bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of the baroreceptor reflex by the dorsomedial hypothalamic nucleus and perifornical area
Authors: McDowall Lachlan M. , Horiuchi Jouji , Killinger Suzanne , Dampney Roger A. L.
Published: November 2005

Neurons within the dorsomedial hypothalamic nucleus (DMH) and perifornical area (PeF), which lie within the classic hypothalamic defense area, subserve the cardiovascular response to psychological stress. Previous studies have shown that electrical stimulation of the hypothalamic defense area causes inhibition of the cardiac and (in some cases) sympathetic components of the baroreceptor reflex. In contrast, naturally evoked psychological stress does not appear to be associated with such inhibition. In this study, we tested the effect of specific activation of neurons within the DMH and PeF on the baroreflex control of renal sympathetic nerve activity and heart rate in urethane-anesthetized rats. Microinjection of bicuculline (a GABAAreceptor antagonist) into the DMH caused dose-dependent increases in heart rate and renal sympathetic activity, shifted the baroreflex control of both variables to higher levels (i.e., increased the upper and lower plateaus of the baroreflex function curves, and increased the threshold, midpoint, and saturation levels of mean arterial pressure). The maximum gain of the sympathetic component of the baroreflex was also increased, while that of the cardiac component was not significantly changed. Increases in the midpoint were very similar in magnitude to the evoked increases in baseline mean arterial pressure. Microinjection of bicuculline into the PeF evoked very similar effects. The results indicate that disinhibition of neurons in the DMH/PeF region not only increases sympathetic vasomotor activity and heart rate but also resets the baroreceptor reflex such that it remains effective, without any decrease in sensitivity, over a higher operating range of arterial pressure.
Differential regulation of suppressor of cytokine signaling-3 in the liver and adipose tissue of the sheep fetus in late gestation
Authors: Gentili Sheridan , Waters Michael J. , McMillen I. Caroline
Published: November 2005

It is unknown whether the JAK/STAT/suppressor of cytokine signaling-3 (SOCS-3) intracellular signaling pathway plays a role in tissue growth and metabolism during fetal life. We investigated whether there is a differential profile of SOCS-3 expression in the liver and perirenal adipose tissue during the period of increased fetal growth in late gestation and the impact of fetal growth restriction on SOCS-3 expression in the fetal liver. We also determined whether basal SOCS-3 expression in the fetal liver and perirenal adipose tissue is regulated by endogenous fetal prolactin (PRL). SOCS-3 mRNA abundance was higher in the liver than in the pancreas, spleen, and kidney of the sheep fetus during late gestation. In the liver, SOCS-3 mRNA expression was increased ( P < 0.05) between 125 ( n = 4) and 145 days ( n = 7) gestation and lower ( P < 0.05) in growth-restricted compared with normally grown fetal sheep in late gestation. The relative expression of SOCS-3 mRNA in the fetal liver was directly related to the mean plasma PRL concentrations during a 48-h infusion of either a dopaminergic agonist, bromocriptine ( n = 7), or saline ( n = 5), such that SOCS-3 mRNA expression was lower when plasma PRL concentrations decreased below ∼20 ng/ml [ y = 0.99 − (2.47/ x) + (4.96/ x2); r2 = 0.91, P < 0.0001, n = 12]. No relationship was shown between the abundance of phospho-STAT5 in the fetal liver and circulating PRL. SOCS-3 expression in perirenal adipose tissue decreased ( P < 0001) between 90–91 ( n = 6) and 140–145 days ( n = 9) gestation and was not related to endogenous PRL concentrations. Thus SOCS-3 is differentially expressed and regulated in key fetal tissues and may play an important and tissue-specific role in the regulation of cellular proliferation and differentiation before birth.
No effect of short-term 17β-estradiol supplementation in healthy men on systemic inflammatory responses to exercise
Authors: Timmons Brian W. , Hamadeh Mazen J. , Tarnopolsky Mark A.
Published: November 2005

Sex-based differences in inflammatory responses to exercise may be mediated by estrogen through increased muscle membrane stability and/or inhibited cytokine production. In this study, in vivo effects of estrogen on systemic inflammation-related responses to exercise were assessed in healthy men. In a double-blind, placebo-controlled, crossover design, 11 men cycled for 90 min at 65% V̇o2 maxafter 8 days of 17β-estradiol supplementation (ES; 2 mg/day) or placebo (PL; glucose polymer). After a 2-wk washout, exercise was repeated after 8 days on the alternate treatment. Blood was collected pre- and postexercise to determine IL-6, soluble intercellular adhesion molecule-1 (sICAM-1), neutrophil counts, and cortisol. Preexercise serum was assayed for sex hormones. ES increased estradiol (133 ± 71 to 840 ± 633 pmol/l, P = 0.005) and reduced testosterone (19.9 ± 3.7 to 16.1 ± 3.9 nmol/l, P = 0.007). Exercise increased cortisol ( P = 0.02), IL-6 ( P < 0.001) and neutrophil counts ( P < 0.001) with no influence on sICAM-1 ( P = 0.34) and no effect of ES on these changes. Postexercise IL-6 and neutrophil counts were correlated ( r = 0.58, P = 0.005); postexercise IL-6 and cortisol ( r = 0.18, P = 0.43) and postexercise cortisol and neutrophil counts ( r = 0.06, P = 0.78) were not. Postexercise sICAM-1 was not correlated with the above variables ( P ≥ 0.79). In conclusion, 8 days of ES in healthy men did not influence systemic inflammation-related responses to acute exercise. Future studies should investigate 17β-estradiol effects on IL-6 production and neutrophil infiltration within skeletal muscle during and after exercise.
Differential changes in muscle oxygenation between voluntary and stimulated isometric fatigue of human dorsiflexors
Authors: McNeil Chris J. , Murray Brad J. , Rice Charles L.
Published: November 2005

The purpose of this study was to compare fatigue and recovery of maximal voluntary torque [maximal voluntary contraction (MVC)] and muscle oxygenation after voluntary (Vol) and electrically stimulated (ES) protocols of equal torque production. On 1 day, 10 male subjects [25 yr (SD 4)] completed a Vol fatigue protocol and, on a separate day, an ES fatigue protocol of the right dorsiflexors. Each task involved 2 min of intermittent (2-s on, 1-s off) isometric contractions at 50% of MVC. For the ES protocol, stimulation was delivered percutaneously to the common peroneal nerve at a frequency of 25 Hz. Compared with the Vol protocol, the ES protocol caused a greater impairment in MVC (75 vs. 83% prefatigue value; Pre) and greater increase in 50-Hz half relaxation time (165 vs. 117% Pre) postexercise. After acute (1 min) recovery, MVC impairment was similar for both protocols, whereas 50- Hz half relaxation time was still greater in the ES than Vol protocol. Total hemoglobin decreased to a similar extent in both protocols during exercise, but it was elevated above the resting value to a significantly greater extent for the ES protocol in recovery (18 vs. 11 μM). Oxygen saturation was significantly lower in the ES than Vol protocol during exercise (46 vs. 57% Pre), but it was significantly greater during recovery (120 vs. 105% Pre). These findings suggest that despite, equal torque production, ES contractions impose a greater metabolic demand on the muscle that leads to a transient greater impairment in MVC. The enforced synchronization and fixed frequency of excitation inherent to ES are the most likely causes for the exacerbated changes in the ES compared with the Vol protocol.
Hindlimb unloading increases muscle content of cytosolic but not nuclear Id2 and p53 proteins in young adult and aged rats
Authors: Siu Parco M. , Pistilli Emidio E. , Murlasits Zsolt , Alway Stephen E.
Published: November 2005

This study tested the hypothesis that inhibitor of differentiation-2 (Id2), p53, and heat shock proteins (HSP) are responsive to suspension-induced muscle atrophy. Fourteen days of hindlimb suspension were used to unload the hindlimbs and induce atrophy in gastrocnemius muscles of young adult and aged rats. Following suspension, medial gastrocnemius muscle wet weight was reduced by ∼30%, and the muscle wet weight normalized to the animal body weight decreased by 11 and 15% in young adult and aged animals, respectively. mRNA abundances of Id2, p53, HSP70–2, and HSP27 did not change with suspension, whereas HSP70–1 mRNA content was lower in the suspended muscle compared with the control muscle in both young adult and aged animals. Our immunoblot analyses indicated that protein expressions of HSP70 and HSP60 were not different between suspended and control muscles in both ages, whereas HSP27 protein content was increased in suspended muscle relative to control muscle only in young adult animals. Id2 and p53 protein contents were elevated in the cytosolic fraction of suspended muscle compared with the control muscle in both young and aged animals, but these changes were not found in the nuclear protein fraction. Furthermore, compared with young adult, aged muscles had a lower HSP70–1 mRNA content but higher HSP70–2 mRNA content and protein contents of Id2, p53, HSP70, and HSP27. These findings are consistent with the hypothesis that Id2 and p53 are responsive to unloading-induced muscle atrophy. Moreover, our data indicate that aging is accompanied with altered abundances of HSP70–1 and HSP70–2 mRNA, in addition to Id2, p53, HSP70, and HSP27 protein in rat gastrocnemius muscle.
Both Hypomethylation and Hypermethylation in a 0.2-kb Region of a DNA Repeat in Cancer
Authors: Nishiyama Rie , Qi Lixin , Lacey Michelle , Ehrlich Melanie
Published: November 2005

NBL2 is a tandem 1.4-kb DNA repeat, whose hypomethylation in hepatocellular carcinomas was shown previously to be an independent predictor of disease progression. Here, we examined methylation of all cytosine residues in a 0.2-kb subregion of NBL2 in ovarian carcinomas, Wilms' tumors, and diverse control tissues by hairpin-bisulfite PCR. This new genomic sequencing method detects 5-methylcytosine on covalently linked complementary strands of a DNA fragment. All DNA clones from normal somatic tissues displayed symmetrical methylation at seven CpG positions and no methylation or only hemimethylation at two others. Unexpectedly, 56% of cancer DNA clones had decreased methylation at some normally methylated CpG sites as well as increased methylation at one or both of the normally unmethylated sites. All 146 DNA clones from 10 cancers could be distinguished from all 91 somatic control clones by assessing methylation changes at three of these CpG sites. The special involvement of DNA methyltransferase 3B in NBL2 methylation was indicated by analysis of cells from immunodeficiency, centromeric region instability, and facial anomalies syndrome patients who have mutations in the gene encoding DNA methyltransferase 3B. Blot hybridization of 33 cancer DNAs digested with CpG methylation-sensitive enzymes confirmed that NBL2 arrays are unusually susceptible to cancer-linked hypermethylation and hypomethylation, consistent with our novel genomic sequencing findings. The combined Southern blot and genomic sequencing data indicate that some of the cancer-linked alterations in CpG methylation are occurring with considerable sequence specificity. NBL2 is an attractive candidate for an epigenetic cancer marker and for elucidating the nature of epigenetic changes in cancer.
Human Hearing Modelling Real-Time Spectrography for Visual Feedback in Singing Training
Authors: Howard David M.
Published: November 2005

The traditional form of spectrography employed for speech analysis makes use of fixed bandwidth bandpass filters, which are usually set either to wide-band or narrow-band to optimise the time and frequency resolution of the resulting spectrogram respectively. The acoustic analysis carried out by the human ear can be modelled as a bank of bandpass filters whose bandwidth changes as a function of centre frequency, and therefore the time and frequency resolution varies with frequency. This paper describes a spectrographic analysis technique that is based on peripheral human hearing and considers its potential for application within a real-time visual display for singing training by comparing its output with traditional wide- and narrow-band spectrograms. The potential advantages and disadvantages of hearing modelling spectrography for this application are illustrated and discussed for a selection of sung material, some of which has been recorded during singing lessons where traditional spectrography is being employed.
Aspirin, Warfarin and a Thienopyridine for Acute Coronary Syndromes
Authors: Konstantino Yuval , Iakobishvili Zaza , Porter Avital , Sandach Amir , Zahger Doron , Hod Hanoch , Hammerman Haim , Gottlieb Shmuel , Behar Solomon , Hasdai David
Published: November 2005

Background: Although clopidogrel and aspirin (dual therapy, DT) are used for acute coronary syndrome (ACS), sometimes treatment with warfarin (triple therapy, TT) is required. Aim: To determine the incidence, complications, and outcomes of TT. Methods: We analyzed Israeli surveys of ACS from 2000 to 2004. Results: In these surveys, 5,706 (96%) were discharged alive from hospital. Post-ACS TT and DT were 76 patients (1.3%) and 2,661 patients (46.7%), respectively. The TT group was older with more prior cardiac disease. During hospitalization, the TT patients received more intravenous anticoagulant and antithrombotic agents, and had more heart failure, arrhythmias, ischemia, and major bleeding (2.6 vs. 0.6%, p = 0.03). There were no differences in adjusted 30-day and 6-month mortality between the 2 groups. Conclusion: TT is feasible among ACS patients who require concomitant warfarin treatment.
Moderate Atheroma of the Aortic Arch and the Risk of Stroke
Authors: Tanaka Makiko , Yasaka Masahiro , Nagano Keiko , Otsubo Ryoichi , Oe Hiroshi , Naritomi Hiroaki
Published: November 2005

Background and Purpose: Severe atheroma ≧4 or 5 mm of the aortic arch is a risk factor for stroke. We investigated the most predictive characteristics of arch atheroma, including maximal plaque thickness, for subsequent cardiovascular events, and also examined whether moderate atheroma <4 mm is a risk of cerebral emboli.Methods: The maximal plaque thickness (MPT) and plaque morphologies of the aortic arch were evaluated by transesophageal echocardiography in 236 patients with ischemic stroke. We assessed the relationship between the incidence of cardiovascular events, recurrent stroke or myocardial infarction, and the characteristics of the atheroma. We also investigated the thickness of atheroma in patients with known causes of stroke (n = 148) and in patients with undetermined causes (n = 19).Results: Cardiovascular events occurred in 47 patients in the follow-up period with a mean of 3.5 years. MPT was a significant risk factor of the cardiovascular events, although plaque morphologies were not. For the receiver operator characteristics curve analysis, the suitable cutoff point of MPT associated with the cardiovascular events was 3.5 mm. Patients with MPT ≧3.5 mm had a higher risk of cardiovascular events than did those with MPT <3.5 mm. In addition, aortic atheroma with MPT ≧3.5 mm was more frequently observed in patients with undetermined causes of stroke than those with known causes at 68 vs. 39% (p = 0.024).Conclusions:MPT ≧3.5 mm is the best predictor of subsequent cardiovascular events and a possible cause of embolic stroke.
Clinical Course of Hearing and Language Development in GJB2 and Non-GJB2 Deafness following Habilitation with Hearing Aids
Authors: Matsunaga Tatsuo , Hirota Eiko , Bito Seiji , Niimi Seiji , Usami Shin-ichi
Published: November 2005

Mutations in the GJB2 gene (connexin 26) are the most common cause of nonsyndromic autosomal recessive sensorineural hearing loss. Genetic testing of GJB2 may offer opportunities to predict the features of hearing loss and prognostication of speech-language development in children with hearing loss. The present study assessed the clinical features of hearing and some aspects of language development in congenital deafness due either to GJB2 mutations or to other factors in Japanese patients who had been habilitated with hearing aids. Thirty-five unrelated subjects with nonsyndromic, congenital, bilateral sensorineural hearing loss were enrolled in the study. Among them, 16 had biallelic GJB2 mutations related to hearing loss and 17 lacked such mutations. As has been reported in populations of European ancestry, the present Japanese subjects with GJB2 mutations had a relatively high incidence of the flat pattern audiogram and nonprogressive pure tone thresholds compared with subjects without GJB2 mutations. Subjects with GJB2 mutations and those without GJB2 mutations both showed a similar tendency in speech perception, some aspects of language development, and communication methods. In both groups, development of reading ability tended to be normal, but vocabulary development tended to be delayed. The present results establish the basis for future studies to aid in the evaluation and follow-up of patients with congenital hearing loss associated with GJB2 mutations who are habilitated with hearing aids.
Assessment of Coronary Artery Disease in Hemodialysis Patients with Delayed Systolic Blood Pressure Response after Exercise Testing
Authors: Fukui Masayoshi , Mori Yasukiyo , Takehana Kazuya , Masaki Hiroya , Motohiro Masayuki , Sakamoto Norihiko , Kitamura Tetsuya , Yoshida Susumu , Nakamura Seishi , Baden Masato , Nishikawa Mitsushige , Iwasaka Toshiji
Published: November 2005

Background: We evaluated usefulness of the postexercise systolic blood pressure (SBP) response for detecting coronary artery disease (CAD) in hemodialysis patients. Methods: A treadmill exercise testing was done, and the SBP response was measured in 44 hemodialysis patients (30 men, 14 women; age 41 to 81 years). The postexercise SBP response was defined as the ratio of SBP after 3 minutes of recovery to SBP at peak exercise. Results: The SBP ratio of the 25 subjects with coronary artery stenosis (1.01 ± 0.13) was significantly greater (p <0.01) than 19 subjects without coronary artery stenosis (0.83 ± 0.10). An SBP ratio greater than 0.92 identified CAD with higher sensitivity, specificity, and accuracy than did the conventional ST-segment depression criterion (76 vs. 56%, 90 vs. 53%, and 82 vs. 55%, respectively). Conclusion: Determination of the SBP ratio is a clinically useful, noninvasive method for accurately detecting CAD in hemodialysis patients.
Regional Citrate Anticoagulation during Hemodialysis
Authors: Ridel Christophe , Mercadal Lucile , Béné Bernard , Hamani Abdelaziz , Deray Gilbert , Petitclerc Thierry
Published: November 2005

Background: Regional citrate anticoagulation during hemodialysis is promising, but its clinical implementation is routinely cumbersome because a continuous adjustment of calcium infusion at the dialyzer outlet is needed. Duocart biofiltration (DCB) is a new hemodialysis method using a calcium and magnesium-free dialysate containing only sodium chloride and bicarbonate combined with the infusion into the venous line of a solution containing the ionic complement (K, Ca, Mg) and glucose. Since the dialysate is calcium- and magnesium-free and infusion rate of the solution containing calcium is automatically determined by the dialysis delivery system according to the on-line measured value of ionic dialysance, DCB seems a technique especially suitable for citrate anticoagulation procedure. Methods: Thirty DCB sessions were performed in 10 patients with increased risk of bleeding. A commercially available mixture of trisodium citrate, citric acid and glucose was infused into the arterial line at a rate equal to 3% of dialyzer blood flow. The ionic complement (K: 48 mM, Ca: 42 mM, Mg: 14 mM, glucose: 110 mM) was infused at a rate equal to 1/24 ionic dialysance value automatically determined each 15 min by the dialysis monitor. DCB sessions were compared to 21 conventional bicarbonate hemodialysis (BHD) sessions with low-molecular-weight heparin anticoagulation. Results: Whole blood activated clotting time (WBACT) measured in the venous line (before infusion of ionic complement) was 200% of the WBACT value in the arterial line. Clotting and citrate-related adverse events were not observed. Postdialysis compression time of the arteriovenous access is significantly (p < 0.001) shorter after DCB sessions (3.9 ± 1.1 min) compared with BHD sessions (8.7 ± 4.6 min). Conclusion: Citrate anticoagulation during Duocart biofiltration is effective, safe and suitable for routine use because calcium infusion rate is automatically adjusted without the need of monitoring degree of anticoagulation and level of ionized calcium.
Biogenetic Temperament and Character and Attention Deficit Hyperactivity Disorder in Korean Children
Authors: Yoo Hee Jeong , Kim Minjeong , Ha Jee Hyun , Chung Ain , Sim Minyoung E. , Kim Seog Ju , Lyoo In Kyoon
Published: November 2005

Background: The objective of this study was to evaluate the relationship between symptoms of attention deficit hyperactivity disorder (ADHD) and biogenetic temperament, as assessed by the Junior Temperament and Character Inventory (JTCI) in Korean elementary school children. Sampling and Methods: Five hundred and sixteen elementary school students (254 boys and 262 girls; age range 9–14 years, mean age 11.0 ± 1.0 years) were studied. The Junior Temperament and Character Inventory, both the self-rating and parent rating scales, the DuPaul ADHD rating scale (ARS-IV) for parents and teachers and the Child Behavior Checklist have been completed by study subjects. Children with high ARS-IV scores (the upper 10th percentile, n = 52) were defined to have ADHD. Fifty-two age- and sex-matched non-ADHD control subjects were selected randomly from a pool of 464 subjects. Results: Inattention and hyperactivity/impulsivity symptoms correlated positively with Novelty Seeking in both children and parent ratings. These symptoms correlated negatively with Persistence, Self-Directedness and Cooperativeness. Novelty Seeking also had significant correlations with attention problems, delinquent behavior, aggressive behavior, externalizing problems and social problems in the Child Behavior Checklist. The ADHD group (n = 52) had higher scores of Novelty Seeking and lower scores of Self-Directedness and Cooperativeness, compared with the control group. Conclusions: There were significant correlations between ADHD symptoms and Novelty Seeking. Current findings suggest that Novelty Seeking and ADHD share biogenetic backgrounds.
Investigation of the Syndrome of Apotemnophilia and Course of a Cognitive-Behavioural Therapy
Authors: Braam Arjan W. , Visser Sako , Cath Daniëlle C. , Hoogendijk W.J.G.
Published: November 2005

Background: The syndrome of apotemnophilia, body integrity or amputee identity disorder, is defined as the desire for amputation of a healthy limb, and may be accompanied by behaviour of pretending to be an amputee and sometimes, but not necessarily, by sexual arousal. Sampling and Methods: A case history is presented of a 35-year-old man who was referred because of his desire for amputation of his left leg, without sexual connotations. The course of a combined cognitive behavioural psychotherapy with SSRI treatment is described. Results: Symptoms showed considerable similarity with obsessive-compulsive disorder, and some similarity with body dysmorphic disorder according to DSM-IV, but the core symptom seemed to be strongly connected with a sense of identity. Treatment with a selective serotonin re-uptake inhibitor decreased levels of distress only. The effects of cognitive restructuring of the psychotherapy were limited, whereas the behavioural elements substantially reduced the behaviour of pretending to be an amputee. Conclusions: The rare syndrome of apotemnophilia raises unresolved questions of classification. Psychotic disorders should be ruled out carefully. The model designed in the current cognitive behavioural approach may serve as a starting point for further development of intervention protocols for this rare disorder.
Vocalisation in Verbal Hallucinations: Case Report and Theoretical Model
Authors: Behrendt Ralf-Peter , Whittingham Mark
Published: November 2005

Perception of one’s speech or the speech of others reflects an intrinsic process and should not to be seen as a product of information processing of external sensory input. From this perspective, the perception of one’s own or others’ speech is fundamentally equivalent to the experience of verbal hallucinations. Speech perception is generated primarily in the focus of attention, but auditory and proprioreceptive input from verbal articulations play an important constraining role, ensuring that perception remains adaptive to interaction with the external world. In verbal hallucinations these constraints may be partially disrupted. Perceptual qualities of hallucinatory voices may be generated in the focus of attention alone (in ignorance of actual acoustic stimulation from the environment), whilst content and grammatical aspects of hallucinatory speech perception may continue to be constrained adequately by proprioreceptive reafferentation from the speech apparatus. Thus subvocal speech may play a role in the elaboration and maintenance of verbal hallucinations.
Delusions or Obsessions: The Same Only Different?
Authors: Sanders Jane , Whitty Peter , Murray Declan , Devitt Pat
Published: November 2005

The phenomenological distinction between delusions and obsessions has been the subject of much debate in psychiatry. Some authors feel these symptoms are distinct nosological entities, while others argue that they reflect manifestations of the same symptom and are distinguishable on the basis of the level of insight a patient displays. In this report we describe the case history of a lady who presented with an obsessional disorder. The symptom was resistant to standard treatments and subsequently became more delusional in nature. We review the literature in terms of the classification of obsessions and delusions and offer assistance to clinicians in terms of the diagnosis and treatment of cases where the distinction between these phenomena is not clear and offer alternative means of classifying these symptoms based on insight.
Pamidronate Therapy for Preventing Steroid-Induced Osteoporosis in Children with Nephropathy
Authors: Kim Sung-Do , Cho Byoung-Soo
Published: November 2005

Background: Steroid-induced osteoporosis (SIO) is a serious complication of long-term steroid therapy and is of particular concern in growing children. Recently bisphosphonates have been applied in the treatment or prevention of SIO. We investigated the efficacy of pamidronate on SIO in childhood nephropathy patients receiving long-term corticosteroid therapy. Methods: Forty-four children receiving high doses of steroids were enrolled in the study. There was no history of bone, liver, or endocrine disease. Patients were randomly classified into two groups, the control group and the study group. All patients received corticosteroids for 3 months. Control group took oral calcium supplements (500 mg/day) only, and the study group oral calcium and pamidronate (125 mg) for 3 months. Biochemical tests, long bone radiography, and bone mineral density (BMD) were performed in the first month and 3 months later in all patients. Results: The differences in the results of biochemical tests such as serum calcium, BUN, and cre atinine level obtained in the first month and three months later were not of statistical significance in both the control and the study groups. However, the mean BMD of the lumbar spine decreased from 0.654 ± 0.069 (g/cm2) to 0.631 ± 0.070 (g/cm2) in the control group (p = 0.0017), while it did not in the study group from 0.644 ± 0.189 (g/cm2) to 0.647 ± 0.214 (g/cm2). Conclusions: Pamidronate appears to be effective in preventing SIO in children with nephropathy requiring long-term steroid therapy. Further long-term follow-up studies regarding the efficacy and side effects appear to be necessary to set a more solid basis for such pediatric uses of bisphosphonates such as pamidronate.
Erythropoietin-Alpha Dosage Requirements in a Provincial Hemodialysis Population: Effect of Switching from Subcutaneous to Intravenous Administration
Authors: Raymond Colette B. , Collins David M. , Bernstein Keevin N. , Skwarchuk Dan E. , Vercaigne Lavern M.
Published: November 2005

Background: The purpose of this initiative was to compare erythropoietin-α doses in hemodialysis patients who changed from subcutaneous to intravenous administration. The Manitoba Renal Program switched routes due to concern about erythropoietin-associated pure red cell aplasia. Methods: We compared the erythropoie tin-α dosage requirements during subcutaneous administration (3 months pre-switch) and intravenous administration (months 4–6 post-switch). We also compared: hemoglobin, transferrin saturation (Tsat%), ferritin, and percent of patients receiving intravenous iron. The same erythropoietin-α regimen was initially used when patients were switched. Results: Of the 628 patients receiving erythropoietin-α, the data were complete for 400. The dose increased 26% (mean ± SD, 10,425 ± 7,330 vs. 13,125 ± 8,638 IU/week; p < 0.0001), despite similar hemoglobin, (mean ± SD, 11.5 ± 1.1g/dl (114.9 ± 11.2 g/l) vs. 11.3 ± 1.0 g/dl (113.5 ± 10.4 g/l); p = 0.0450) and iron parameters (Tsat 30.9%, ferritin 464 ng/ml (µg/l) vs. Tsat 28.7%, ferritin 538 ng/ml (µg/l)). For the subgroup of 84 patients who maintained target hemoglobin (10–11 g/dl or 110–120 g/l) for both periods, the dose increased 26% (mean ± SD, 8,393 ± 6,242 vs. 10,589 ± 7,049 IU/week; p < 0.0001) without a change in hemoglobin, (mean ± SD, 11.5 ± 0.3 g/dl (115.2 ± 3.0 g/l) vs. 11.5 ± 0.3 g/dl (114.9 ± 3.3 g/l); p = 0.5789). When stratified by subcutaneous dose, patients with the lowest dose (<5,000 IU/week) demonstrated the greatest increase (89%), and those with the highest dose (>20,000 IU/week) experienced no increase (–3%). Conclusion: Overall, erythropoietin-α doses increased by 26% when patients were converted from subcutaneous to intravenous administration.
High Serum C3 Predicts Poor Outcome in IgM Nephropathy
Authors: Myllymäki Juhani , Saha Heikki , Pasternack Amos , Helin Heikki , Mustonen Jukka
Published: November 2005

Background: IgM nephropathy (IgMN) is an idiopathic glomerulonephritis with mesangial IgM deposition. The etiology of the depositions and possible association of serum and mesangial immunoglobulins and complement findings with renal outcome in IgMN remain unknown. Here we brought out data supplementary to our previous findings by reporting associations of immunological parameters with the outcome of IgMN. Methods: Serum IgA, IgG, IgM, C3 and C4 were measured in 110 IgMN patients by single radial immunodiffusion or nephelometry. Mesangial IgA, IgG, IgM, C1q and C3 assessed in immunofluorescent study were graded as +/–. Seven histopathological parameters were semiquantitatively graded into three classes. The relationship of serum and mesangial immunoglobulin and complement findings with the clinical outcome and prognosis of IgMN was examined. Results: We found significantly lower serum IgG and higher serum C3 levels in patients with nephrotic syndrome. Serum C3 correlated with the severity of glomerular histopathological changes. Of immu nological parameters evaluated a low serum IgG/C3 ratio correlated best with the progression of renal disease. However, serum C3 was associated indepen dently with progression in the case of patients without nephrotic syndrome. Conclusions: In addition to previously reported factors, immunological parameters may also be helpful in determining the prognosis in IgMN. High serum C3 predicts poor outcome in IgMN, being associated with high-grade proteinuria, severe histopathological changes and progression.
Upregulation of Thymidine Phosphorylase in Chronic Glomerulonephritis and Its Role in Tubulointerstitial Injury
Authors: Wang Eun-Hui , Goh Yong Bok , Moon In Sung , Park Cho Hyun , Lee Kweon-Heang , Kang Sung Hak , Kang Chang Suk , Choi Yeong-Jin
Published: November 2005

Chronic tubulointerstitial injury (CTI), commonly a sequel to chronic glomerulonephritis (CGN), is associated with the proliferation of new blood vessels. Angiogenesis is an essential process in chronic inflammation, and is controlled by a number of angiogenic factors including thymidine phosphorylase (TP). Knowledge of TP in renal disease is still rudimentary, and its role in CGN has not been explored. We analyzed the expression of TP by RTPCR, immunohistology and in situ hybridization in 20 human kidneys with CGN. To evaluate the degree of angiogenesis, we counted the microvessel density (MVD). MVD was significantly higher in all categories of CGN, between 19.7 ± 7.7 and 58.9 ± 7.5, compared to control value, 12.7 ± 5.0 (p< 0.05). MVD was increased in areas of abundant mononuclear cell infiltration with minimal interstitial fibrosis, and decreased or absent in areas of marked fibrosis. There was a significant correlation between MVD and interstitial fibrosis (p < 0.0001). TP mRNA was upregulated for all categories of CGN. TP was strongly expressed by mononuclear inflammatory cells and in most atrophic tubules. Each MVD and interstitial volume was significantly correlated with both the number of TP+ mononuclear cells and TP+ tubular cells, respectively (p < 0.0001). We have demonstrated an upregulation of TP and increase in MVD in areas of CTI in a variety of CGN. The up-regulation of TP may contribute to angiogenesis, which may play a critical role in the progression of interstitial fibrosis in CGN.
Does Body Mass Index Predict Overweight in Native Asian Indians? A Study from a North Indian Population
Authors: Bhansali A. , Nagaprasad G. , Agarwal A. , Dutta P. , Bhadada S.
Published: November 2005

Aims: Body mass index (BMI) has been considered as a gold standard for defining overweight and obesity, and in western populations it has correlated with percentage body fat (%BF). However, data in native Asian Indians regarding BMI and %BF is conflicting and questions have been raised to redefine the BMI cut-off values in these subjects. Subjects and Methods: 150 healthy volunteers (79 men and 71 women aged 18–78 and 23–75 years respectively) were recruited for the study. Clinical examination was performed to exclude any systemic disease. Anthropometric measurements were done and %BF was calculated from skinfold thickness. Results: The BMI for men was 24.96 kg/m2 (±3.85) and for women was 25.75 kg/m2 (±4.39).%BF calculated by skinfold thickness was 21.94% (±5.92) in men and 35.15% (±5.77) in women. Receiver operating characteristic curve analysis showed a higher sensitivity (92%) and higher negative predictive value (95%) for the conventional cut-off value of the BMI (25 kg/m2) in identifying subjects with overweight with %BF of more than 25% in men. However, in females a BMI of 23.9 kg/m2 had a sensitivity of 84% and negative predictive value of 62% thereby decreasing the misclassification by 13% with %BF of more than 30% as compared to conventional BMI cut-off of >25 kg/m2. A comparison of BF data amongst Caucasians, Blacks and migrant ethnic Asians revealed inconspicuous differences in men. Conclusion: Native North Indian men had comparative BMI and %BF as that of their western counterparts.
Genetic Studies of IgA Nephropathy
Authors: Maxwell Patrick H. , Wang Yiming
Published: November 2005

IgA nephropathy is the commonest form of glomerulonephritis worldwide, but we still know relatively little about its pathogenesis. Potentially, genetic studies might provide new insights and suggest novel therapeutic approaches to this important cause of chronic kidney disease. Two approaches that are likely to yield new information are analysis of multiply affected pedigrees and large-scale, well-controlled association studies.
Expression of B7-H1 in Inflammatory Renal Tubular Epithelial Cells
Authors: Chen Yongwen , Zhang Jingbo , Li Jingyi , Zou Liyun , Zhao Tingting , Tang Yan , Wu Yuzhang
Published: November 2005

Background: Renal tubular epithelial cells (TECs) function as antigen-presenting cells (APCs) as they constitutively express MHC-II molecules and have the capacity to present peptide antigen to T cells. Nevertheless, co-stimulatory signals provided by TECs for regulating T cell activation have not been fully characterized. We therefore investigated the expression of B7-H1, a member of the B7 superfamily, on TECs under normal or pathologic conditions in vivo and analyzed the regulation and functional role of it after proinflammatory factors treatment in vitro. Methods: Immunohistological staining for B7-H1 on cryostat sections of core needle biopsies from patients with different renal diseases was examined. Furthermore, we also detected B7-H1 protein expression on cultured human TECs stimulated by various inflammatory factors and performed TEC/T-cell co-cultured experiment to determine TEC-associated B7-H1 in regulating CD4+ T cell activation as well as antigen presentation. Results: Significant B7-H1 protein was detected in TECs of diseased renal samples. Although the presence of B7-H1 does not have any correlation with clinicopathological variables, marked B7-H1 expression on sections without interstitial inflammation revealed that B7-H1 has some protective function. In vitro, the expression of B7-H1 on TECs was increased after TECs were stimulated with IL-1α, LPS, TNF-α, IFN-γ or anti-CD40. Co-cultured experiments revealed that TEC-related B7-H1 was identified as a strong inhibitor of CD4+ T-cell activation as assessed by increased cytokine production (interleukin-2 and interferon-γ) and expression levels of the T cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (clone MIH1). Interestingly, IL-2 production by C10 T cells after antigen presentation by murine TECs was also enhanced when the B7-H1/PD-1 pathway was interrupted. Conclusion: This study clearly shows that B7-H1 is an inducible renal tubular epithelial antigen that inhibits T cell activation. It is speculated that B7-H1/PD-1 pathway might play a role in protecting tubular epithelium from immune-mediated damage and active delivery of the B7-H1 inhibitory signal represents a novel therapeutic strategy in autoimmune renal diseases.
Murine Metanephric Mesenchyme Possesses Characteristics of Vascular Endothelial Cells in vitro
Authors: Usui Joichi , Yamada Risa , Kanemoto Katsuyoshi , Koyama Akio , Nagata Michio
Published: November 2005

Background/Aims: Although the renal microvasculature, including the glomerular capillaries, is generally considered to develop from the metanephric mesenchyme, this has not been unequivocally demonstrated. Using a murine metanephric mesenchymal cell line (MS7), we tested whether the metanephric mesenchyme expresses phenotypic characteristics of endothelial cells and differentiates into vascular endothelial cells in vitro. Methods: MS7 cells were examined for the mRNA expression of endothelial markers by reverse transcription (RT)-PCR. Moreover, we attempted to induce the appearance of new endothelial markers by stimulation with growth factors and exposure to hypoxia. Results: Before induction, MS7 cells expressed mRNA of fetal liver kinase 1 (Flk1), fms-like tyrosine kinase (Flt1), tyrosine kinase with Ig and EGF homology domains 2 (Tie2), CD31, and podocalyxin. However, they did not express mRNA for vascular endothelial-cadherin (VE-cadherin) or von Willebrand factor (vWF), which are markers specific for endothelial cells and mature endothelial cells. In the immunocytochemical analysis, MS7 absorbed DiI-acetylated LDL virtually, but the results of staining with anti-VE-cadherin, vWF, or CD31 antibodies were negative. MS7 cells that were cultured for 14 days after reaching confluence began to express VE-cadherin and vWF mRNA. In addition, immunofluorescence showed abundant granules stained with anti-vWF antibody in the cytoplasm. Stimulation with vascular endothelial growth factor (VEGF), or basic fibroblast growth factor (bFGF), or exposure to a hypoxic condition did not influence their characteristic changes. Conclusion: Our results suggest that metanephric mesenchymal (MS7) cells possess some characteristics of endothelial cells, and they are potent to differentiate into mature vascular endothelium in vitro.
Inhibition of Parathyroid Hormone: A Dose Equivalency Study of Paricalcitol and Doxercalciferol
Authors: Zisman Anna L. , Ghantous Walid , Schinleber Pamela , Roberts Laurie , Sprague Stuart M.
Published: November 2005

Introduction: Paricalcitol and doxercalciferol are effective in reducing parathyroid hormone PTH concentrations in patients with secondary hyperparathyroidism. The purpose of this study was to determine the relative dose of doxercalciferol (compared to paricalcitol) required to maintain equivalent PTH concentrations in dialysis patients. Methods: Chronic hemodialysis patients treated with a stable dose of paricalcitol for at least 3 months were randomized to receive doxercalciferol at either 35, 50, or 65% of the paricalcitol dose for 6 weeks. Serum iPTH, calcium, phosphorus, and albumin were determined at baseline and monitored every 2 weeks. A linear regression analysis of percent change in iPTH values by dose group was performed to determine the conversion factor. Results: 27 patients were enrolled. Initial iPTH, adjusted serum calcium, serum phosphorus, and Ca×P were similar among the treatment groups. Linear regression analysis demonstrated a conversion factor of 0.57 for the dose of doxercalciferol relative to paricalcitol resulting in equivalent suppression of iPTH. Corrected serum calcium, phosphorus, Ca×P product, as well as incidence of hypercalcemia, hyperphosphatemia and Ca×P >50 were similar for all groups. Conclusion: In patients on a maintenance dose of paricalcitol, dosing doxercalciferol at 55–60% of the paricalcitol dose results in comparable inhibition of PTH.
Activity of Systemic Lupus Erythematosus in End-Stage Renal Disease Patients: Study in a Brazilian Cohort
Authors: Ribeiro Francinne M. , Leite Marco Antonio P. , Velarde Guillermo Coca , Fabris Cristianne L. , Santos Renata C. , Lugon Jocemir R.
Published: November 2005

Background: Dialysis has been associated with lupus remission. We studied the prevalence of systemic lupus erythematosus (SLE) as a cause of end-stage renal disease (ESRD) in the metropolitan area of Rio de Janeiro and assessed disease activity in SLE patients on dialysis. Methods: Of 3,535 ESRD patients, 63 had SLE (1.8%). Fifty-seven entered the study (54 females, 3 males, 38 ± 10 years). Hemodialysis consisted of 3 sessions per week of about 4 h duration, blood flow of about 400 ml/min, bicarbonate dialysate ([Ca2+] = 2.5–3.5 mEq/l) at 500 ml/min and cellulose acetate or polysulfone dialyzers. Activity was initially defined as: non-renal (nr) SLE disease activity index (SLEDAI) of >0; use of at least 20 mg/day of prednisone; and/or any dose of another activity-controlling drug. Fifty-seven ESRD patients without SLE were used as controls. Results:Eighteen SLE patients were under drug treatment; of the remaining, 30 had an nrSLEDAI of >0 totaling 48 patients (84%) initially labeled as active. An apparent activity was also present in 21 controls (37%). Of those, 19 had an nrSLEDAI of <4. With a cutoff of ≧4, figures in each group would be 49 and 4%. Under this criterion, age was the only significant predictor of flare in our SLE ESRD population in a multivariate logistic regression model. Activity remained high in patients who were on dialysis for >5 years (7/18, 39%). Conclusion: SLE accounted for 1.8% of our ESRD patients. Application of SLEDAI to dialysis patients may require consideration of confounding factors related to the ESRD state. Even with a score of ≧4 as a cutoff, SLE activity in dialysis patients was high (49%) and long-lasting. Age was the major determinant of flare.
Glomerular and Tubular Epithelial Defects in kd/kd Mice Lead to Progressive Renal Failure
Authors: Madaio Michael P. , Ahima Rexford S. , Meade Ray , Rader Daniel J. , Mendoza Alberto , Peng Min , Tomaszewski John E. , Hancock Wayne W. , Gasser David L.
Published: November 2005

Background/Aim: The kd/kd mouse spontaneously develops severe and progressive nephritis leading to renal failure, characterized by cellular infiltration, tubular destruction and glomerular sclerosis. Recent identification of the mutant gene and the observation that podocytes are affected, led to the hypothesis that there are primary renal epithelial cell defects in this strain. Methods: Clinical and pathological signs of disease in a large cohort of kd/kd mice were studied by light microscopy, electron microscopy, and biochemical analyses of serum and urine at early stages of disease. Special attention was paid to mice under 140 days of age that had normal blood urea nitrogen (BUN) levels, but had developed albuminuria. Results: Although overt glomerular abnormalities are commonly observed either coincident with or after tubulointerstitial nephritis, we now report that albuminuria and visceral epithelial abnormalities, including hyperplasia and podocyte effacement may occur before the onset of either elevated BUN levels or severe interstitial nephritis, and this is accompanied by biochemical perturbations in serum typical of the nephrotic syndrome. Conclusions: The results suggest that the defect in kd/kd mice primarily affects both the tubular and glomerular visceral epithelium. The tubular epithelial defect triggers autoimmune interstitial nephritis, whereas a defect in podocytes leads to proteinuria and glomerulosclerosis. Thus, a single mitochondrial abnormality may result in differences in disease expression that vary with the type of epithelial cells. It is likely that the mitochrondrial perturbations in glomerular and tubular epithelia act in concert, through activation of different pathologic pathways, to accelerate disease progression leading to renal failure.
Effect of Thrombin on Permeability of Human Epithelial Cell Monolayers
Authors: Hayashi Shuichiro , Takeuchi Kazuhiko , Suzuki Shinya , Tsunoda Takatsugu , Tanaka Chikako , Majima Yuichi
Published: November 2005

Epithelial cells play an important role in maintaining the airway barrier, which is impaired in inflammatory conditions. Recently, thrombin was reported to be increased in the airway of patients with asthma, and thrombin has been shown to increase the permeability of endothelial cell monolayers. Therefore, we suspected that thrombin affects airway permeability. Calu-3 cell monolayers were established on microporous membranes of tissue culture cell inserts. We examined the effects of topically applied thrombin or thrombin receptor-activating peptide (TRAP) on: (1) transepithelial permeability (luminal to serosal transfer) of radiolabeled mannitol and albumin, (2) changes in electrical resistance, and (3) actin fiber content as assessed by fluorescence microscopy. Compared with untreated control cultures, treatment of the monolayers for 24 h with thrombin or TRAP significantly decreased the electrical resistance and increased the permeability to mannitol and albumin. In addition, these treatments enhanced the appearance of actin stress fibers, and small gaps became visible at areas of cell-cell contact. Thrombin appears to increase epithelial permeability by receptor-mediated reorganization of the actin network in airway epithelial cells. This is likely to contribute to the impairment of the airway barrier function.