bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulatory Effect of Ghrelin on Isolated Porcine Somatotropes
Authors: Glavaski-Joksimovic Aleksandra , Jeftinija Ksenija , Scanes Colin G. , Anderson Lloyd L. , Jeftinija Srdija
Published: July 2003

Research on the mechanism for growth hormone secretagogue (GHS) induction of growth hormone secretion led to the discovery of the GHS receptor (GHS-R) and later to ghrelin, an endogenous ligand for GHS-R. The ability of ghrelin to induce an increase in the intracellular Ca2+ concentration – [Ca2+]i – in somatotropes was examined in dispersed porcine pituitary cells using a calcium imaging system. Somatotropes were functionally identified by application of human growth hormone releasing hormone. Ghrelin increased the [Ca2+]i in a dose-dependent manner in 98% of the cells that responded to human growth hormone releasing hormone. In the presence of (D-Lys3)-GHRP-6, a specific receptor antagonist of GHS-R, the increase in [Ca2+]i evoked by ghrelin was decreased. Pretreatment of cultures with somatostatin or neuropeptide Y reduced the ghrelin-induced increase of [Ca2+]i. The stimulatory effect of ghrelin on somatotropes was greatly attentuated in low-calcium saline and blocked by nifedipine, an L-type calcium channel blocker, suggesting involvement of calcium channels. In a zero Na+ solution, the stimulatory effect of ghrelin on somatotropes was decreased, suggesting that besides calcium channels, sodium channels are also involved in ghrelin-induced calcium transients. Either SQ-22536, an adenylyl cyclase inhibitor, or U73122, a phospholipase C inhibitor, decreased the stimulatory effects of ghrelin on [Ca2+]i transiently, indicating the involvement of adenylyl cyclase-cyclic adenosine monophosphate and phospholipase C inositol 1,4,5-trisphosphate pathways. The nonpeptidyl GHS, L-692,585 (L-585), induced changes in [Ca2+]i similar to those observed with ghrelin. Application of L-585 after ghrelin did not have additive effects on [Ca2+]i. Preapplication of L-585 blocked the stimulatory effect of ghrelin on somatotropes. Simultaneous application of ghrelin and L-585 did not cause an additive increase in [Ca2+]i. Our results suggest that the actions of ghrelin and synthetic GHS closely parallel each other, in a manner that is consistent with an increase of hormone secretion.
Activation of the Somatotropic Axis by Testosterone in Adult Men: Evidence for a Role of Hypothalamic Growth Hormone-Releasing Hormone
Authors: Bondanelli Marta , Ambrosio Maria Rosaria , Margutti Angelo , Franceschetti Paola , Zatelli Maria Chiara , degli Uberti Ettore C.
Published: July 2003

Testosterone (T) is known to affect the growth hormone (GH) axis. However, the mechanisms underlying the activation of GH secretion by T still remain to be clarified. Available data in animals and humans have shown that withdrawal of somatostatin (SRIH) infusion induces a GH-releasing hormone (GHRH)-mediated rebound release of GH, and there is accumulating evidence that SRIH infusion withdrawal may be a useful test to probe the GHRH function in vivo. With the aim of investigating whether the stimulatory effect of androgens on GH release in man could be accounted for by activation of the hypothalamic GHRH tone, we evaluated the plasma GH response to SRIH withdrawal in 10 patients aged 29.6 ± 2.4 years (mean ± SEM), diagnosed with hypergonadotropic hypogonadism, before and after a 6-month replacement therapy with T enanthate (250 mg every 3 weeks, i.m.), and in 10 healthy men, aged 26.7 ± 2.8 years. To verify whether the modulation of GH secretion by T could also be mediated through changes in SRIH tone and/or pituitary releasable pool, we examined GH secretory responses to combined GHRH and L-arginine (ARG) in the same individuals. Basal plasma concentrations of GH (0.48 ± 0.11 µg/l) and IGF-I (23.79 ± 1.83 nmol/l) were significantly lower in untreated hypogonadal patients than in healthy men, and significantly increased after T replacement therapy (GH 1.13 ± 0.28 µg/l; IGF-I 28.71 ± 1.46 nmol/l). The mean ΔGH peak after SRIH withdrawal recorded in untreated hypogonadal men (2.65 ± 0.86 µg/l) was significantly (p < 0.05) lower than that observed in healthy men (6.53 ± 1.33 µg/l) and significantly increased after T replacement therapy (5.52 ± 1.25 µg/l). The GH responses to GHRH combined with ARG (a functional SRIH antagonist) were not significantly different between healthy men and untreated hypogonadal patients, and were not significantly affected by T treatment. Plasma T and estradiol (E2) levels significantly correlated with ΔGH peak after SRIH withdrawal in healthy men and in T-treated hypogonadal patients, whereas in untreated patients they did not. No significant correlation was found between GH areas under the curve after GHRH + ARG test and T and E2 plasma levels in either healthy men or in hypogonadal patients (both before and after T replacement). These findings are consistent with the view that in humans the stimulatory action of T on the GH axis appears to be mediated at the hypothalamic level primarily by promoting GHRH function.
Effects of Treadmill Running on Brain Activation and the Corticotropin-Releasing Hormone System
Authors: Timofeeva Elena , Huang Qingling , Richard Denis
Published: July 2003

The present study was conducted to investigate the effects of treadmill running on the corticotropin-releasing hormone (CRH), CRH receptor type 1 (CRH-R1) and CRH-binding protein (CRH-BP) in the brain of rats that were killed either at rest, immediately after 60 min of treadmill running, or 180 min following a 60-min session of intensive exercise. The expression of the neuronal activity marker c-fos was also determined in the three conditions of this study. The levels of c-fos mRNA immediately following running were high in the cortex, caudate-putamen, lateral septum, bed nucleus of the stria terminalis, dorsal and medial thalamus, hypothalamus, pontine nuclei, locus coeruleus and hypoglossal nucleus. In most brain regions investigated, excluding the locus coeruleus and the cingulate cortex, c-fos mRNA expression returned to control levels after 2 h of recovery. The highest concentration of cells co-expressing the protein Fos and CRH mRNA neurons was found in the parvocellular part of the paraventricular nucleus, which also expressed CRH heteronuclear RNA and CRH-R1 mRNA. The medial preoptic area (MPOA), the medial mammillary nucleus and the posterior hypothalamic as well as the somatosensory cortex, the medial geniculate nucleus, the reticulotegmental nucleus, and Barrington’s nucleus also co-expressed Fos and CRH mRNA. The expression of CRH-BP gene was induced in the MPOA following running. In summary, the present study demonstrates that treadmill running leads to a strong expression of c-fos mRNA that is widely distributed throughout the brain. c-fos mRNA was found in structures of the somatosensory and somatomotor systems, indicating that these regions were activated during exercise. The pattern of distribution of c-fos mRNA showed similarities with that triggered by neurogenic and systemic stresses. The present results also indicate that treadmill running can strongly activate the hypophysiotropic CRH system, which suggests, in agreement with the pattern of c-fos mRNA distribution, that treadmill running has a strong stress component.
Involvement of Mesolimbic Structures in Short-Term Sodium Depletion: In situ Hybridization and Ligand-Binding Analyses
Authors: Lucas Louis R. , Grillo Claudia A. , McEwen Bruce S.
Published: July 2003

Acute treatment with the diuretic furosemide (Lasix) produces a reduction in plasma Na+ and volume as well as increased thirst and salt appetite. The resulting hypovolemia stimulates the well-known counter-regulatory physiological response from the renin-angiotensin-aldosterone system. However, the neurochemical players underpinning the behavioral responses of thirst and salt appetite are less clear. Previously, we have reported that salt-replete deoxycorticosterone (DOCA) treatment activates mesolimbic structures associated with reward and goal-seeking behavior. The present study was designed to test whether the same brain regions are affected in a salt-depleted state. In experiment 1, two groups of adult male Sprague-Dawley (SD) rats were injected with Lasix (10 mg/rat, s.c.) and 18 h later were allowed access either to 2% NaCl solution (‘Lasix+salt’) or only to tap water (‘Lasixnosalt’) for 2 h. For comparison purposes, a third group received an isotonic saline injection instead of Lasix and was allowed access to the 2% salt solution (Vehicle). All groups were permitted 24 h access to tap water. We found no differences in dynorphin-mRNA levels in any striatal and accumbal regions among any of the treatment groups. However, as found previously in DOCA-treated rats, there were increased enkephalin (ENK)-mRNA and decreased dopamine transporter (DAT) binding levels throughout the striatum in Lasix+salt and decreased ENK-mRNA in Lasixnosalt rats versus Vehicle. In experiment 2, the involvement of the ENKergic and/or dopaminergic system was tested in rats divided into the same three groups described in experiment 1. However, before access to salt or water, the Lasix+salt and the vehicle groups were administered either a δ-opioid, naltrindole or a dopamine D2 antagonist, raclopride. Only the naltrindole-treated rats showed a blunted intake of salt solution. Thus, these findings along with our neurochemical results suggest that mesolimbic enkephalin might impact salt intake through dopaminergic systems.
Alteration in Sex-Specific Behaviors in Male Mice Lacking the Aromatase Gene
Authors: Matsumoto Takahiro , Honda Shin-ichiro , Harada Nobuhiro
Published: July 2003

Brain aromatase (P450arom) is a key enzyme in estrogen biosynthesis from testicular androgens. This local aromatization in neural tissues is thought to be an important process for sexual differentiation and activation of sexual behavior in male rodents. To determine the functional significance of the aromatase gene in development and activation of sex-specific behavior, we analyzed a series of behavioral profiles in gonadally intact male mice with targeted disruption of exons 1 and 2 of the aromatase gene (ArKO). In most cases, ArKO males were infertile and showed deficits in male sexual behavior including mount, intromission and ejaculation. Noncontact penile erection was not significantly affected by deletion of the aromatase gene. A great reduction of aggressive behavior against male intruders was also observed in ArKO males, while they tended to exhibit aggression toward estrous females during male copulatory tests. Furthermore, 73% of ArKO males showed infanticide toward pups, whereas characteristic parental behavior, but not infanticide, was observed in wild-type males. These results support the brain aromatization hypothesis and indicate that aromatase gene expression is a critical step not only for motivational and consummatory aspects of male sexual behavior, but also for aggressive and parental behaviors in male mice.
Tamoxifen Induces Gonadotropin-Releasing Hormone Self-Priming through an Estrogen-Dependent Progesterone Receptor Expression in the Gonadotrope of the Rat
Authors: Bellido Carmina , Martín de las Mulas Juana , Tena-Sempere Manuel , Aguilar Rafaela , Alonso Rafael , Sánchez-Criado José E.
Published: July 2003

Tamoxifen (TX) is an antiestrogen with varying levels of antagonist/agonist activity on the reproductive axis of the rat. It has been reported that TX, in contrast to other selective estrogen receptor modulators (SERMs), increases the content of cytosolic estrogen receptors (ER) in the gonadotrope and induces gonadotropin releasing hormone (GnRH) self-priming in the absence of E. GnRH priming is believed to be a consequence of E-dependent progesterone receptor (PR) activation. The purpose of this study was to determine whether TX induces PR expression in the gonadotrope in an E-dependent manner, and whether the blockade of PR activation affects TX-dependent GnRH self-priming in ovariectomized (OVX) rats. Chronic OVX rats were injected (sc) over 3 days with 25 µg estradiol benzoate (EB), 3 mg TX, 0.5 mg RU58668, a ‘pure’ anti-E (aE), 2 mg RU38486, an anti-P at the receptor (aP), TX+aE and TX+aP. Controls were given 0.2 ml oil. While EB and TX increased mRNA for both PR A+B and PR B expression and the number and intensity of nuclei immunoreactive (IR) for PR in the gonadotrope, the aE and aP given alone had no effect on either PR mRNA levels or nuclear PR-IR. The aE reduced the effect of TX on PR expression (mRNA and nuclear IR) while the aP slightly reduced nuclear PR-IR only. In addition, pituitaries from each of the seven groups were incubated with: 10–8M E2, 10–7M TX, 10–8M aE, 10–8M aP, TX+aE, TX+aP or medium alone, respectively. Pituitaries were tested for GnRH self-priming (two pulses of 15 min 1 h apart) and the secretion of LH and PRL determined by specific RIAs. Pituitaries from rats treated with EB and incubated with E2 had increased basal and GnRH-stimulated luteinizing hormone (LH) and prolactin (PRL) secretion and GnRH self-priming. TX reduced basal and stimulated LH secretion, increased PRL secretion and induced a robust GnRH self-priming. All these effects of TX were blocked by the aE, while the aP blocked GnRH self-priming only. In conclusion, tamoxifen induced PR expression (mRNA and nuclear IR) in the gonadotrope in an E-dependent manner, while activation of these PR through intracellular signaling of GnRH induced GnRH self-priming.
Medulloblastoma: Present Concepts of Stratification into Risk Groups
Authors: Packer Roger J. , Rood Brian R. , MacDonald Tobey J.
Published: July 2003

For the past two decades, staging studies have been used to stratify children with medulloblastoma into risk groups. Therapeutic approaches have been based on separation of patients into ‘average-risk’ and ‘poor-risk’ categories. The extent of disease at diagnosis has been most reproducibly shown to be of prognostic significance, but age at diagnosis and amount of residual disease after surgery or extent of resection have also been commonly incorporated into stratification schemata. Tumor histology has been variably related to outcome. Biologic markers, especially molecular genetic findings, have not yet been incorporated into risk classifications, but will likely add to the understanding of medulloblastoma and may significantly alter concepts of staging and treatment.
The Use of Gene Expression Analysis to Gain Insights into Signaling Mechanisms of Metastatic Medulloblastoma
Authors: Chopra Arun , Brown Kevin M. , Rood Brian R. , Packer Roger J. , MacDonald Tobey J.
Published: July 2003

Metastasis is the leading cause of treatment failure in medulloblastoma. Understanding the genetic regulation of metastasis may aid in the development of novel treatments. We therefore performed in silico analysis of the mRNA expression of 83 medulloblastomas compiled from two independent microarray studies by focusing on 135 genes most frequently linked to metastasis in other tumors. We then asked whether expression of these genes correlated with metastasis in the medulloblastoma array data sets. We found the platelet-derived growth factor receptor alpha, early growth response protein 1 and insulin-like growth factor 2 genes as well as several genes associated with MYCC and ERBB2 overexpressed by at least 2-fold in metastatic tumors in both array data sets. We conclude that these genes may interact to promote prometastatic signaling in medulloblastoma.
Sustained Raised Intracranial Pressure Implicated Only by Pattern Reversal Visual Evoked Potentials after Cranial Vault Expansion Surgery
Authors: Liasis Alki , Thompson Dorothy A. , Hayward Richard , Nischal Ken K.
Published: July 2003

Craniosynostosis, the premature fusion of cranial sutures, may be associated with raised intracranial pressure (ICP) with or without a reduced intracranial volume. Regardless of the aetiology, raised ICP may result in optic neuropathy, the timely detection of which can prevent further visual deterioration. Raised ICP is usually treated with craniofacial surgery such as cranial vault expansion. In this case study, we recorded serial pattern reversal visual evoked potentials (pVEPs) and obtained digital optic disc images before and after cranial vault expansion surgery. The amplitude of the pVEPs continued to decrease after cranial vault expansion surgery, prompting further neuroimaging that implicated a blocked ventriculo-peritoneal shunt. Only after shunt revision did the pVEP amplitude increase. Throughout the monitoring period, there was no change in the appearance of either the right or left optic disk, nor a consistent change in visual acuity.
Villous Hypertrophy versus Choroid Plexus Papilloma: A Case Report Demonstrating a Diagnostic Role for the Proliferation Index
Authors: D’Ambrosio Anthony L. , O’Toole John E. , Connolly Jr. E. Sander , Feldstein Neil A.
Published: July 2003

Diffuse bilateral enlargement of the choroid plexus has long been appreciated as a cause of shunt-resistant hydrocephalus in infants, most often secondary to cerebrospinal fluid overproduction. Despite the fact that such lesions have interchangeably been termed ‘villous hypertrophy’ (VH) or ‘bilateral choroid plexus papilloma’ (CPP), little attention has been paid to the pathological distinctions that characterize these two entities. We present a case of presumed VH in a 2-week-old female presenting with cerebrospinal fluid production-dependent hydrocephalus that ultimately required bilateral surgical ablation of the choroid plexus. Although the preoperative radiological diagnosis was consistent with VH, postoperative histological analysis suggested bilateral CPP. The neoplastic nature of the lesion was confirmed by specific staining for the proliferation index, showing an MIB-1 labeling index of 4%, characteristic of papilloma. Routine imaging and histological grading of choroid plexus hypertrophy and papilloma have not provided a reliable means of predicting malignant behavior or recurrence after surgical resection. Moreover, none of the previously reported cases of VH in the literature have analyzed pathological specimens for cellular proliferative potential. Therefore, we review the literature on VH and bilateral CPP and discuss the diagnostic and possible prognostic implications of distinguishing these variants by utilizing the MIB-1 marker for the proliferation index.
Chiari II Malformation and Occult Spinal Dysraphism
Authors: Tubbs R. Shane , Wellons III John C. , Grabb Paul A. , Oakes W. Jerry
Published: July 2003

We report two cases of children with occult spinal dysraphism who were also found to have many associated brain anomalies seen in the Chiari II malformation. No previous report has commented on the possible association between the Chiari II malformation and the ‘closed’ form of neural tube defect. One child had symptoms referable to pathology at the craniocervical junction. Neither child had cutaneous stigmata associated with occult spinal dysraphism over the caudal midline spine. These cases, although seemingly rare, lend support to the theories that the association between the Chiari II malformation and patients with myelomeningoceles is due to dysgenesis of the rostral and caudal neural tube. These cases are also important as refutation of earlier theories that link these two entities by proposing that the Chiari II malformation is due to overdrainage of cerebrospinal fluid at the site of myelomeningocele.
Management of Acute Cholangitis
Authors: Gouma Dirk J.
Published: July 2003

Endoscopic sphincterotomy (ES) is the treatment of choice for patients with (severe) acute cholangitis. For fit patients without co-morbidity with mild cholangitis and CBD stones with a gallbladder in situ, the one-stage laparoscopic approach could be considered as an alternative in centers with sufficient experience. The results of both procedures are comparable. Open surgery is relatively safe. It has a high success rate, good/excellent long-term results, but is not very attractive for the patient and should not be used routinely nowadays. Therefore, the indication should be limited for management of severe complications after ES as perforations of the duodenum, large CBD stones and patients with Mirizzi’s syndrome or intrahepatic stones with stenosis of the bile duct. ES as primary treatment for CBD stones should be followed by laparoscopic cholecystectomy in ‘fit’ patients. In patients with malignant disease, particularly after repeated stent failure and subsequent cholangitis, bypass surgery should be considered in patients with a life expectancy of >3 months.
Modern Phase-Specific Management of Acute Pancreatitis
Authors: Werner Jens , Uhl Waldemar , Hartwig Werner , Hackert Thilo , Müller Christophe , Strobel Oliver , Büchler Markus W.
Published: July 2003

The management of acute necrotizing pancreatitis has changed significantly over the past years. In contrast to the early surgical intervention of the past, there is now a strong tendency towards a more conservative approach. Initially, severe acute pancreatitis is characterized by the systemic inflammatory response syndrome. Early management is non-surgically and solely supportive. A specific treatment still does not exist. In cases of necrotizing disease, prophylactic antibiotics should be applied to reduce late septic complications. Today, more patients survive the first phase of severe pancreatitis due to improvements of intensive care medicine, thus increasing the risk of later sepsis. Pancreatic infection is the major risk factor with regard to morbidity and mortality in the second phase of severe acute pancreatitis. Whereas early surgery and surgery for sterile necrosis can only be recommended in selected cases, pancreatic infection is a well-accepted indication for surgical treatment in the second phase of the disease. Surgery should ideally be postponed until 4 weeks after the onset of symptoms, as necrosis is well demarcated at that time. Three surgical techniques can be performed with comparable results regarding mortality: necrosectomy combined with the (1) open packing technique, (2) planned staged relaparotomies with repeated lavage, or (3) closed continuous lavage of the retroperitoneum. However, the latter method seems to be associated with the lowest morbidity compared to the other approaches.
Surgical Treatment of Severe Inflammatory Bowel Diseases
Authors: Leowardi Christine , Heuschen Gundi , Kienle Peter , Heuschen Udo , Schmidt Jan
Published: July 2003

Surgical treatment of severe inflammatory bowel diseases is required in failed medical treatment, in emergencies and for complications. Indications for surgery and operative techniques have changed significantly over the last few years. There is a clear tendency towards earlier and less invasive surgical interventions performed in specialized and experienced centers. Improved quality of life of patients with Crohn’s disease or ulcerative colitis after surgical therapy supports an earlier consideration of the surgical treatment option. A close cooperation with the involved gastroenterologist is mandatory in this context.
Intestinal Obstruction and Perforation – The Role of the Surgeon
Authors: Dervenis Christos , Delis Spiros , Filippou Dimitrios , Avgerinos Costas
Published: July 2003

Intestinal obstruction and perforation are always a challenge for the surgeon, not only in respect to the surgical option offered to the patient, but also to the ability to accurately diagnose and stage the disease. The understanding of the underlying pathophysiological mechanism is also very important in order to classify each patient in order to receive the more appropriate treatment. Mechanisms of obstruction and perforation, methods of diagnosis as well as prevention and treatment of the disease were reviewed.
F₀ Timing in Kinyarwanda
Authors: Myers Scott
Published: July 2003

In Kinyarwanda (Bantu, Rwanda), a high tone can occur on either the first or the second mora of a syllable. A study of f₀ timing in the language was undertaken to determine how such a contrast is realized phonetically, and how this realization is affected by phrase position, word position, and distance from a following high tone. The study also aimed to explore a reported effect of ‘tone anticipation’ (raising of pitch in a syllable before a high tone) in the language. The study found significant effects of the position of a tone within the syllable, its position within the phrase, and its position with respect to following high tones. Models of f₀ timing in Kinyarwanda are proposed, demonstrating the role of moras in phonetic implementation of tone. These models clarify issues regarding the phonological representation of tones in Kinyarwanda, and the division between phonetic patterns and phonological ones.
Calibrated Automated Thrombin Generation Measurement in Clotting Plasma
Authors: Hemker H. Coenraad , Giesen Peter , Al Dieri Raed , Regnault Véronique , de Smedt Eric , Wagenvoord Rob , Lecompte Thomas , Béguin Suzette
Published: July 2003

Calibrated automated thrombography displays the concentration of thrombin in clotting plasma with or without platelets (platelet-rich plasma/platelet-poor plasma, PRP/PPP) in up to 48 samples by monitoring the splitting of a fluorogenic substrate and comparing it to a constant known thrombin activity in a parallel, non-clotting sample. Thus, the non-linearity of the reaction rate with thrombin concentration is compensated for, and adding an excess of substrate can be avoided. Standard conditions were established at which acceptable experimental variation accompanies sensitivity to pathological changes. The coefficients of variation of the surface under the curve (endogenous thrombin potential) are: within experiment ∼3%; intra-individual: <5% in PPP, <8% in PRP; interindividual 15% in PPP and 19% in PRP. In PPP, calibrated automated thrombography shows all clotting factor deficiencies (except factor XIII) and the effect of all anticoagulants [AVK, heparin(-likes), direct inhibitors]. In PRP, it is diminished in von Willebrand’s disease, but it also shows the effect of platelet inhibitors (e.g. aspirin and abciximab). Addition of activated protein C (APC) or thrombomodulin inhibits thrombin generation and reflects disorders of the APC system (congenital and acquired resistance, deficiencies and lupus antibodies) independent of concomitant inhibition of the procoagulant pathway as for example by anticoagulants.
Factor VIII Inhibitor-Bypassing Agents Act by Inducing Thrombin Generation and Can Be Monitored by a Thrombin Generation Assay
Authors: Turecek P.L. , Váradi K. , Keil B. , Negrier C. , Berntorp E. , Astermark J. , Bordet J.-C. , Morfini M. , Linari S. , Schwarz H.P.
Published: July 2003

Factor VIII (FVIII)-bypassing agents have complex modes of action but all control bleeding in inhibitor patients by triggering the generation of thrombin. No routine test is available for monitoring this therapy in patients with inhibitors against FVIII. We present an assay that records FEIBA- or FVIIa-mediated changes in thrombin generation (TG) in FVIII inhibitor plasma samples. In plasma samples spiked with FEIBA TG was normalized above 0.4 U/ml, while for recombinant FVIIa (rFVIIa) more than 12.5 µg/ml were required to induce TG in the absence of tissue factor (TF). Addition of TF increased the TG potential of rFVIIa in vitro. This assay seems suitable for monitoring the pharmacokinetics of inhibitor bypassing agents during treatment and possibly for predicting responses to treatment.
Calibrated Automated Thrombin Generation in Frozen-Thawed Platelet-Rich Plasma to Detect Hypercoagulability
Authors: Regnault Véronique , Béguin Suzette , Lecompte Thomas
Published: July 2003

To enhance the practical applicability of the calibrated automated thrombogram (CAT) we investigated whether frozen-thawed platelet-rich plasma (ft-PRP) can be used to assess the function of the protein C inhibitory pathway, while preserving the natural phospholipid composition. Recalcified ft-PRP triggered with 0.5 pM recombinant human tissue factor shows a median thrombin potential of 1,779 nM·min, against 1,576 nM·min for fresh PRP. To obtain ∼70% inhibition, 6.7 nM activated protein C (APC) has to be added, instead of 25 nM in fresh PRP; so the relative APC resistance of PRP appears to depend upon the presence of intact platelets. Factor VIII, added to normal ft-PRP to obtain a concentration of 3.3 U/ml, increases the thrombin potential in the presence of APC 1.5-fold, from 524 to 808 nM·min, in keeping with previously published increases in thrombotic risk in patients with high factor VIII levels. We conclude that thrombography in ft-PRP, with and without added APC, can be used to assess known risk factors for thrombosis, which allows the design of large clinical studies aimed at proving the relationship between thrombin potential and clinical outcome.
Thrombin Generation Measurement in Factor VII-Depleted Plasmas Compared to Inherited Factor VII-Deficient Plasmas
Authors: Giansily-Blaizot Muriel , Al Dieri Raed , Schved Jean-François
Published: July 2003

Activated factor VII (FVIIa)/tissue factor enzyme complex is the initiator of the coagulation cascade in vivo. FVIIa is of particular interest because it has been found to induce haemostasis in various bleeding disorders. In order to evaluate the FVII threshold that is required to initiate the clotting cascade, we measured thrombin generation in FVII-depleted plasmas spiked with increasing amounts of normal pooled plasma and in inherited FVII-deficient plasmas. According to the literature, only trace amounts of FVII are sufficient to initiate blood coagulation in vitro. By contrast, results on inherited FVII-deficient plasmas showed a wide variety of the amounts of thrombin generated in plasmas with the same FVII coagulant activity levels. This suggests that the threshold of FVII required to initiate haemostasis in vivo depends on one or more, hitherto unknown, plasmatic or cellular factors.
A Critical Evaluation of the Prothrombin Time for Monitoring Oral Anticoagulant Therapy
Authors: Jackson Craig M. , Esnouf M. Peter , Lindahl Tomas L.
Published: July 2003

The Quick prothrombin time is the most common clotting test performed, principally for monitoring oral anticoagulant therapy. The International Normalized Ratio (INR) for comparing patient results from prothrombin time measurements and the International Standardized Index (ISI) for achieving greater consistency of results using different thromboplastins have made it possible to compare the results of vitamin K antagonist drug therapy that was impossible before the introduction of the INR and ISI. However, INR values obtained from the same patient plasma sample using different thromboplastins are significantly different. This is so even when the thromboplastins have nearly the same ISI values. We suggest that investigation of patient-specific differences can provide a means by which the INR discrepancies can be identified and understood and thus lead to better methods for monitoring oral anticoagulant therapy.
Thrombin Generation in Platelet-Rich Plasma as a Tool for the Detection of Hypercoagulability in Young Stroke Patients
Authors: Faber C.G. , Lodder J. , Kessels F. , Troost J.
Published: July 2003

The time course of the concentration of active thrombin in clotting plasma (the thrombogram) was measured by subsampling from platelet-rich plasma (PRP) and continuous chromogenic measurement of platelet-poor plasma (PPP) in 41 stroke patients under the age of 50, in whom stroke could not be attributed to cardioembolic disease, arterial dissection or vasculitis. A significant increase in the area under the thrombogram (endogenous thrombin potential, ETP) was seen in 23 patients. In 9 of them, ETP was increased in PRP but normal in PPP. High ETP in PRP was significantly associated with stroke, both in the middle and in the highest tercile of the ETP (odds ratio 5.1, range 1.8–15.1, and 3.7, range 1.3–10.3, respectively). A decreased sensitivity to the inhibitory action of thrombomodulin (TM) on thrombin generation was observed in 5 of 37 cases. No further definition of the cause of increased thrombin generation or TM resistance was attempted, except for the role of von Willebrand factor (vWF). ETP in PRP, platelet-derived procoagulant activity and vWF were correlated and higher in patients than in controls (p = 0.002, p = 0.045 and p = 0.0006, respectively). This confirms the correlation between vWF level and stroke at young age found in epidemiological studies. It suggests that the role of vWF in thrombin generation, which has been demonstrated in vitro, may be the underlying mechanism of this correlation. In summary, hypercoagulability, defined as an increased capacity of the platelet plasma system to form thrombin, is found in over half of the patients under 50 years with an otherwise unexplained stroke. Sometimes it is due to increased plasma factor activity, sometimes to an increased procoagulant activity of the platelets.
Striking and Rapid Improvement of Plaque Psoriasis with Infliximab
Authors: Al-Salem Iqbal Hamad
Published: July 2003

Infliximab, an anti-tumor-necrosis-factor-α antibody, is a new line of therapy for psoriasis on the basis that tumor necrosis factor α antibody plays an important role in the pathogenesis of this disease. We report 2 patients with severe active psoriatic arthritis despite treatment with methotrexate. Both patients were started on infliximab infusion at a dose of 5 mg/kg body weight for their active psoriatic arthritis to be given according to a specific treatment protocol. Dramatic improvement of their psoriatic skin lesions was noted concomitantly with improvement in their arthritis symptoms shortly after starting the treatment program. No side effects were noted by the patients during their treatment course.
Troglitazone Inhibits Isolated Cell Proliferation, and Induces Apoptosis in Isolated Rat Mesangial Cells
Authors: Tsuchiya Takahumi , Shimizu Hiroyuki , Shimomura Kenju , Mori Masatomo
Published: July 2003

Background/Aims: Troglitazone is one of thiazolidinedione derivatives as a high affinity ligand for peroxisome proliferator-activated receptor-gamma (PPAR-γ). The in vivo studies demonstrated that troglitazone ameliorated microalbuminuria. There have been few reports about direct effect of thiazolidinedione derivatives on mesangial cell function. We determined the effect of troglitazone on isolated rat mesangial cell proliferation. Methods: We determined PPAR-γ mRNA expression in isolated rat mesangial cells. Chronic effects of 10–6 to 10–4 mol/l troglitazone on mesangial cell proliferation and mitogen-activated protein (MAP) kinase activity were also determined. The effects of troglitazone on apoptosis were investigated in rat mesangial cells. Results: Rat PPAR-γ mRNA was detected in isolated rat mesangial cells. Living cell number, assessed by colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay, was significantly decreased with 10–4 mol/l troglitazone. The addition of 10–6 to 10–4 mol/l troglitazone dose-dependently inhibited 5-bromo-2′-deoxyuridine (BrdU) uptake into isolated rat mesangial cells. The addition of 10–4 and 10–5 mol/l troglitazone significantly reduced MAP kinase activity. Troglitazone at the concentrations of 10–6 to 10–4 mol/l dose-dependently increased DNA fragmentation rates, indicating that troglitazone may cause apoptosis in rat mesangial cells. Bax and Bcl-xL proteins were not changed, although Bcl-2 proteins increased with troglitazone. Conclusions: The present data demonstrated that troglitazone inhibits cell proliferation, and induces apoptosis in rat mesangial cells, raising a possibility that it directly affects renal function.
Tackling the Shortage of Donor Kidneys: How to Use the Best that We Have
Authors: Perico Norberto , Ruggenenti Piero , Scalamogna Mario , Remuzzi Giuseppe
Published: July 2003

Shortage of kidney donor is still a major limitation for renal transplantation programs. This review focuses on the emerging practices, adopted to increase transplant activities, of expanding the criteria for donor and recipient selection without exposing the recipient to the drawbacks of a graft with inadequate nephron mass. Expanding the donor pool inevitably led to consideration for kidney transplantation of organs from older donors or from donors with hypertension, diabetes or other renal diseases. To fit the reduced performance of these suboptimal organs with the renal requirement of the recipient, selection of recipients with reduced metabolic requirements or increase of nephron mass by simultaneous transplantation of two suboptimal kidneys in the same recipient have been pursued. However, a critical aspect of both approaches is to quantify functioning nephron mass provided to the recipient by pre-transplant kidney biopsies. Morphological parameters assessed on kidney biopsies at the time of donor evaluation may serve to quantify the preserved tissue and to discriminate chronic irreversible lesions from acute changes that may account for a transiently impaired renal function in the donor, but that may recover after transplant.
Interleukin-8 and Tumor Necrosis Factor-Alpha Are Increased in Minimal Change Disease but Do Not Alter Albumin Permeability
Authors: Cho Min Hyun , Lee Hwan Seok , Choe Byung Ho , Kwon Soon Hak , Chung Ki Young , Koo Ja Hoon , Ko Cheol Woo
Published: July 2003

Aims: Minimal change disease (MCD) is the most common primary nephrotic syndrome in children. Some suggested that interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) are involved in the pathogenesis of MCD. This study was done to see changes of plasma and urinary IL-8, TNF-α, and their effects on determination of permeability of glomerular basement membrane (BM) contributed by heparan sulfate proteoglycan (HSPG). Methods: Study patients consisted of 19 biopsy-proven MCD children aged 2–15 years old. Both plasma, urinary IL-8 and TNF-α were measured. Employing the Millicell system, IL-8 and TNF-α were screened for the permeability factors. We examined whether IL-8 and TNF-α regulated BM HSPG gene expression and HS synthesis in the glomerular epithelial cells (GECs). Results: Urinary IL-8 during relapse was significantly increased when compared with that of during remission or controls (13,996 ± 2,811 vs. 2,941 ± 373, 5,331 ± 640 ng/mg·cr) (p < 0.05). Urinary TNF-α during relapse was also significantly increased (364.4 ± 51.2 vs. 155.3 ± 20.8, 36.0 ± 4.5 ng/mg·cr) (p < 0.05). Plasma IL-8 during relapse was significantly increased compared to that during remission(1.19 ± 0.62 vs. 0.51 ± 0.42 ng/ml) (p < 0.05). However, the negative results were obtained in the permeability assay using the Millicell system. No difference was seen in BM HSPG gene expression and HS synthesis in the GECs. Conclusion: Therefore, it seems that both IL-8 and TNF-α may not play a disease-specific role in the pathogenesis of MCD.
Architectural Hermeneutics V
Authors: Thompson Bill (William) J.
Published: July 2003

The Harry in this essay is Harry Heft, and the philosopher's stone is a contemporary reference to philosophy's problems with materialism. In his recently published work, Heft supported ecological psychology and with it Gibson's ecological perception and Barker's ecological environment, which he synthesized into an ecological psychology. Three objections arise in pursuit of Heft's synthesis. Are Gibson's affordances connected to spatial presence, or are they epiphenomena? Is Barker's ecological environment a spatial relationship or a “mental picture”? And is the human life world a spatial or phenomenological presence? This essay reviews Heft's book by way of examining those three objections raising contemporary evidence from research into cognitive science and consciousness, which Harry left out. The conclusion is that there is every reason why ecological psychology should flourish, but it is necessary to include within that “model” a more mathematical and scientific notion of materialism.
Personal Space in Physically Abused Children
Authors: Vranic Andrea
Published: July 2003

Personal space of physically abused children ( N = 36) and nonabused children ( N = 38) ages 7 to 9 was assessed using a stop-distance technique. All children were approached by female and male experimenters from four directions. The personal space of abused children is significantly larger than that of their nonabused peers. Boys and girls do not significantly differ in the preferred size of personal space. The personal space of abused children is significantly larger when approached by a male person. Such effect is not found in the control group. Interaction of Sex of Participant × Sex of Approaching Person yields significant results only when children are approached frontally, and this significance can be observed in both participant groups. In all, abused children, presumably due to their traumatic experiences, demonstrate stronger need for personal space. The author finds these results to be consistent with the protective function of personal space.
Here Comes the Dot Force!
Authors: Shade Leslie Regan
Published: July 2003

This article examines the DOT Force, a G8 initiative that aims to bridge the digital divide in developing countries. The DOT Force, announced in Summer 2000, has culminated in a set of recommendations released at the G8 meeting in Genoa in 2001. After a brief overview of the DOT Force objectives and the `Genoa Plan of Action', this article looks at the role of ICTs in development, the role of the World Trade Organization in fostering telecommunications reform in developing countries and concludes with suggestions for a more open process for consultation of the role of ICTs in development.
Reporting on Globalization
Authors: Kim Sung Tae , Weaver David H.
Published: July 2003

This article is a comparative study of news sources used in five countries facing vastly different economic circumstances. Based on a content analysis of newspaper coverage of the 1997 Asian economic crisis and the IMF bailout, sourcing patterns in US newspapers were compared to those of three Asian countries that received assistance from the IMF - Korea, Indonesia and Thailand - and those of Malaysia, which refused to accept this assistance. The findings are discussed in relation to globalization and neoliberal news frames, as well as to the indexing hypothesis and journalistic norms.
Contrasts in the Coverage of Korea and Japan by US Television Networks
Authors: Park Jowon
Published: July 2003

The present article examines the frames utilized in the US television news coverage of Korea and Japan. The research question was how American television news stories frame Korea and Japan. The study performed frame analysis of the videotaped news stories with following topics: International relations with the USA; Economics; Demonstrations and protests; and Disasters. News stories about the two countries' political relations with the USA generally utilized a cooperative frame. However, the Japanese economy was heavily framed as a rival, while Koream economy was generally framed as cooperative. The demonstration and protest stories showed a clear contrast between Korea and Japan. While networks framed demonstrations and protests in Korea in a chaos frame, they framed the majority of stories about demonstrations and protests in Japan in a democracy frame. The frame analysis of disaster stories showed a dominance of a sympathetic frame for both countries.
Unbounded Irrationality: Risk and Organizational Narcissism at Long Term Capital Management
Authors: Stein Mark
Published: July 2003

This article focuses on the near collapse of the highly prestigious hedge-fund Long Term Capital Management (LTCM) in September 1998, causing widespread fears that its demise may lead to global financial meltdown. Explanations pivoting on the idea of bounded rationality - that rationally functioning organizations may collapse because of a lack of information or the capacity to process such information - are found not to apply. The article postulates the irrational functioning of LTCM, and proposes a psychoanalytic theory of organizational narcissism as a means of explanation. This theory comprises well-explored themes of organizational narcissism such as hubris, omnipotence and omniscience, as well as newer themes of contempt, triumph, and the embeddedness of narcissism in the organization's socio-technical system. The article concludes by examining these ideas in relation to other theories of risk as well as the implications for practice.
A Narratological Approach to Understanding Processes of Organizing in a UK Hospital
Authors: Currie Graeme , Brown Andrew D.
Published: July 2003

This article outlines a narratological approach to understanding how middle managers and senior managers in a UK National Health Service (NHS) hospital made sense of the introduction of a series of interventions, led by senior managers. The research contribution this article makes is fourfold. First, it illustrates the role of individual and group narratives in processes of collective sensemaking. Second, it discusses the importance of work narratives in the efforts of individuals and groups to define their shared identities. Third, it outlines a view of organizations as storytelling milieux in which group narratives play important hegemonic and legitimatory roles. Finally, our focus on narratives, and the plurivocal understandings of actions and events they often encompass, is, we maintain, one useful means by which polysemy can be read back into case study research.
Psycho-Political Correlates of Political Efficacy
Authors: Wu Chung-Li
Published: July 2003

The sense of political efficacy is a primary orientation and an important component in studies of individual attitude sets, and it has been regarded almost exclusively as an explaining variable, rather than an explained variable. By using panel survey data of the 1994 New Orleans mayoral election, this study examined the association between political efficacy and individual-level variables, consisting of objective sociodemographic and subjective cognitive variables. The findings reveal that an individual's evaluation of government responsiveness exerts an important influence on one's sense of efficacy to affect the political world. As was true of the socio-economic status indexes, increases of education level and income are positively associated with the increasing level of political efficacy. Contrary to expectations, the findings demonstrate that race just keeps a conditional connection with feelings of efficacy.
African American Culture and Physical Skill Development Programs
Authors: Roberson Venita
Published: July 2003

What has been lacking is a rationale for professional trainers to employ African American cultural ideas to the training field. This article examines the root causes of the slow rate of change in the way professional trainers in traditionally White mainstream athletics have approached the pedagogical aspect of their work. Because many African Americans and Latinos are now entering fields that were once the preserve of the White male and female, it is important that we explore the nature of this particular asymmetrical relationship.
A Comparison of European and African-Based Psychologies and Their Implications for African American College Student Development
Authors: Johnson Vanessa D.
Published: July 2003

This article considers the appropriateness of applying college student development theories that are based on European/European American psychology to the development of African American college students. It suggests that theories for the development of African American college students should be Afrocentric in nature, that is, they should be based on African psychology.