bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Protein Kinase C in Substance P-Induced Synaptic Depression in the Nucleus Accumbens in vitro
Authors: Matowe W.C. , Ananthalakshmi K.V.V. , Kombian S.B.
Published: February 2007

Objectives: This study set out to determine the roles of protein kinase A (PKA) and protein kinase C (PKC) signalling cascades in substance P- (SP-) mediated synaptic depression in the nucleus accumbens. Materials and Methods: We used whole-cell patch recording in rat forebrain slices to study the effects of excitatory and inhibitory modulators of PKA and PKC to determine their effects on SP-induced synaptic depression. Results: We showed that cAMP and PKC, but not PKA, are involved in SP-induced synaptic depression. Bath application of SP (1 µM) depressed evoked excitatory postsynaptic currents (EPSCs) by –27.50 ± 5.6% (n = 8). Pretreatment of slices with 10 µM forskolin or rolipram prevented SP (1 µM) from depressing evoked EPSCs (–0.8 ± 6.7%, n = 6; p > 0.05 and 1.6 ± 5.6%, n = 8; p > 0.05, respectively). Furthermore, 8-bromo cAMP (1 mM) also blocked the effect of SP (–0.5 ± 14.8, n = 4, p > 0.05). However, H-89 (1 µM) did not block the SP-induced synaptic depression (–32.3 ± 4.0%, n = 4, p < 0.05). By contrast, PKC inhibitors bisindolylmaleimide (1 µM; 4.0 ± 5.1%, n = 6; p > 0.05) and calphostin C (400 nM; –6.7 ± 6.5%, n = 4, p > 0.05) both blocked SP-induced synaptic depression. Phorbol dibutyrate caused a synaptic depression of –33.0. ± 5.0% and abolished the effect of SP (1 µM, –5.9 ± 8.6%, n = 4, p > 0.05). Conclusion: Our findings demonstrate that PKC and cAMP are involved in SP-induced synaptic depression while PKA is apparently not involved. Involvement of multiple signalling pathways may reflect the fact that SP uses several intermediates to depress EPSCs.
Drug Information Resources at Private Community Pharmacies in Kuwait
Authors: Ball Douglas E. , Al-Othman Fatma
Published: February 2007

Objective: To investigate the drug information resources available in private community pharmacies in Kuwait. Materials and Methods: Pharmacists at a sample of 20 private community (retail) pharmacies completed a self-administered questionnaire of available information resources and perceived appropriate information resources to answer five drug information questions. Results: All pharmacies had at least one reference book but they were outdated. The Middle East Medical Index was most commonly found and three pharmacies had internet access. Half of the respondents reported getting medicines information directly from the pharmaceutical companies, usually through pharmaceutical representatives. Most pharmacists could identify appropriate information resources for drug dosing and drug interactions but did not fare well for medicine identification and primary research evidence. Conclusion: The poor quality and outdated drug information resources in private community pharmacies will affect the quality of information provided to clients and prescribers and have an adverse effect on the role pharmacists can play in the health system in Kuwait.
Insulin Resistance in Women with Recurrent Spontaneous Miscarriage of Unknown Aetiology
Authors: Diejomaoh Michael , Jirous Jiri , Al-Azemi Majedah , Gupta Madhu , Al-Jaber Manal , Farhat Rasheeda , Mohd Asiya
Published: February 2007

Objective: The objective of this study was to explore the role of insulin resistance in women with recurrent spontaneous miscarriage (RSM). Patients with ≧3 consecutive spontaneous miscarriages were classified as having RSM. Subjects and Methods: Thirty-five non-pregnant women presenting with RSM in our specialized RSM clinic constituted the study population, while 30 non-pregnant, parous, fertile women without RSM served as controls. The study and control patients were matched for age, ethnicity and body mass index (BMI). Blood was extracted from these patients for fasting blood glucose and fasting insulin simultaneously, and a battery of investigations including ultrasonography was performed on all the patients with RSM. Results: There was no significant difference in the mean fasting glucose for the study and control patients (5.5 ± 0.7 vs. 5.3 ± 0.6 mmol/dl) and in the mean fasting insulin (15.0 ± 5.1 and 12.9 ± 2.9 mU/l). There was a significant difference between the mean parity of the study and control patients (0.7 ± 0.7 vs. 1.7 ± 0.5, p < 0.0001) and also the mean number of miscarriages (4.2 ± 1.2 vs. 0.1 ± 0.4, p < 0.0001). There was, however, no significant difference in the insulin resistance of both groups as calculated using the Homeostasis Model Assessment and the fasting glucose insulin ratio of <4.5. Conclusion: Insulin resistance was not significantly associated with RSM in our study. Further studies may be needed.
The Antinociceptive Action of Aqueous Extract from Muntingia calabura Leaves: The Role of Opioid Receptors
Authors: Zakaria Zainul Amiruddin , Mustapha Safarul , Sulaiman Mohd. Roslan , Mat Jais Abdul Manan , Somchit Muhammad Nazrul , Abdullah Fatimah Corazon
Published: February 2007

Objective: The present study was carried out to investigate the antinociceptive activity of the aqueous extract of Muntingia calabura (MCAE) leaves and to determine the effect of temperature and the involvement of the opioid receptor on the said activity using the abdominal constriction test (ACT) and hot-plate test (HPT) in mice. Materials and Methods: The extract was prepared by soaking the dried powdered leaves of M. calabura in distilled water (dH2O) overnight, and the supernatant obtained was considered as a stock solution with 100% concentration. The stock solution was diluted to 1, 5, 10, 50 and 100% and used to determine the antinociceptive activity of MCAE. A further experiment was done with 50% concentration to determine the effect of temperature and naloxone involvement of the opioid receptor system in MCAE antinociceptive activity. Results: At the various concentrations MCAE showed significant antinociceptive activity in both tests. However, the concentration-dependent activity was observed only in the ACT but not in the HPT. The 50% concentration of MCAEs were also stable against the effect of various temperatures as indicated by the presence of activity in both tests. The temperatures (40, 60 and 100°C) also showed an enhanced extract activity only in the HPT. Pre-treatment with naloxone (2 and 10 mg/kg) blocked the extract activity in both tests, indicating the involvement of the opioid receptor system in MCAE antinociceptive activity. Conclusion: Our data indicate that M. calabura leaves possess antinociceptive activity against chemically and thermally induced noxious stimuli. The bioactive compound(s) responsible for its antinociceptive activity is/are heat-stable and work partly via the opioid receptor system.
Increased Levels of Nitric Oxide, Cortisol and Adrenomedullin in Patients with Chronic Schizophrenia
Authors: Yılmaz Necat , Herken Hasan , Cicek Hülya Kanbur , Celik Ahmet , Yürekli Muhittin , Akyol Ömer
Published: February 2007

Objective: To investigate the levels of serum cortisol, dehydroepiandrosterone sulfate (DHEA-S), nitric oxide (NO) and adrenomedullin (AM) in schizophrenic patients. Subjects and Methods: Sixty-six male patients with chronic schizophrenia and 28 normal male subjects participated in this study. The duration of disease was 145 ± 120 (mean ± SD) months. Serum levels of cortisol and DHEA-S were measured by electrochemiluminescence; plasma nitrite levels as an index of NO were measured with the Griess reaction, while plasma AM concentration was measured by using high-performance liquid chromatography. Results: Patients (12.48 ± 3.2 µg/dl), as compared to controls (10.31 ± 3.1 µg/dl), had higher levels of baseline cortisol (p < 0.05). DHEA-S levels were lower in patients though this did not reach statistical significance (302 ± 156 µg/dl compared to control, 322 ± 96 µg/dl, p > 0.05). The mean levels of plasma AM and NO in the schizophrenic group (44.33 ± 5.07 pmol/l and 36.27 ± 17.6 µmol/l) were significantly higher than the levels in the control group (14.56 ± 4.03 pmol/l and 32.54 ± 7.14 µmol/l; p < 0.001, p < 0.03, respectively). There was a positive association between duration of disease and cortisol/DHEA-S ratio and cortisol level. Conclusion: The data show that schizophrenia is associated with abnormal levels of cortisol, DHEA-S, NO and AM.
Idiopathic Hypertrophic Pyloric Stenosis Combined with Left Paraduodenal Hernia in an Adult
Authors: Papaziogas Basilios , Lazaridis Charalambos , Souparis Anastasios , Koutelidakis Ioannis , Grigoriou Marios , Dragoumis Dimitris , Atmatzidis Konstantinos
Published: February 2007

Objective: We report a case of primary hypertrophic pyloric stenosis combined with a paraduodenal hernia in a 35-year-old woman. Clinical Presentation and Intervention: The patient presented with signs of obstructive ileus. CT of the abdomen revealed a marked dilatation of the stomach and the proximal jejunum as well as a circumferential thickening of the antral-pyloric region with characteristics indicating hypertrophic pyloric stenosis. Exploratory laparotomy revealed the presence of a paraduodenal hernia containing jejunal loops and marked thickening of the pyloric region. The jejunum was reduced to its normal place and the ostium of the paraduodenal hernia closed with a running suture. The hypertrophic pyloric stenosis was treated with pyloromyotomy. Since the patient had no predisposing factors for the development of secondary pyloric stenosis, we considered the pyloric stenosis as congenital in origin. Conclusion: To our knowledge this is the first reported case of congenital pyloric stenosis combined with the presence of a paraduodenal hernia in an adult.
Immunohistochemical Organization of the Forebrain in the White Sturgeon, Acipenser transmontanus
Authors: Piñuela Carmen , Northcutt R. Glenn
Published: February 2007

The distribution of substance P (SP), leucine-enkephalin (LENK), serotonin (5HT), dopamine (DA), and tyrosine hydroxylase (TH) was examined in the forebrain of the white sturgeon in order to evaluate several anatomical hypotheses based on cytoarchitectonics, and to gain a better understanding of the evolution of the forebrain in ray-finned fishes. The subpallium of the telencephalon has the highest concentration of the neuropeptides SP and LENK, allowing the pallial-subpallial border to be easily distinguished. The distribution of dopamine is similar to that of serotonin in the subpallium, fibers positive for these transmitters are particularly dense in the dorsal and ventral divisions of the subpallium. In addition, a small population of DA- and 5HT-positive cell bodies – which appear to be unique to sturgeons – was identified at the level of the anterior commissure. The internal granular layer of the olfactory bulbs had large numbers of TH-positive cell bodies and fibers, as did the rostral subpallium. The occurrence of cell bodies positive for LENK in the dorsal nucleus of the rostral subpallium supports the hypothesis that this nucleus is homologous to the striatum in other vertebrates. This is further reinforced by the apparent origin of an ascending dopaminergic pathway from cells in the posterior tubercle that are likely homologous to the ventral tegmental area/substantia nigra in land vertebrates. Finally, the differential distribution of SP and TH in the pallium supports the hypothesis that the pallium, or area dorsalis, can be divided medially into a rostral division (Dm), a caudal division (Dp) that is the main pallial target of secondary olfactory projections, and a narrow lateral division (Dd+Dl) immediately adjacent to the attachment of the tela choroidea along the entire rostrocaudal length of the telencephalic hemisphere.
Greater Impairment of Ability in the Divided Attention Task Is Seen in Alzheimer’s Disease Patients with Depression than in Those without Depression
Authors: Nakaaki Shutaro , Murata Yoshie , Sato Junko , Shinagawa Yoshihiro , Tatsumi Hiroshi , Hirono Nobutsugu , Furukawa Toshiaki A.
Published: February 2007

Background: Recent studies have emphasized specific deficits of attention and executive functions, such as those of cognitive flexibility, divided attention, in geriatric patients with depression. In Alzheimer’s disease (AD), depressive symptoms are known to occur even from an early stage of the disease. However, the nature of the impairment of executive functions in depression associated with AD remains unclear, because of the frequent occurrence of the apathy syndrome as a major confounding factor. Method: In this study, we conducted a comprehensive comparative neuropsychological assessment in AD patients with (n = 21) and without (n = 21) depression. The diagnosis of depression was based on provisional criteria proposed by Olin’s group. Results: In terms of apathy symptoms, both groups had a similar degree of deficits, which were mild as assessed according to Neuropsychiatric Inventory criteria. While no significant differences were observed in regard to the scores in general intellectual functioning, episodic memory and some attention and executive tasks between the two groups, AD patients with depression showed significantly lower scores in several attention and executive function tasks, such as the dual-task performance task administered to assess the capacity for divided attention, and the cognitive flexibility (Trail Making Test; Part B), than AD patients without depression. Conclusions: Our results suggest that depressive symptoms in AD patients increase the deficits of cognitive flexibility and divided attention. This is the first study to report a correlation between depressions, diagnosed based on the provisional criteria for depression in AD by Olin’s group, and an impaired capacity for divided attention in AD patients.
HFE Gene Mutations and Oxidative Stress Influence Serum Ferritin, Associated with Vascular Damage, in Hemodialysis Patients
Authors: Valenti Luca , Valenti Gianfranco , Como Giovanna , Burdick Larry , Santorelli Gennaro , Dongiovanni Paola , Rametta Raffaela , Bamonti Fabrizia , Novembrino Cristina , Fracanzani Anna Ludovica , Messa Pier Giorgio , Fargion Silvia
Published: February 2007

Background/Aims: Hyperferritinemia has been associated with cardiovascular mortality in hemodialysis patients. The aim of this study was to evaluate whether serum ferritin was affected by iron and oxidative status and by genetic factors (HFE mutations and the Ala9Val MnSOD polymorphism), and to assess the association between ferritin and cardiovascular damage evaluated by ecocolor-Doppler. Methods: 63 hemodialysis patients were tested for HFE and MnSOD genotype by restriction analysis and oxidative status; vascular damage was assessed by measuring intima-media thickness, and by detecting plaques at carotid and femoral arteries. Results: Ferritin was correlated with transferrin saturation (p = 0.003), decreased iron-specific serum antioxidant activity (p = 0.01), age (p = 0.03), and C282Y and H63D HFE mutations (p = 0.05), but not with the MnSOD polymorphism. Ferritin was associated with advanced vascular damage, as evaluated by the presence of plaques, both at carotid (p = 0.03) and femoral arteries (p = 0.001), the other risk factors being age and low albumin. Low iron-specific antioxidant activity was associated with carotid plaques (p = 0.03). Conclusion: In hemodialysis patients, hyperferritinemia reflects a relative increase in iron availability and a decrease in iron-specific antioxidant activity, is favored by HFE mutations, and represents a risk factor for advanced cardiovascular damage.
Normal Anatomy and Physiology of the Spinal Cord Dorsal Horn
Authors: Light Alan R.
Published: February 2007

The dorsal horn of the spinal cord receives afferent input from innocuous primary afferent neurons via collaterals from the dorsal columns. This input is integrated and relayed primarily by neurons in laminae III-VI. Dorsal horn neurons which encode innocuous inputs project to the medulla and the cervical spinal cord via the dorsal columns and the dorsolateral funiculus. Nociceptive primary afferent neurons enter the spinal dorsal horn via collaterals from Lissauer’s tract. Nociceptive input is integrated and relayed by neurons in laminae I, II and V which project to the reticular formation and thalamus via the anterolateral tract.
Neurochemistry of the Dorsal Horn
Authors: Blumenkopf Bennett
Published: February 2007

The dorsal horn region of the spinal cord, particularly the dorsal root entry zone (DREZ), represents the first central integration center for nociceptive afferent impulses. Here, the excitatory neurotransmitters/modulators, products of the primary sensory neurons, are released, the segmental interneuronal influences pertain, and the descending bulbospinal tracts terminate. A vast variety of compounds are thus involved in the processing of nociceptive information in these areas, among which are the ‘classical’ neurotransmitters and the more recently described neuropeptides. A continued vast interest exists concerning the chemistry of the dorsal horn/DREZ region. The current developments and understanding regarding the pharmacology of this region are presented. Particular emphasis is given to the interactions among the various compounds, the coexistence of some of these within single neuronal populations, the importance of the opiate receptor subtypes, and the actions and localizations of some of the newly discovered neuropeptides.
Abnormal Physiology of the Dorsal Horn As Related to the Deafferentation Syndrome
Authors: Ovelmen-Levitt Janice
Published: February 2007

The spinal cord dorsal horn has been implicated in the generation of pain and dysesthesias following nerve and nerve root damage and/or avulsion, as well as following damage in adjacent spinal cord regions. Alterations in the functional properties of dorsal horn neurons occur after deafferentation and may underlie the occurrence of abnormal sensations referred to the denervated body part. Abnormal activity following deafferentation has also been noted at thalamic and cortical levels. Some of these post-denervation functional changes, determined anatomically and/or electrophysiologically, are reviewed as well as the results of behavioral studies of the deafferentation syndrome in the rat.
Deafferentation Pain in Man
Authors: Sweet William H.
Published: February 2007

Pains of various etiologies are described in so many overlapping ways that verbal descriptions alone do not permit a valid distinction between those pains associated with neurological injury (with or without sensory loss) and those associated with neurological compression. Nor does the fact of some sensory loss plus pain constitute a useful classification to determine either the mechanism of the pain or its treatment. Progress is more likely to ensue if we seek to characterize in detail each type of painful lesion. Evidence for these conclusions is drawn from cases of brachial plexus injury, trigeminal rhizotomy and tractotomy, postcordotomy dysesthesia and central pain treated by regional guanethidine block. Examples of the value of totally innovative approaches are drawn from the physics of elementary particles.
Experimental Deafferentation Syndromes
Authors: Levitt M.
Published: February 2007

Animal models of dysesthesias have been established, and reveal the following major points. Dysesthesias of peripheral nerve or dorsal root origin have a central neural cause. Chronic dysesthesias of spinal origin have a cause which resides in the brain. The origins of these effects are lesions in the spinothalamic system. The causes of these effects are abnormal functionings among opiate, catecholamine, and purine pathways. Denervation supersensitivity is suggested.
Intraoperative Somatosensory Evoked Potentials
Authors: Makachinas Thad , Ovelmen-Levitt Janice , Nashold Jr. Blaine S.
Published: February 2007

The localization of neural pathology by the evoked potential technique through the use of the Nicolet compact four-signal averager is reviewed. Stimulating electrode application on facial nerves and peripheral nerves of the limbs is described, as well as spinal cord and medullary recording electrode type and placement. Several pathological lesions causing pain are presented and the intraoperative evoked potentials prior to and after lesion production are examined and analyzed.
Lesions of Spinal and Trigeminal Dorsal Root Entry Zone for Deafferentation Pain
Authors: Ishijima Buichi , Shimoji Koki , Shimizu Hiroyuki , Takahashi Hiroshi , Suzuki Ichiro
Published: February 2007

Spinal and trigeminal dorsal root entry zone destruction (DREZ-tomy) was performed on 35 patients with deafferentation pain of various types. Overall, satisfactory pain relief was obtained in 65.5% of spinal DREZ-tomy cases in the follow-up observation. The result in the brachial plexus avulsion group was the best (82.4% improved), followed by the limb pain group without root avulsion (50.0%), but the truncal or visceral pain group showed the worst result (33.3%). Two patients with postherpetic trigeminal neuralgia were completely relieved of pain in the average follow-up period of 32 months, while in 2 patients with postrhizotomy facial pain, pain recurred 4 months after the operation in 1, and, in the other, pain in the medial part of the face remained unchanged. Complications were seen in about 60% of the patients, which were, however, all mild, except for 2 cases of death due to gastrointestinal disease.
Anatomic Examination of Human Dorsal Root Entry Zone Lesions
Authors: Iacono R.P. , Aguirre M.L. , Nashold Jr. B.S.
Published: February 2007

The anatomic delineation of radiofrequency dorsal root entry zone lesions using the Nashold thermocouple electrode is presented. The sharply delineated lesions involve a major portion of the dorsal horn of the spinal cord including Rexed’s lamina V and part of VI. The extent of these lesions is appropriate, based on the currently understood mechanisms of spinal generators of chronic deafferentation pain.
Radiofrequency Lesion Generation and lts Effect on Tissue Impedance
Authors: Cosman Eric R. , Rittman William J. , Nashold Blaine S. , Makachinas Thad T.
Published: February 2007

The method of radiofrequency heat lesion generation is reviewed with specific reference to the dorsal root entry zone. Experimental data on the impedance of electrolytic media as a function of temperature are reported, and their relation to what should be observed during radiofrequency lesioning in the body is commented upon. The future utility of impedance monitoring is discussed as well as possible implications of bipolar lesion electrode systems.
Pain Control with Laser-Produced Dorsal Root Entry Zone Lesions
Authors: Powers Stephen K. , Barbaro Nicholas M. , Levy Robert M.
Published: February 2007

Pain relief was evaluated in 40 patients with various types of deafferentation pain that were treated with dorsal root entry zone (DREZ) lesions produced with microsurgical lasers. Good long-term pain relief was evident in some paraplegics and in all patients with brachial plexus avulsion. Several other small subgroups of patients benefited from laser DREZ lesions as well. Pain associated with arachnoiditis and peripheral nerve injury or neuropathy did not respond to laser DREZ lesioning. Based upon the smaller lesion dimensions produced with the lasers, it is proposed that interruption of impulses in the tract of Lissauer may be a mechanism of pain control in patients that responded to laser DREZ lesions.
Evaluation of Laser- and Radiofrequency-Generated Dorsal Root Entry Zone Lesions in the Cat
Authors: Elias Zev , Powers Stephen K. , Bullitt Elizabeth
Published: February 2007

The current study was designed to measure and compare the size of dorsal root entry zone lesions made in the midthoracic spinal cord of anesthetized cats with a carbon dioxide laser and the radiofrequency (RF) probe utilizing currently employed clinical parameters. Cats were monitored intraoperatively with somatosensory evoked potentials (SSEPs) derived from stimulation of the ipsilateral posterior tibial nerve in order to assess the acute effect of lesion production on function within the ipsilateral dorsal column. Daily postoperative neurologic evaluations were recorded. The lesioned segments of spinal cord from sacrificed animals were examined histologically to determine the extent of cord injury at 1 and 30 days. SSEPs remained normal for the laser group, but were uniformly attenuated or lost in the RF group. Neurologically, the laser group fared better, with only a mild transient monoparesis, compared to a persistent moderate paraparesis for the RF group. On histologic examination, the depths of the laser and electrode lesions were similar, but the RF lesions showed more lateral spread. Laser lesions comprised 4.4 ± 1.6% of the cross-sectional area of the spinal cord whereas the RF lesions occupied 22.8 ± 4%. These findings demonstrate that at the parameters employed, the carbon dioxide laser produces smaller lesions than does the RF electrode.
The Geographic Distribution of Big Five Personality Traits
Authors: Schmitt David P. , Allik Jüri , McCrae Robert R. , Benet-Martínez Verónica
Published: February 2007

The Big Five Inventory (BFI) is a self-report measure designed to assess the high-order personality traits of Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness. As part of the International Sexuality Description Project, the BFI was translated from English into 28 languages and administered to 17,837 individuals from 56 nations. The resulting cross-cultural data set was used to address three main questions: Does the factor structure of the English BFI fully replicate across cultures? How valid are the BFI trait profiles of individual nations? And how are personality traits distributed throughout the world? The five-dimensional structure was robust across major regions of the world. Trait levels were related in predictable ways to self-esteem, sociosexuality, and national personality profiles. People from the geographic regions of South America and East Asia were significantly different in openness from those inhabiting other world regions. The discussion focuses on limitations of the current data set and important directions for future research.
Measuring Cultures through Intersubjective Cultural Norms
Authors: Wan Ching , Chiu Chi-Yue , Peng Siqing , Tam Kim-Pong
Published: February 2007

Core values of a culture may refer to values endorsed by most members of the culture or to values members of the culture generally believe to be widely shared in the culture. The authors propose an intersubjective consensus approach to identifying core cultural values based on the latter definition. In three studies, they illustrated the utility of the intersubjective consensus approach for identifying the cultural values that differentiate two or more nested cultural groups. They showed that endorsement of these values was related to the relative strength of identification with these cultural groups. The findings from the present research have important implications for social identity theories and acculturation research.
T cell–dependent survival of CD20+ and CD20− plasma cells in human secondary lymphoid tissue
Authors: Withers David R. , Fiorini Claudia , Fischer Randy T. , Ettinger Rachel , Lipsky Peter E. , Grammer Amrie C.
Published: February 2007

The signals mediating human plasma cell survival in vivo, particularly within secondary lymphoid tissue, are unclear. Human tonsils grafted into immunodeficient mice were therefore used to delineate the mechanisms promoting the survival of plasma cells. Tonsillar plasma cells were maintained within the grafts and the majority were nonproliferating, indicating a long-lived phenotype. A significant depletion of graft plasma cells was observed after anti-CD20 treatment, consistent with the expression of CD20 by most of the cells. Moreover, anti-CD52 treatment caused the complete loss of all graft lymphocytes, including plasma cells. Unexpectedly, anti-CD3, but not anti-CD154, treatment caused the complete loss of plasma cells, indicating an essential role for T cells, but not CD40-CD154 interactions in plasma cell survival. The in vitro coculture of purified tonsillar plasma cells and T cells revealed a T-cell survival signal requiring cell contact. Furthermore, immunofluorescence studies detected a close association between human plasma cells and T cells in vivo. These data reveal that human tonsil contains long-lived plasma cells, the majority of which express CD20 and can be deleted with anti-CD20 therapy. In addition, an important role for contact-dependent interactions with T cells in human plasma cell survival within secondary lymphoid tissue was identified.
Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study
Authors: Hasle Henrik , Alonzo Todd A. , Auvrignon Anne , Behar Catherine , Chang Myron , Creutzig Ursula , Fischer Alexandra , Forestier Erik , Fynn Alcira , Haas Oskar A. , Harbott Jochen , Harrison Christine J. , Heerema Nyla A. , van den Heuvel-Eibrink Marry M. , Kaspers Gertjan J. L. , Locatelli Franco , Noellke Peter , Polychronopoulou Sophia , Ravindranath Yaddanapudi , Razzouk Bassem , Reinhardt Dirk , Savva Natalia N. , Stark Batia , Suciu Stefan , Tsukimoto Ichiro , Webb David K. , Wojcik Dorora , Woods William G. , Zimmermann Martin , Niemeyer Charlotte M. , Raimondi Susana C.
Published: February 2007

Monosomy 7 (−7) and deletion 7q \del(7q)] are rare in childhood acute myeloid leukemia (AML). We retrospectively collected data on 258 children with AML or refractory anemia with excess blasts in transformation (RAEB-T) and −7 or del(7q) with or without other cytogenetic aberrations \± other]. Karyotypes included −7 (n = 90), −7 other (n = 82), del(7q) (n = 21), and del(7q) other (n = 65). Complete remission (CR) was achieved in fewer patients with −7 ± other compared with del(7q) ± other (61% versus 89%, P < .001). Overall, the 5-year survival rate was 39% (SE, 3%). Survival was superior in del(7q) ± other compared with −7 ± other (51% versus 30%, P < .01). Cytogenetic aberrations considered favorable in AML \t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q22;q21), t(9;11)(p22;q23)] (n = 24) were strongly associated with del(7q) and a higher 5-year survival rate compared with del(7q) without favorable cytogenetics (75% versus 46%, P = .03). Patients with −7 and inv(3),−5/del(5q), or + 21 had a 5-year survival rate of 5%. Stem cell transplantation analyzed as a time-dependent variable had no impact on overall survival. However, patients not achieving CR had a 31% survival rate after stem cell transplantation. Childhood AML with chromosome 7 aberrations represents a heterogeneous group of disorders with additional cytogenetic aberrations having a major prognostic impact which should be reflected in future risk-group stratification.
Bortezomib enhances dendritic cell (DC)–mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications
Authors: Spisek Radek , Charalambous Anna , Mazumder Amitabha , Vesole David H. , Jagannath Sundar , Dhodapkar Madhav V.
Published: February 2007

Most anticancer chemotherapies are immunosuppressive and induce nonimmunogenic tumor cell death. Bortezomib, a specific inhibitor of 26S proteasome, has shown clinical activity in several human tumors, including myeloma. Here we show that the uptake of human myeloma cells by dendritic cells (DCs) after tumor cell death by bortezomib, but not γ irradiation or steroids, leads to the induction of antitumor immunity, including against primary tumor cells, without the need for any additional adjuvants. The delivery of activating signal from bortezomib-killed tumor cells to DCs depends on cell-cell contact between DCs and dying tumor cells and is mediated by bortezomib-induced exposure of heat shock protein 90 (hsp90) on the surface of dying cells. The combination of bortezomib and geldanamycin (an hsp90 inhibitor) leads to greater apoptosis of tumor cells but abrogates their immunogenicity. These data identify drug-induced exposure of endogenous heat shock proteins on the surface of dying cells as a mechanism of immunogenic death of human tumors. Specific targeting of bortezomib to tumors may enhance their immunogenicity and the induction of antitumor immunity.
Black tea prevents cigarette smoke-induced apoptosis and lung damage
Authors: Banerjee Shuvojit , Maity Palas , Mukherjee Subhendu , Sil Alok K , Panda Koustubh , Chattopadhyay Dhrubajyoti , Chatterjee Indu B
Published: February 2007

Background

Cigarette smoking is a major cause of lung damage. One prominent deleterious effect of cigarette smoke is oxidative stress. Oxidative stress may lead to apoptosis and lung injury. Since black tea has antioxidant property, we examined the preventive effect of black tea on cigarette smoke-induced oxidative damage, apoptosis and lung injury in a guinea pig model.

Methods

Guinea pigs were subjected to cigarette smoke exposure from five cigarettes (two puffs/cigarette) per guinea pig/day for seven days and given water or black tea to drink. Sham control guinea pigs were exposed to air instead of cigarette smoke. Lung damage, as evidenced by inflammation and increased air space, was assessed by histology and morphometric analysis. Protein oxidation was measured through oxyblot analysis of dinitrophenylhydrazone derivatives of the protein carbonyls of the oxidized proteins. Apoptosis was evidenced by the fragmentation of DNA using TUNEL assay, activation of caspase 3, phosphorylation of p53 as well as over-expression of Bax by immunoblot analyses.

Results

Cigarette smoke exposure to a guinea pig model caused lung damage. It appeared that oxidative stress was the initial event, which was followed by inflammation, apoptosis and lung injury. All these pathophysiological events were prevented when the cigarette smoke-exposed guinea pigs were given black tea infusion as the drink instead of water.

Conclusion

Cigarette smoke exposure to a guinea pig model causes oxidative damage, inflammation, apoptosis and lung injury that are prevented by supplementation of black tea.
Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 cooperatively contribute to the cutaneous Arthus reaction
Authors: Orito Hidemitsu , Fujimoto Manabu , Ishiura Nobuko , Yanaba Koichi , Matsushita Takashi , Hasegawa Minoru , Ogawa Fumihide , Takehara Kazuhiko , Sato Shinichi
Published: February 2007

Immune complex (IC)-induced inflammation is mediated by inflammatory cell infiltration, a process that is highly regulated by expression of multiple adhesion molecules. The roles and interactions of ICAM-1 and VCAM-1, the major regulators of leukocyte firm adhesion, were examined in the cutaneous reverse-passive Arthus reaction using ICAM-1-deficient (ICAM-1−/−) mice and blocking mAb against VCAM-1. Within 8 h, IC challenge of wild-type mice induced edema, hemorrhage, interstitial accumulation of neutrophils and mast cells, as well as production of TNF-α and IL-6. All of these inflammatory parameters were reduced significantly in ICAM-1−/− mice. The blockade of VCAM-1 in wild-type mice did not affect any inflammatory parameters. In contrast, ICAM-1−/− mice treated with anti-VCAM-1 mAb had significantly reduced edema, hemorrhage, and neutrophil infiltration. Furthermore, VCAM-1 blockade in ICAM-1−/− mice suppressed cutaneous TNF-α and IL-6 production. Thus, VCAM-1 plays a complementary role to ICAM-1 in the cutaneous Arthus reaction by regulating leukocyte accumulation and proinflammatory cytokine production.
Hypermethylation of Adenosine Triphosphate-Binding Cassette Transporter Genes in Primary Hyperparathyroidism and Its Effect on Sestamibi Imaging
Authors: Takeuchi Hiroya , Greep Nancy C. , Hoon Dave S. B. , Giuliano Armando E. , Hansen Nora M. , Umetani Naoyuki , Singer Frederick R.
Published: February 2007

Context: Retention of technetium-99m-sestamibi (99mTc-sestamibi) by parathyroid adenomas appears to be due to the loss of at least one membrane transporter, multidrug resistance 1 (MDR1), and possibly another, multidrug resistance-associated protein 1 (MRP1).

Objective: The objective was to determine whether hypermethylation of either gene plays a role in their expression and 99mTc-sestamibi retention.

Design: This was a retrospective study on a convenience sample of paraffin-embedded parathyroid glands.

Setting: The study was performed at the John Wayne Cancer Institute at Saint John’s Health Center (Santa Monica, CA).

Patients: Forty-eight patients with primary hyperparathyroidism and five patients without parathyroid disease undergoing thyroid surgery provided 27 adenomatous, 10 hyperplastic, and 16 normal parathyroid glands.

Intervention: We performed immunohistochemistry, real-time quantitative RT-PCR, and methylation-specific PCR for MDR1 and MRP1 on archival parathyroid tissue and correlated these results with the patient’s 99mTc-sestamibi scan.

Main Outcome Measure: The main outcome measure was to determine whether hypermethylation of the genes for either transporter is associated with loss of their expression and with a positive 99mTc-sestamibi scan.

Results: The MDR1 gene was methylated in none of 12 normal glands, 19 of 27 adenomas, and three of 10 hyperplastic glands. Methylation of the MRP1 gene was uncommon (five of 48 tested glands). Methylation of the gene affected the transcript level only for MDR1. Among all glands, hypermethylation for MDR1 was more likely in 99mTc-sestamibi-positive scans (P < 0.001).

Conclusion: In parathyroid tissue, hypermethylation of the MDR1 gene decreases its expression and is associated with increased detection of parathyroid adenomas by 99mTc-sestamibi parathyroid scans.
Meiotic interference among MLH1 foci requires neither an intact axial element structure nor full synapsis
Authors: de Boer Esther , Dietrich Axel J. J. , Höög Christer , Stam Piet , Heyting Christa
Published: February 2007

During meiosis, homologous chromosomes (homologs) perform reciprocal exchanges (crossovers) at a high frequency. Crossovers display interference, i.e. their spacing is more even than would be expected if they were placed randomly along the chromosomes. Concomitantly with crossover formation, synaptonemal complexes (SCs) appear between homologs: each chromosome forms an axial structure, the axial element (AE); the AEs of homologs align, and numerous transverse filaments connect the AEs to form an SC. Both the AE and the SC have been implicated in the imposition of interference. We investigated whether intact AEs or SCs are required for crossover interference in the mouse, using a mutant lacking AE protein SYCP3, which displays structurally abnormal AEs and incomplete synapsis. We estimated the level of interference from the spacing of immunofluorescent MLH1 foci, which mark almost all crossover sites in the mouse, along the SCs. The levels of interference among MLH1 foci in wild-type and Sycp3–/– mice were comparable, implying that neither an intact AE structure nor full synapsis is required for wild-type levels of interference.
Dual effects of the membrane-anchored MMP regulator RECK on chondrogenic differentiation of ATDC5 cells
Authors: Kondo Shunya , Shukunami Chisa , Morioka Yoko , Matsumoto Naoya , Takahashi Rei , Oh Junseo , Atsumi Tadao , Umezawa Akihiro , Kudo Akira , Kitayama Hitoshi , Hiraki Yuji , Noda Makoto
Published: February 2007

Extracellular matrix (ECM) undergoes continuous remodeling during mammalian development. Although involvement of matrix metalloproteinases (MMPs) in ECM degradation has been well documented, how this process is regulated to allow proper ECM accumulation remains unclear. We previously showed the involvement of a membrane-anchored MMP regulator, RECK (reversion-inducing cysteine-rich protein with Kazal motifs), in vascular development in mice. Here we report that Reck mRNA can be detected in developing cartilage in E13.5∼16.5 mouse embryos and is progressively upregulated during differentiation of a chondrogenic cell line ATDC5 in vitro. In the early phase of ATDC5 differentiation, RECK expression stays low, multiple MMPs are upregulated, and there is ECM degradation at the sites of cellular condensation. In the later phase, RECK is upregulated inside the expanding cartilaginous nodules where type II collagen is accumulated while active ECM degradation persists along the rim of the nodules. Constitutive RECK expression suppressed initial cellular condensation, whereas RECK knockdown suppressed the later ECM accumulation in the cartilaginous nodules. These results suggest that RECK expression at the right place (in the core of the nodules) and at the right time (only in the later phase) is important for proper chondrogenesis and that RECK, together with MMPs, plays a crucial role in regulating dynamic processes of tissue morphogenesis.
Sheet migration by wounded monolayers as an emergent property of single-cell dynamics
Authors: Bindschadler Michael , McGrath James L.
Published: February 2007

Multi-cell migration is important for tissue development and repair. An experimentally accessible example of multi-cell migration is provided by the classic scratch-wound assay. In this assay, a confluent monolayer is `injured' by forcibly removing a strip of cells, and the remaining monolayer `heals' through some combination of cell migration, spreading and proliferation. The scratch wound has been used for decades as a model of wound healing and an assay of cell migration, however the mechanisms that underlie the coherent expansion of cells in the surviving monolayer are still debated. Here we develop an agent-based computational model that predicts the most robust characteristics of healing in scratch wounds. The cells in our model are simple mechanical agents that respond to cell contact by redirecting migration and slowing division. We imbued model cells with crawling and growth dynamics and measured for individual L1 fibroblasts and found that simulated recovery occurs in a steady, sheet-like and division-independent fashion to mimic healing by L1s. The lack of cohesion and biochemical cell-cell communication in the model suggests that these factors are not strictly necessary for cells to migrate as a group. Instead, our analysis suggests that steady sheet migration can be explained by cell spreading in the monolayer.
China's Climate Change Positions: At a Turning Point?
Authors: Tangen Kristian , Heggelund Gørild , Buen Jørund
Published: February 2007

The purpose of this article is to discuss major concerns and perceptions underlying Chinese positions in the international climate negotiations. China has asserted that concrete action on the part of developed countries is a precondition for any developing country action. It has been sceptical of the Kyoto Mechanisms and has consistently refused to discuss quantified emission limits for developing countries. China's position regarding the Clean Development Mechanism has, however, developed from scepticism towards a more pragmatic focus on maximising benefits. The dynamics of China's positioning can partly be explained by perceptions of costs, but also ‘high politics’, and tactical considerations. However, in light of the external and internal forces for change, it is worth asking how long it will be in China's interest to stick to its present position.
US Climate Policy: Evolution and Future Prospects
Authors: Agrawala Shardul , Andresen Steinar
Published: February 2007

Climate change is a problem which US science has significantly helped to bring to the world's attention. It now requires initiatives in US domestic policy for even the first steps towards any realistic global resolution of this problem. This paper addresses three questions: (1) How has US climate policy evolved since climate change became an international political concern in the late–1980s?; (2) what is the relative significance of various factors, both domestic and international, in shaping this evolution?; and (3) what are some likely future scenarios for the climate regime and the role of the US under the new Bush (Jr.) administration? This analysis suggests that the US has generally played a cautious, even blocking role on the international arena, although the period between 1992 and 1997 witnessed a rather uneven march towards progressivism, culminating in the US agreeing to a 7% cut in its greenhouse emissions by 2008–2012 under the Kyoto Protocol. US policy during the Bush (Sr.) and Clinton administrations was primarily shaped by powerful ideologues, while a second critical determinant was the constitutional separation of powers between the executive and legislature. Scientific assessments and international negotiations meanwhile have given climate change unusual stamina on the domestic agenda, while the preferred set of policy responses has been constrained by a national culture that gives primacy to the market over the state. Looking into the future, the recent one-two punch delivered by President George W. Bush in reversing his pledge to regulate carbon dioxide followed by a rejection of US commitments under the Kyoto Protocol renders any expectation of measures to reduce domestic emissions unrealistic, and is likely to cripple the treaty in its present form. The possibility of an alternate to the Kyoto Protocol also appears very remote at this time. However, while official action is unlikely, it is possible that the growth of US greenhouse emissions might be reduced in the near future due to offsetting factors such as a widely expected economic slowdown.
Russian Climate Policies: More Than Hot Air?
Authors: Moe Arild , Tangen Kristian
Published: February 2007

The purpose of this article is to review and explain Russia's positions in the climate negotiations and point to future challenges for Russia in the climate regime. Russia appears to become a large beneficiary of the trading system created by the Kyoto Protocol. The current allocation of quotas under the protocol will probably create substantial revenues for Russia, and it could also help attract foreign investment to its poorly maintained power and industrial sectors. Russia's positions in the international negotiations have changed as these potential benefits for the country have become apparent. However, although the Kyoto regime, if it enters into force, will mean new and additional revenues for Russia, there are several factors that might prevent Russia from reaping the full benefits created by the Kyoto Protocol.
India and Climate Change Policy: Between Diplomatic Defensiveness and Industrial Transformation
Authors: Gupta Joyeeta
Published: February 2007

This article focuses on the evolution of India's climate change policy over the last decade and the key driving factors that have led to changes in the nature of this policy. It argues that although India appears to be taking a defensive position in relation to climate change in the international arena; in fact there have been a large number of measures that have been initiated since 1990 within India and these measures collectively are likely to lead to a decoupling of greenhouse gas emissions from energy development and possibly even economic growth. Nevertheless, the government is likely to adopt a cautious position in international negotiations in order to avoid taking on legally binding quantitative commitments and because of their position that the onus lies on the developed countries to take action. Thus although de facto India is taking a number of climate related no regret measures, it will be unwilling to take on de jure commitments in the short-term.