells) were used. Cell proliferation was determined with [3H]thymidine incorporation, and confirmed by cell counting. Bone cell differentiation was assessed by increases in alkaline phosphatase (ALP) specific activity and collagen synthesis. The three test PTP inhibitors each stimulated [3H]thymidine incorporation in both human bone cell types in a biphasic, dose-dependent manner with optimal doses of 20 nM PAO, 1 μM VO4 and 2 μM MoO4, respectively. These PTP inhibitors at mitogenic doses each significantly and reproducibly increased ALP specific activity and collagen synthesis. To determine whether the stimulatory effects of PTP inhibitors could be blocked by PTK inhibitors, the effects of tyrphostin A51 and erbstatin, two potent PTK inhibitors, on the actions of PTK inhibitors on [3H]thymidine incorporation and ALP specific activity were evaluated. Both tyrphostin A51 and erbstatin, which by themselves alone significantly inhibited human bone cell proliferation and increased ALP specific activity, completely abolished the stimulatory effects of each of the three test PTP inhibitors on bone cell proliferation and ALP specific activity. In conclusion, these findings confirm the premise that inhibition of PTP activities in normal human bone cells could lead to increases in cell proliferation and differentiation, effects that are independent of basal differentiation status of the cells. More importantly, this study demonstrates for the first time that the stimulatory actions of the PTP inhibitor on bone cell proliferation and ALP could be blocked by a PTK inhibitor, suggesting that the osteogenic effects of PTP inhibitors may depend on PTK activities, presumably to increase basal tyrosyl phosphorylation level. Accordingly, one should interpret results of studies using PTK inhibitors with caution in that an inhibition by a PTK inhibitor does not necessarily indicate the requirement of PTK activities, as it could also suggest involvement of an inhibition of PTPs.
The Urinary Podocyte as a Marker for the Differential Diagnosis of Idiopathic Focal Glomerulosclerosis and Minimal-Change Nephrotic Syndrome
Authors: Nakamura Tsukasa , Ushiyama Chifuyu , Suzuki Shingo , Hara Masanori , Shimada Noriaki , Ebihara Isao , Koide Hikaru
Published: April 2003

Background/Aims: Detection of podocytes in the urine sediment of children indicates that severe podocyte injury occurred in the glomerulus. Focal glomerulosclerosis (FGS) and minimal-change nephrotic syndrome (MCNS) are kidney diseases characterized by massive proteinuria. The aim of the present study was to determine whether urinary podocytes can be detected in patients with idiopathic FGS or MCNS and whether immunosuppression therapy alters these cells. Methods: Twenty patients with MCNS (nephrotic stage, n = 12; remission stage, n = 8), 15 patients with FGS and 20 healthy controls were included in the present study. Urinary podocytes were stained by immunofluorescence. All patients with MCNS at the nephrotic stage received prednisolone for 6 months, and all patients with FGS received some form of immunosuppression therapy including prednisolone, cyclophosphamide or mizoribine for 12 months. Results: The 12 nephrotic-stage MCNS patients achieved remission after treatment. Seven of the 15 FGS patients also achieved remission, but the other 8 remained in the nephrotic stage. Urinary podocytes were not detected in any patient with MCNS nor were they detected in healthy controls. Urinary podocytes were detected in all FGS patients (mean, 4.2 cells/ml) before treatment and the number of cells decreased in the 7 patients who achieved remission. The number of podocytes was unchanged in the other 8 patients even after treatment. Conclusion: Urinary podocytes may be a useful diagnostic indicator for differentiation between FGS and MCNS. These cells may also mark disease progression in cases of FGS.
Insulin-Like Growth Factor I Correlates with Protein Intake Estimated from the Normalized Protein Catabolic Rate in Hemodialysis Patients
Authors: Lindgren Björn F. , Friis Karin , Ericsson Folke
Published: April 2003

Background/Aim: Malnutrition and catabolism are predominant problems in patients undergoing hemodialysis. The aim of this study was to clarify the relationship between insulin-like growth factor I (IGF-I), the serum levels of which are influenced by nutrition and which by itself promotes amino acid uptake, and insulin-like growth factor binding protein 1 (IGFBP-1), known to regulate serum (s) IGF-I and protein intake, in end-stage renal disease patients. Methods: Thirty hemodialysis patients were studied, and s-IGF-I and s-IGFBP-1 levels were measured by radioimmunoassay. The s-IGF-I method used was validated according to a reference method. The s-IGF-I standard deviation (SD) score was calculated, giving the individual deviation from the mean of a reference population. The protein intake was estimated both directly by 3-day food recall by a dietician and indirectly by normalized protein catabolic rate (PCRn). Results: The mean serum IGF-I level was 166 ± 10 μg/l, corresponding to a normal s-IGF-I SD score (0.5 ± 0.3). S-IGFBP-1 was elevated threefold to 101 ± 11 μg/l as compared with normal subjects. The s-albumin was 39.9 ± 0.5 g/l and the s-bicarbonate 24 ± 0.4 mmol/l. There were significant correlations between s-IGF-I SD score or s-IGF-I (log-transformed) and PCRn (r = 0.37, p < 0.004, and r = 0.41, p < 0.001, respectively). The s-IGF-I/s-IGFBP-1 ratio was also positively correlated with PCRn (rs = 0.36, p < 0.007, by Spearman’s rank correlation). The s-albumin was inversely correlated with log s-IGFBP-1 (r = –0.38, p < 0.01) and positively with the s-IGF-I/s-IGFBP-1 ratio (r = 0.36, p < 0.007) but not with s-IGF-I (p < 0.13). Serum total cholesterol, triglycerides, and total body fat as percentage of body weight correlated with s-IGF-I (r = 0.47, p < 0.004, r = 0.45, p < 0.01, and r = 0.42, p < 0.004, respectively) as well as with the s-IGF-I SD score. No correlations were seen between s-IGF-I and protein or caloric intake by direct estimates from dietary food recalls. Conclusions: The s-IGF-I and the s-IGF-I/s-IGFBP-1 ratio were correlated with estimates of protein intake of the patients calculated from urea kinetics (PCRn) but not with direct estimates by the dietitian. The s-IGF-I SD score and the ratio s-IGF-I/s-IGFBP-1 might be a tool to monitor anabolic status and to select hemodialysis patients for therapeutic intervention with recombinant human IGF-I and/or recombinant human growth hormone to counteract catabolism.
Detection of Cardiac Calcinosis in Hemodialysis Patients by Whole-Body Scintigraphy with 99m-Technetium Methylene Diphosphonate
Authors: Eguchi Mariko , Tsuchihashi Kazufumi , Takizawa Hideki , Nakahara Narifumi , Hagiwara Makoto , Ohnishi Hirofumi , Torii Taka-aki , Hashimoto Akiyoshi , Marusaki Shigeru , Nakata Tomoaki , Ura Nobuyuki , Shimamoto Kazuaki
Published: April 2003

A noninvasive method for the diagnosis of cardiac calcinosis, a life-threatening complication in hemodialysis patients with end-stage renal disease (ESRD), has not, as yet, been firmly established. We tested whether whole body scanning with 99m-technetium methylene diphosphonate (MDP) might visualize cardiac calcinosis. In 19 consecutive chronic hemodialysis ESRD patients (13 males and 6 females, aged 40–81, mean 63 ± 8 years) with cardiovascular disease [mitral annular calcinosis and/or calcified aortic valve (n = 4), hemodialysis cardiomyopathy (n = 1), coronary artery disease (n = 9) and peripheral artery atherosclerotic disease (n = 6)], MDP uptake in the heart was compared to that in 7 non-ESRD controls with hyperparathyroidism due to adenoma. Cardiac and lung field MDP uptake was confirmed in only 3 (16%) and 5 (26%) of the 19 ESRD subjects, respectively, but was absent in controls. Positive cardiac uptake was related to cardiac calcified complications (mobile intracardiac calcinosis, myocardial calcinosis and mitral annular calcification) and the duration of hemodialysis (p = 0.015). While it was statistically insignificant, subjects showing MDP uptake were elder and had higher serum Ca or Ca × P product and lower intact parathyroid hormone levels. These results suggest that cardiac calcinosis in ESRD patients can be detected noninvasively by myocardial scintigraphy with 99m-technetium MDP.
Membranous Glomerulonephritis with Nephrotic Syndrome Associated with Chronic Lymphocytic Leukemia
Authors: Yahata Naoyuki , Kawanishi Yoshikazu , Okabe Seiichi , Kimura Yukihiko , Okada Tomonari , Otani Masako , Shimizu Tohru , Nakao Toshiyuki , Ohyashiki Kazuma
Published: April 2003

A 66-year-old woman was admitted to our hospital for evaluation of edema of the extremities. Laboratory findings suggested that she had nephrotic syndrome and chronic lymphocytic leukemia (CLL). Renal biopsy (with PAM staining) showed a spike formation in the capillary wall. Immunofluorescent staining revealed deposition of immunoglobulin G (IgG) and the third component of complement in the glomerular basement membrane. Electron microscopy showed fibrillary deposits in the subepithelium. These findings indicated membranous glomerulonephritis (MGN). In addition, focal segmental sclerosis and interstitial lymphocytic infiltration were observed in the renal biopsy specimen. In CLL patients nephrotic syndrome occurs rarely. Even if the complication occurs, MGN is not frequent. Both diseases are suspected to occur in association with each other, and immunologic abnormality contributes to their coexistence. Although administration of prednisolone and endoxan improved leukocytosis, proteinuria was not sufficiently improved with combination therapy.
Tod in der Frauenklinik
Authors: Petersen Peter
Published: April 2003

Aufgrund umfangreicher Studien der letzten 70 Jahre in den westlichen Industrieländern und aufgrund eigener psychotherapeutischer Erfahrungen in 36 Jahren lassen sich bei der seelischen Verarbeitung des Schwangerschaftsabbruchs vier Dimensionen des Erlebens unterscheiden. 1. Normalpsychologische Bewältigung (seelische Stabilisierung mit tiefenpsychologisch kennzeichenbaren Abwehrformen); 2.  Durchbruch destruktiver Tiefenerlebnisse (Panik, archaische Ängste); 3. Akzeptieren individueller Verantwortung und existentieller Wirklichkeit, und 4. Zwischenmenschlichkeit in der Beziehung zum toten Kind. Ihre Unterscheidung ist hilfreich zum besseren Verständnis in Therapieprozessen und in der Beratung, abgesehen vom wissenschaftlichen Wert.
Komplextheorie gestern und heute
Authors: Kast Verena
Published: April 2003

Leider besteht für diesen Artikel keine Zusammenfassung. Als Einstieg stellen wir den Textanfang zur Verfügung.Hier an der ETH in Zürich hat C.G. Jung am 5. Mai 1934 seine Antrittsvorlesung zum Thema «Allgemeines zur Komplextheorie» gehalten. Er trug dabei die Quintessenz aus 30 Jahren empirischer Forschung und therapeutischer Erfahrung vor. Seine Antrittsvorlesung an der Universität vom 21. Oktober 1905 hielt er zum Thema «Die psychopathologische Bedeutung des Assoziationsexperimentes». Durch das Assoziationsexperiment hatte Jung die Komplexe entdeckt und diese als Ursache von Neurosen erkannt. In seiner Antrittsvorlesung von 1934 an der ETH stellte er das faszinierende Konzept der Komplexe, das seine Bedeutung auch bis heute nicht verloren hat, in einem Zusammenhang dar, äusserte aber auch, im Zusammenhang mit der Komplextheorie, grundsätzliche Überlegungen zur Forschung im Bereich der Psychotherapie. Dass die Komplextheorie ein zentrales Konzept im Verständnis von Jung war und blieb, ist einem Brief vom 19. Januar 1935 zu entnehmen: Jung soll einen Vortrag vor dem Holländischen Verein für Psychotherapie über «Grundsätzliches zur praktischen Psychotherapie» halten, und er entschliesst sich zu einer allgemeinen Darstellung der Komplextheorie und der praktischen Traumanalyse [Jung, 1935, p. 238]. Das heisst, die Komplextheorie war für ihn ein Herzstück der Psychotherapie.
Forschungskolloquium am C.G.-Jung-Institut Zürich
Authors: Schlegel Mario
Published: April 2003

//8XWährend der beiden Wochen, in denen das C.G.-Jung-Institut Zürich sein 50jähriges Jubiläum feierte, hat es neu in seinem Vorlesungsverzeichnis ein Forschungskolloquium aufgeführt, das zur permanenten öffentlich zugänglichen Einrichtung werden soll. Geleitet wird es von Verena Kast, Guido Mattanza und Mario Schlegel. Dieses zeitliche Zusammentreffen regt zur Reflexion über die Forschung in der Jungschen Psychologie an, denn im Zusammenhang mit neuen Entwicklungen in der Welt der Wissenschaft ergeben sich interessante Perspektiven.
Selbstorganisation – Ordnung aus dem Chaos
Authors: Schröer Sigrid
Published: April 2003

Leider besteht für diesen Artikel keine Zusammenfassung. Als Einstieg stellen wir den Textanfang zur Verfügung.Seit den Entdeckungen von Ilya Prigogine [Prigogine und Stengers, 1981] haben Wissenschaftler aus verschiedensten Forschungsbereichen Systeme entdeckt, die nach einer Phase der Ordnung in eine chaotische oder ungeordnete Phase übergehen, um schliesslich zu einem neuen Stadium einer komplexen Ordnung zu gelangen, einer Ordnung, die der gegenwärtigen Situation besser angepasst ist. Nach Beobachtungen von Prigogine ist das plötzliche Erscheinen von Ordnung aus dem Chaos eher die Regel als die Ausnahme. Dieses unter dem Begriff Selbstorganisation oder Synergetik bekannte Phänomen findet bereits seit längerem Anwendung in der Physik, Chemie, Biologie, Mathematik, Soziologie und Ökologie und wird jetzt zum Verständnis psychologischer Zusammenhänge herangezogen [Schiepek et al., 1995; Tschacher, 1997; Schröer, 1998]. Die naturwissenschaftlichen Begriffe der Selbstorganisationstheorie dienen vorerst, wie auch in diesem Beitrag, der metaphorischen Betrachtung humaner psychischer und sozialer Systeme, d.h. sie sind von heuristischem Wert und regen die Konzeptbildung an. Freud und Jung liessen sich bekanntlich ebenfalls sehr durch die Physik und ihre Nachbarwissenschaften inspirieren.
4-Aminopyridine in Scala media Reversibly Alters the Cochlear Potentials and Suppresses Electrically Evoked Oto-Acoustic Emissions
Authors: Kirk Desmond L. , Yates Graeme K.
Published: April 2003

Iontophoresis of 4-aminopyridine into scala media of the guinea pig cochlea caused elevation of the thresholds of the compound action potential of the auditory nerve, loss of amplitude of the extracellular cochlear microphonic response (CM), increase in the endocochlear potential (EP) and reduction in the amplitude of electrically evoked oto-acoustic emissions (EEOAEs). These changes were reversible over 10–20 min. The reciprocity of the changes in the CM and the EP was consistent with an interruption of both DC and AC currents through outer hair cells (OHCs), probably by blockade of mechano-electrical transduction (MET) channels in OHCs. Reductions in EEOAEs were consistent with the extrinsically applied generating current entering the OHC via the MET channels. Implications for the activation of OHC electro-motility in vivo are discussed.
A ‘Neural’ Response with 3-ms Latency Evoked by Loud Sound in Profoundly Deaf Patients
Authors: Kato Toshihiko , Shiraishi Kimio , Eura Youich , Shibata Kensuke , Sakata Toshifumi , Morizono Tetsuo , Soda Toyoji
Published: April 2003

A large negative deflection with a latency of 3 ms was observed in the auditory brainstem response (ABR) waveforms of some patients with peripheral profound deafness. This deflection was termed the N3 potential. In this paper, we review patients with the N3 potential and discuss the characteristics of abnomral ABR waveforms. The origin of the N3 potential was also discussed, especially with respect to vestibular evoked potentials. In most of the patients, audiograms showed no response to the maximum output of an audiometer in the high-frequency range and a residual response in the low-frequency range. The N3 potentials were noted at intensities of 80 dB nHL or greater. As the stimulus intensity increased, the amplitude of the potential increased and the latency decreased. A high repetition rate (83.3/s) of the click stimulus influenced the latency and amplitude of the N3 potential. The potential was replicated on retest within less than a month, and had a consistent latency and amplitude over the scalp. The results indicate that the N3 potential is not an electrical artifact but a physiological neural response evoked by a loud sound. The N3 potential is most likely not an auditory evoked response from cochlear or a response from a semicircular canal, because it has a 3-ms latency, a sharp waveform, and is unassociated with vertigo. The results suggest that the N3 potential may be a saccular acoustic response.
Three-Dimensional Reconstruction of the Auditory Cortical Areas from Magnetic Resonance Images
Authors: Steinsträter Olaf , Lütkenhöner Bernd
Published: April 2003

The future of neuromagnetic research will be highly dependent on the development of analysis procedures utilizing morphological information derived from magnetic resonance (MR) images. However, constraining the biomagnetic inverse problem by using such information may lead to serious misinterpretations if the reconstruction algorithm for the cortical surface overlooks boundaries between grey matter and cerebrospinal fluid (CSF) or artificially generates them. The purpose of this study was to check as to what extent an advanced automatic three-dimensional reconstruction procedure is able to segment the cortical structures located hidden in the Sylvian fissure (especially Heschl’s gyrus and planum temporale). The procedure consisted of four processes: a coarse segmentation, a refined segmentation of the white matter, a skeletonization of the sulci and a segmentation of the cortical surface by concurrent region growing for brain and CSF. The reconstruction result for single slices basically agrees with the impression obtained upon visual inspection of the original MR data. Photorealistic visualizations, showing a good qualitative agreement with anatomical images, suggest that the reconstructed surfaces are realistic and detailed enough to be applicable in source analyses of auditory evoked fields.
Tinnitus and Event-Related Activity of the Auditory Cortex
Authors: Hoke Ellen S. , Mühlnickel Werner , Ross Bernhard , Hoke Manfried
Published: April 2003

A neuromagnetic study in tinnitus patients and normal-hearing controls was performed with a modified contingent negative variation (CNV) paradigm. While the warning stimulus S1 was a tone burst at an intensity well above threshold, the imperative stimulus S2 was presented at a near threshold intensity because, in the majority of cases, the perceived loudness of tinnitus is very close to the threshold for a pure tone of the same frequency. Subjects had to respond to S2 by pressing a button until its offset was detected. In this case, instead of the usual sudden cut-off of the CNV after the perception of S2, a slow negative deflection develops, the post-imperative negative variation (PINV). Its initial portion probably indicates the development of a second initial CNV because the subject had to attend also to the offset of S2. The neuromagnetic data were analysed both in the time domain and in the frequency domain (short-time spectral analysis of the classical EEG bands). The time domain waveform as well as the spectrotemporal patterns of the MEG bands exhibited deviations from the normal pattern in several tinnitus subgroups, depending on the characteristics of tinnitus (tonal vs. noisiform, monaural vs. binaural) and on the stimulation conditions (tinnitus side vs. non-tinnitus side).
The Binaural Interaction Component in Human ABR Is Stable within the 0- to 1-ms Range of Interaural Time Differences
Authors: Brantberg Krister , Hansson Henrik , Fransson Per-Anders , Rosenhall Ulf
Published: April 2003

The effect of unilaterally delayed acoustic stimuli on binaural interaction was studied in 12 subjects with normal hearing. Auditory brainstem response (ABR) was obtained in the midline between the forehead and the neck, and click stimuli were unilaterally delayed at 0.2-ms intervals in the 0- to 1-ms range. Binaural interaction was evaluated by measuring the β wave in the binaural difference waveform, i.e. the remainder after subtracting the binaurally evoked registration from the sum of the two monaural registrations. Computation of the binaural difference waveform showed the β wave amplitude to be relatively stable throughout the 0- to 1-ms range of interaural time differences. This finding suggests stable binaural interaction within the range of interaural time differences where binaural click stimuli induce a binaurally fused intracranial image.
A Study of Tea Tree Oil Ototoxicity
Authors: Zhang Si Yi , Robertson Donald
Published: April 2003

Tea tree oil shows promise as an effective treatment for a number of micro-organisms commonly associated with otitis externa and otitis media, but its possible ototoxicity has not been previously assessed. The ototoxicity of tea tree oil was examined in the guinea pig by measuring the thresholds of the compound auditory nerve action potential (CAP) to tone bursts before and after instillation of the oil into the middle ear. After 30 min of instillation, 100% tea tree oil caused a partial CAP threshold elevation at 20 kHz. A lower concentration of oil [2% tea tree oil dissolved in saline using 0.5% detergent (Tween-80)] did not cause any significant lasting threshold change after middle ear instillation for the same period of time. The latter concentration of oil is greater than the minimum inhibitory concentration reported for most micro-organisms in the effective spectrum of the oil and this suggests that this concentration may be safe and effective provided only short exposures (about 30 min) are used. The results suggest that high concentrations of tea tree oil applied to the round window for a relatively short time are to some extent ototoxic to the high-frequency region of the cochlea. Hence further study is needed to establish whether tea tree oil can be used with safety in the treatment of external and middle ear infections.
Progressive Deterioration of Central Components of Auditory Brainstem Responses during Postnatal Development of the Myelin Mutant taiep Rat
Authors: Roncagliolo Manuel , Benítez Juana , Eguibar José R.
Published: April 2003

Auditory brainstem responses (ABRs) were evaluated during the postnatal development (P10–P180) of taiep rats, neurological mutants characterized by early abnormal myelin development and subsequent demyelination of the CNS. The disorder is produced by an autosomal recessive mutation trait that affects the oligodendrocytes but not the Schwann cells. After onset of ABRs (P12–P14), taiep rats and their nonaffected heterozygous littermates that served as controls showed a similar pattern of maturation for wave I. The central waves (In–IV) showed significantly longer latencies in the mutants. By P60–P180, the later waves (III and IV) were frequently difficult to discern. From the onset of ABRs, the interpeak latency I–IV, corresponding to the central conduction time (CCT) of the auditory pathway, showed in taiep rats significantly longer values than controls. After an initial reduction, proportional to that of control rats, the CCT value increased progressively during the second month of the mutants’ lives. The electrophysiological results of the present study strongly support the hypothesis that mutation in the taiep rat impairs neuromaturation of the central auditory pathway in the brainstem by affecting the myelination process in the CNS.
Human Frequency-Following Response: Representation of Tonal Sweeps
Authors: Krishnan Ananthanarayan , Parkinson Jeff
Published: April 2003

Auditory nerve single-unit population studies have demonstrated that phase locking plays a dominant role in the neural encoding of steady-state speech sounds. Recently, we have reported that the phase-locked activity underlying the human frequency-following response (FFR) could also encode the first two formants of several tonal approximations of steady-state vowels. Since auditory nerve single-unit population studies have also demonstrated that phase locking is used to represent time-varying speech-like sounds, it was reasoned that the phase-locked neural activity underlying the human FFR, likewise, is dynamic enough to represent time-varying sounds. FFRs to a rising and a falling tone were obtained from 8 normal-hearing adults at 95, 85, 75 and 65 dB nHL. Results clearly demonstrated that the human FFR does indeed follow the trajectory of the rising and falling tones. Also, amplitude changes in the FFR supported the view that neural phase locking decreases with increasing frequency. Finally, the relatively smaller FFR amplitude for the falling tone compared to its rising counterpart lends further support to the notion that rising tones produce greater neural synchrony than falling tones. These results indicate that the human FFR may be used to evaluate encoding of time-varying speech sounds like diphthongs and certain consonant-vowel syllables.
Trace Elements in Hemodialysis and Continuous Ambulatory Peritoneal Dialysis Patients
Authors: Zima Tomáš , Mestek Oto , Němeček Karel , Bártová Veronika , Fialová Jana , Tesař Vladimír , Suchánek Miloslav
Published: April 2003

Alterations in blood and tissue concentrations of trace elements in patients with chronic renal failure have been extensively investigated. Selenium, zinc and copper are elements which play an important role in biological systems as components of proteins, enzymes and antioxidants. The concentrations of selenium, zinc and copper were determined in the plasma, erythrocytes and whole blood of patients on regular hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) treatment using the method of inductively coupled plasma mass spectrometry (ICP-MS). Analysis of isotopes 77Se, 66Zn and 65Cu was performed. Methodology presents the major limitation to valid studies on trace element levels in biological materials. One of the widely used contemporary techniques is ICP-MS. It is the most sensitive one and has a high dynamic range. The selenium concentration in the studied compartments (plasma 46.1 ± 3.0 vs. 78.0 ± 3.4 μg/l, p < 0.001; erythrocytes 90.4 ± 6.5 vs. 134.2 ± 7.6 μg/l, p < 0.01; whole blood 67.3 ± 3.1 vs. 106.4 ± 3.4 μg/l, p < 0.001) was significantly lower in HD patients compared to healthy controls. The same result was observed in plasma (63.2 ± 5.8 vs. 78.0 ± 3.4 μg/l, p < 0.05) and whole blood (82.7 ± 7.4 vs. 106.4 ± 3.4 μg/l, p < 0.01) from CAPD patients, but the selenium level of erythrocytes in CAPD patients was the same as in the control group (126.0 ± 8.8 vs. 134.2 ± 7.6 μg/l). The cooper content of erythrocytes was lower in HD patients than in controls (0.55 ± 0.02 vs. 0.66 ± 0.01 mg/l, p < 0.01) and CAPD groups (0.55 ± 0.02 vs. 0.68 ± 0.02 mg/l, p < 0.001). There were no differences in copper content in plasma (HD 1.02 ± 0.06; CAPD 1.11 ± 0.09; controls 1.02 ± 0.05  mg/l) and whole blood (HD 0.87 ± 0.04; CAPD 0.90 ± 0.05; controls 0.85 ± 0.02 mg/l) in HD and CAPD patients and healthy controls. The zinc concentration was increased in the whole blood of CAPD patients (6.68 ± 0.36 vs. 5.52 ± 0.11 mg/l, p < 0.001) and erythrocytes of HD (12.30 ± 0.23 vs. 10.11 ± 0.42 mg/l, p < 0.001), and CAPD groups (13.71 ± 0.56 vs. 10.11 ± 0.42 mg/l, p < 0.001) compared to controls. However, the plasma zinc concentration was lower in HD patients compared to blood donors (0.69 ± 0.03 vs. 0.92 ± 0.03 mg/l, p < 0.001) and CAPD patients (0.69 ± 0.03 vs. 0.95 ± 0.04 mg/l, p < 0.001). We did not find a significant increase in trace elements in whole blood after HD. These results suggest differences between plasma, erythrocytes and whole blood concentrations of the studied trace elements. The levels of trace elements are altered by HD and CAPD. A modern precise method with high accuracy, ICP-MS, which was used in our study, eliminated analytical errors and possible interferences.
Increase in Resting Levels of Superoxide Anion in the Whole Blood of Uremic Patients on Chronic Hemodialysis
Authors: Chen Ming-Feng , Chang Chi-Lin , Liou Shaw-Yih
Published: April 2003

Recently, we developed a new method to measure the resting level of superoxide anion in whole blood using an ultrasensitive chemiluminescence analyzer and lucigenin amplification. The advantage of this method is that the assay system can be performed in the absence of leukocyte isolation and stimulant administration. In this study, we applied this method to measure the blood resting levels of superoxide anion in 104 uremic patients on chronic hemodialysis (CHD) and 98 sex- and age-matched healthy controls to clarify the influence of HD on blood levels of superoxide anion. Simultaneously, the plasma levels of copper, zinc superoxide dismutase (Cu,Zn-SOD), glutathion peroxidase (GPX), myeloperoxidase (MPO) and lactoferrin (Lacto-F) were measured. The results showed that the basal blood levels of superoxide anion, Cu,Zn-SOD, and MPO in CHD patients were significantly greater than those of healthy controls. However, there was no difference in the basal plasma levels of Lacto-F and GPX between CHD patients and healthy controls. One session of HD further increased the blood levels of superoxide anion, MPO, Lacto-F and Cu,Zn-SOD but not GPX. These results suggest that the blood levels of superoxide anion are higher in CHD patients and further increase after one session of HD. This mechanism should be studied further.
Surface Antigen Expression and Platelet Neutrophil Interactions in Haemodialysis
Authors: Bonomini M. , Sirolli V. , Settefrati N. , Stuard S. , Tropea F. , Di Liberato L. , Tetta C. , Albertazzi A.
Published: April 2003

Background: There is increasing evidence to show the clinical implications of membrane biocompatibility in haemodialysis therapy. Methods: We conducted a cross-over clinical study examining the clinical biocompatibility profile of three derivatised cellulosic membranes obtained by means of different modifications to the cellulose polymer (haemophan, cellulose diacetate, benzyl cellulose) in comparison to the parent polymer (cuprophan) and a reference synthetic membrane (polysulfone). Results: In terms of leukopenia production, derivatised cellulosic membranes were generally intermediate between cuprophan and polysulfone, haemophan being more marked than the other two membranes. Upregulation of CD11b/CD18 molecule on neutrophils was found with all membranes, to a greater extent with the dialyser containing cuprophan. The expression of CD11b/CD18 on monocytes was slightly affected with cuprophan only. The neutrophil and monocyte counts throughout the entire dialysis session showed a much better correlation with the cellular expression of sialyl-Lewis x (CD15s) molecule than with CD11b/CD18 expression. An increased formation of platelet-neutrophil coaggregates occurred at 15 and 30 min during dialysis with all membranes but benzyl cellulose, the increase with cuprophan being higher than with the other membranes. In concomitance with the increase in platelet-neutrophil coaggregation, an increased hydrogen peroxide production by neutrophils occurred, which proved to be significantly higher compared to the unchanged neutrophil hydrogen peroxide production during HD with benzyl cellulose. Conclusions: Our results demonstrate that derivatised cellulose is associated with a considerable improvement in the clinical biocompatibility profile. Derivatised cellulosic membranes show many similarities but also several significant differences which very likely stem from the different type of structural modification to the cellulose polymer rather than from the degree of hydroxyl group replacement.
Oxidative Modification of Low-Density Lipoprotein (LDL) in HD Patients: Role in Electronegative LDL Formation
Authors: Ziouzenkova Ouliana , Sevanian Alex
Published: April 2003

High cardiovascular mortality in patients on hemodialysis (HD) is largely attributed to oxidative stress and altered lipoprotein profiles. Markedly increased levels of mildly modified LDL subfractions, such as dense LDL and electronegatively charged LDL (LDL–), are present in the blood of HD patients and may be markers of atherosclerosis risk. LDL–, characterized by modified protein content and elevated levels of lipid peroxidation products, is representative of multiple oxidative processes acting on plasma lipoproteins that prevail during HD. In this review, we discussed known mechanisms leading to that may account for oxidative protein modification and/or LDL– formation in the context of specific conditions associated with HD.
Association of a redefined proximal mouse chromosome 11 imprinting region and U2afbp-rs/U2af1-rs1 expression
Authors: Cattanach B.M. , Shibata H. , Hayashizaki Y. , Townsend K.M.S. , Ball S. , Beechey C.V.
Published: April 2003

Mice with maternal and paternal disomy for chromosome 11 (Chr 11) show growth retarded and overgrowth phenotypes, respectively, which can be attributed to genomic imprinting. Previous studies have defined the region of Chr 11 responsible (the Chr 11 imprinting region) as lying proximal to the T30H translocation breakpoint at the borders of G-bands 11B1.2 and 11B1.3. Evidence is presented here with two new translocations, T57H and T41Ad, which sequentially reduce the size of the imprinting region and locate it proximal to the T41Ad breakpoint in G-band 11A3.2. It therefore lies close to the centromere. The imprinted gene, U2af1-rs1, is known to be located within the original region and has been regarded as a candidate for the imprinting effects. Meiotic and mitotic chromosome FISH analysis, together with U2af1-rs1 expression studies are now described which show that the gene lies within the newly defined imprinting region and that its expression levels relate to the presence/absence and number of functional paternal alleles. U2af1-rs1 therefore remains a candidate gene for the Chr 11 imprinting effects. However, another recently reported imprinted gene, Meg1/Grb10, that lies within the region is also a good candidate, as it encodes a growth factor receptor. Meg1/Grb10 maps about 15 cM from U2af1-rs1 and is separated by conserved regions showing homology with two different human chromosomes. For these reasons, and because the two human homologues of U2af1-rs1 and Meg1/Grb10 also lie on different chromosomes, it would seem likely that the two genes identify two distinct imprinting domains within the small proximal region of mouse Chr 11.
On GATAGATA and other “junk” in the barren stretch of genomic desert
Authors: Epplen J.T. , Mäueler W. , Santos E.J.M.
Published: April 2003

(GATA)n and additional simple repeated DNA sequences have long been known but functional analyses along traditional research strategies have not yielded definitive results. Therefore these elements are commonly regarded as genomic “junk” although they represent assets for innovative methodological approaches and especially for speculations. While extensively using microsatellites for genome mapping and genetic relationship analyses, it was also realized that certain simple repeats can cause human trinucleotide block expansion diseases. Hence these simple repeat elements comprise an exceptional range of biological meaning, i.e. from genetically absolutely neutral markers for genome analysis, behavioral and population genetic studies to dominant and invariably disease causing mutations with complete penetrance. The quest into why there is so much repetitive junk in recent genomes can be answered only in part and sequentially, but sometimes – even after substantial efforts – not for the given element.
Comparative FISH mapping of mouse and rat homologues of twenty-five human X-linked genes
Authors: Kuroiwa, A. , Watanabe, T. , Hishigaki, H. , Takahashi, E. , Namikawa T. , Matsuda Y.
Published: April 2003

We constructed a comparative cytogenetic map of 25 functional genes in mouse and rat X chromosomes by direct R-banding fluorescence in situ hybridization. Nineteen and 22 out of the 25 genes, which have been mapped on the human X chromosome, were newly localized to mouse and rat X chromosomes, respectively. Twenty-two additional genes were integrated in the rat-mouse-human comparative map of the X chromosome in this study. Comparison of the gene order indicated the presence of four chromosome segments with conserved linkage homology between mouse and rat X chromosomes, suggesting that a minimum of four chromosomal inversion events occurred between mouse and rat X chromosomes during the evolution of the two species. Four chromosome segments with conserved linkage homology were found between human and rat X chromosomes.
Cytogenetic localization of cancer-related genes in the rat and comparative mapping studies in human and mouse
Authors: Johansson Å. , Helou K. , Levan G.
Published: April 2003

The rat is an important model organism in biomedical research, and several well-characterized rat cancer model systems exist. To facilitate detailed analysis of these models, it is useful to know the regional location of known cancer-related genes. In this report, 14 cancer-related genes have been sublocalized by fluorescence in situ hybridization. The mapped genes include three oncogenes (Fyn, Mas1, and Vav1), a tyrosine kinase gene (Syk), a tumor-associated antigen gene (Cd24), a growth factor receptor gene (Igf2r), the gene for an activator of c-fos/c-jun transcription factors (Apex), a transcription factor gene (Egr3), and several genes involved in steroid hormone metabolism and signaling (Esr2, Pgr, Cbg, Cyp17, and Cyp19). The remaining gene (Map1a) is involved in microtubule assembly.
Baboon/human homologies examined by spectral karyotyping (SKY): a visual comparison
Authors: Best R.G. , Diamond D. , Crawford E. , Grass F.S. , Janish C. , Lear T.L. , Soenksen D. , Szalay A.A. , Moore C.M.
Published: April 2003

Baboon (Papio hamadryas) metaphase chromosomes were analyzed using spectral karyotyping (SKY), a technique combining fluorescence microscopy, CCD-imaging, and Fourier spectroscopy. Results from a comparison of SKY analyses using probes derived from human chromosomes on baboon metaphases were consistent with the majority of comparative gene mapping data between the two species. These data were also compatible with earlier studies comparing macaque and human chromosomes. Human (HSA) chromosome 2 was homologous to baboon (PHA) chromosomes 12 (HSA 2q) and 13 (HSA 2p), whereas three baboon chromosomes corresponded to two different human chromosomes: PHA 3 to HSA 7 and HSA 21, PHA 7 to HSA 14 and HSA 15, and PHA 10 to HSA 20 and HSA 22. These results support the retained synteny between the Hominidae and Cercopithecidae genomes.
Refined physical mapping and genomic structure of the EXTL1 gene
Authors: Wuyts W. , Spieker N. , van Roy N. , De Boulle K. , De Paepe A. , Willems P.J. , van Hul W. , Versteeg R. , Speleman F.
Published: April 2003

Recently, the EXTL1 gene, a member of the EXT tumor suppressor gene family, has been mapped to 1p36, a chromosome region which is frequently implicated in a wide variety of malignancies, including breast carcinoma, colorectal cancer and neuroblastoma. In this study, we show that the EXTL1 gene is located between the genetic markers D1S511 and D1S234 within 200 kb of the LAP18 gene on chromosome 1p36.1, a region which has been proposed to harbor a tumor suppressor gene implicated in MYCN-amplified neuroblastomas. In addition, we determined the genomic structure of the EXTL1 gene, revealing that the EXTL1 coding sequence spans 11 exons within a 50-kb region.
TBL2, a novel transducin family member in the WBS deletion: characterization of the complete sequence, genomic structure, transcriptional variants and the mouse ortholog
Authors: Pérez Jurado L.A. , Wang Y.-K. , Francke U. , Cruces J.
Published: April 2003

Williams-Beuren syndrome (WBS) is a developmental disorder with multi-system manifestations caused by haploinsufficiency for contiguous genes deleted in chromosome region 7q11.23. The size of the deletion is similar in most patients due to a genomic duplication that predisposes to unequal meiotic crossover events. While hemizygosity at the elastin locus is responsible for the cardiovascular features, the contribution of other genes to the WBS phenotype remains to be demonstrated. We have identified a novel gene, TBL2, in the common WBS deletion. TBL2 is expressed as a 2.4-kb transcript predominantly in testis, skeletal muscle, heart and some endocrine tissues, with a larger ∼5-kb transcript detected ubiquitously at lower levels. TBL2 encodes a protein with four putative WD40-repeats. An alternatively spliced transcript in TBL2 introduces a novel second exon with an in frame stop codon. This mRNA encodes a 75 amino acid protein with 43 amino acids identical to TBL2 at the N-terminus and no known functional domain. The mouse homolog, Tbl2, shows 84% sequence identity at the nucleotide level and 92% similarity at the amino acid level. Comparison of the mouse and human sequences identifies a conserved region that extends upstream of the previously published sequence with an initiation codon common to both species that adds 21 amino acids at the N-terminus. The Tbl2 gene has been mapped to mouse chromosome 5 in a region of conserved synteny with human 7q11.23. Since haploinsufficiency has been shown for other WD-repeat containing proteins, hemizygosity of TBL2 may contribute to some of the aspects of the complex WBS phenotype.
Interphase FISH for rapid identification of a Down syndrome animal model
Authors: Strovel J. , Stamberg J. , Yarowsky P.J.
Published: April 2003

Mouse models of Down syndrome (trisomy 21, DS) have been developed to study the consequences of triplication of regions syntenic to distal human chromosome 21. We report a technique for the identification of segmental trisomy 16 (Ts65Dn) and diploid progeny at any age using interphase fluorescence in situ hybridization (FISH) of uncultured tail fibroblasts. Our technique is faster and less expensive than blood karyotyping.
Zoo-FISH analysis of dog chromosome 5: identification of conserved synteny with human and cat chromosomes
Authors: Thomas R. , Breen M. , Langford C.F. , Binns M.M.
Published: April 2003

Conserved segments of synteny between the human genome and chromosome 5 (CFA 5) of the domestic dog (Canis familiaris) have been identified by reciprocal chromosome painting analysis. A CFA 5 paint probe was applied to human metaphase spreads, revealing distinct hybridisation sites on human (HSA) chromosomes 1, 11, 16, and 17. Paint probes for these human chromosomes were then hybridised to dog metaphase spreads, identifying the regions of CFA 5 with which homology is shared with the corresponding human chromosome. Application of the CFA 5 paint probe to metaphase spreads of the domestic cat (Felis catus, FCA) demonstrated hybridisation to cat chromosomes C1, D1, E1, and E2. Dog PCR primers for type 1 markers known to lie in the corresponding regions of HSA 11, 16, and 17 were used to isolate dog BAC clones representing four genes. Fluorescence in situ hybridisation analysis confirmed their localisation to CFA 5 and suggested that two of the conserved segments lie in opposing orientations on CFA 5, compared to the human chromosome concerned. A third segment appears to lie in the same orientation on both human and dog chromosomes. No suitable gene markers were available for analysis of the fourth segment. The significance of these findings is discussed with reference to current and future dog genome mapping efforts.
Cooperation of selection and meiotic mechanisms in the production of imbalances in reciprocal translocations
Authors: Faraut T. , Mermet M.-A. , Demongeot J. , Cohen O.
Published: April 2003

We have used data from chromosomally unbalanced offspring observed at birth, as well as data from sperm chromosome analysis, to study the meiotic segregation of reciprocal translocations. Using data from a total of 1,597 unbalanced children, we have observed an excess in maternal origin for all modes of imbalance. This excess is particularly marked for the 3:1 unbalanced mode, for which we have also observed a maternal age effect, indicating a close relationship with autosomal trisomies. In addition, a statistical analysis of data from 34 different published studies using sperm chromosome analysis has demonstrated that factors which, for reasons of viability, produce a predisposition for a particular mode of imbalance at birth also appear to favor meiotic production of this type of imbalance. Thus the production of unbalanced gametes of a particular type is influenced by the size of the imbalance.
Cloning and expression of CIS6, chromosome assignment to 3p22 and 2p21 by in situ hybridization
Authors: Magrangeas F. , Apiou F. , Denis S. , Weidle U. , Jacques Y. , Minvielle S.
Published: April 2003

A family of negative regulators of JAK signaling pathway referred to as suppressor of cytokines signaling (SOCS) or cytokine-inducible SH2 protein (CIS) has been recently identified. In order to find additional members of this family, we have used a consensus amino acid sequence contained in the well-conserved central SH2 domain to search DNA databases. We isolated cDNA coding for the human homologue of SOCS-5, referred to as CIS6. Northern blot analysis revealed CIS6 mRNA expression in various tissues such as heart, muscle, spleen, and thymus and in all myeloma cell lines examined. The gene was assigned to human chromosome bands 2p21 and 3p22 by in situ hybridization. CIS6 is structurally related to other members of the CIS family and therefore could act as a negative regulator of signal transduction.
Cloning, genomic sequence, and chromosome mapping of Scyb11, the murine homologue of SCYB11 (alias βR1/H174/SCYB9B/I-TAC/IP-9/CXCL11)
Authors: Meyer M. , Erdel M. , Duba H.C. , Werner E.R. , Werner-Felmayer G.
Published: April 2003

A T-cell attracting CXC chemokine phylogenetically related to MIG and SCYB10 was recently characterized and termed SCYB11 (alias βR1/H174/SCYB9B/I-TAC/IP-9/CXCL11). Here, we cloned the cDNA of the murine homologue of this protein, Scyb11, from interferon-γ/lipopolysaccharide-stimulated RAW264.7 mouse macrophage-like cells. The nucleotide sequence of Scyb11 shares 63% identity with its human counterpart. It encodes a 100 amino acid immature protein of 11,265 Da which contains a putative signal peptide of 21 amino acids. The molecular mass of the mature protein was calculated to be 9,113 Da. Sequence identity of the murine and human SCYB11 proteins is 68%. Phylogenetic tree analysis of mouse CXC chemokines places SCYB11 together with the murine homologues of MIG and SCYB10 (Crg-2/muIP-10) on an individual branch. A genomic sequence was obtained by genome walking and subcloning DNA fragments from a BAC clone containing Scyb11. Like human SCYB11, Scyb11 contains 4 exons with intron/exon boundaries at positions comparable to the human gene. Whereas introns 2 and 3 are of similar length in the murine and human genes, intron 1 of Scyb11 contains 1,260 bp more than intron 1 of the human gene. Intron 1 of Scyb11 is also characterized by a 201-bp stretch with repetitive sequences of high cryptic simplicity. Using a BAC clone containing Scyb11, this gene could be mapped to chromosome 5 at position 5E3. Since human SCYB11 is localized on 4q21.2, this result confirms the mouse/human homology of the two chromosome regions.