bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Aldosterone Secretion: A Model for Convergence in Cellular Signaling Pathways
Authors: SPÄT ANDRÁS , HUNYADY LÁSZLÓ
Published: March 2004

Spät, András, and László Hunyady. Control of Aldosterone Secretion: A Model for Convergence in Cellular Signaling Pathways. Physiol Rev 84: 489–539, 2004; 10.1152/physrev.00030.2003.—Aldosterone secretion by glomerulosa cells is stimulated by angiotensin II (ANG II), extracellular K+, corticotrophin, and several paracrine factors. Electrophysiological, fluorimetric, and molecular biological techniques have significantly clarified the molecular action of these stimuli. The steroidogenic effect of corticotrophin is mediated by adenylyl cyclase, whereas potassium activates voltage-operated Ca2+channels. ANG II, bound to AT1receptors, acts through the inositol 1,4,5-trisphosphate (IP3)-Ca2+/calmodulin system. All three types of IP3receptors are coexpressed, rendering a complex control of Ca2+release possible. Ca2+release is followed by both capacitative and voltage-activated Ca2+influx. ANG II inhibits the background K+channel TASK and Na+-K+-ATPase, and the ensuing depolarization activates T-type (Cav3.2) Ca2+channels. Activation of protein kinase C by diacylglcerol (DAG) inhibits aldosterone production, whereas the arachidonate released from DAG in ANG II-stimulated cells is converted by lipoxygenase to 12-hydroxyeicosatetraenoic acid, which may also induce Ca2+signaling. Feedback effects and cross-talk of signal-transducing pathways sensitize glomerulosa cells to low-intensity stimuli, such as physiological elevations of [K+] (≤1 mM), ANG II, and ACTH. Ca2+signaling is also modified by cell swelling, as well as receptor desensitization, resensitization, and downregulation. Long-term regulation of glomerulosa cells involves cell growth and proliferation and induction of steroidogenic enzymes. Ca2+, receptor, and nonreceptor tyrosine kinases and mitogen-activated kinases participate in these processes. Ca2+- and cAMP-dependent phosphorylation induce the transfer of the steroid precursor cholesterol from the cytoplasm to the inner mitochondrial membrane. Ca2+signaling, transferred into the mitochondria, stimulates the reduction of pyridine nucleotides.
Progress and Prospects for the Development of Computer Generated Actors for Military Simulation, Part 3—The Road Ahead
Authors: Stytz Martin R. , Banks Sheila B.
Published: March 2004

The development of realistic computer-generated synthetic environments, also calleddistributed virtual environments, relies heavily upon computer-generated actors (CGAs) to provide accurate behaviors at reasonable cost so that the synthetic environments are useful, affordable, complex, and high fidelity. Unfortunately, the pace of synthetic environment development and the level of desired CGA performance continue to rise at a much faster rate than CGA capability improvements. This insatiable demand for realism in CGAs for synthetic environments arises from the growing understanding of the significant role that modeling and simulation can play in a variety of uses. These uses include training, analysis, procurement decisions, mission rehearsal, doctrine development, force-level and task-level training, information assurance, cyberwarfare, force structure analysis, sustainability analysis, life cycle costs analysis, material management, infrastructure analysis, and many other uses. In these and other uses of military synthetic environments, CGAs play a central role because they have the potential to increase the realism of the environment while also reducing the cost of operating the environment. The progress made in addressing the technical challenges that must be overcome to realize effective and realistic CGAs for military simulation environments and the technical areas that should be the focus of future work are the subject of this paper, which surveys the technologies and progress made in the construction and use of CGAs. In this, the third installment in the series of papers discussing CGAs, we conclude our discussion of CGA technologies by concluding the discussion of human behavior modeling for CGAs, and we present some suggested future research directions for CGA technologies.
Strong robustness in multi‐phase adaptive control: the basic scheme
Authors: Cadic Maria , Willem Polderman Jan
Published: March 2004

The general structure of adaptive control systems based on strong robustness is introduced. This approach splits into two phases. In the first phase, emphasis is put on identification until enough information is obtained in order to design a controller that stabilizes the actual system, and even under adaptation. This is achieved if the input sequence is computed in such a way that the uncertainty on the parameters of the system to be controlled becomes sufficiently small. Then, in the second phase, effort is shifted to control via a traditional certainty equivalence type of strategy. Copyright © 2004 John Wiley & Sons, Ltd.
Activities of granulocyte‐macrophage colony‐stimulating factor and interleukin‐3 on monocytes
Authors: Suzuki Hirohito , Katayama Naoyuki , Ikuta Yasushi , Mukai Katsumi , Fujieda Atsushi , Mitani Hidetsugu , Araki Hiroto , Miyashita Hiroyuki , Hoshino Natsuki , Nishikawa Hiroyoshi , Nishii Kazuhiro , Minami Nobuyuki , Shiku Hiroshi
Published: March 2004

We examined the actions of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and interleukin‐3 (IL‐3) on human monocytes, using a serum‐free culture system. GM‐CSF and IL‐3 did not promote the differentiation of monocytes into macrophages but rather into cells with a phenotype compatible with that of immature dendritic cells (DCs). The addition of fetal bovine serum to serum‐free cultures with GM‐CSF or IL‐3 restored the differentiation of monocytes into macrophages. Cells generated with GM‐CSF or IL‐3 elicited phagocytic activity. Cells generated in the presence of GM‐CSF or IL‐3, followed by the addition of tumor necrosis factor‐α, displayed a phenotype of mature DCs, and primed and stimulated immunogenic peptide‐specific T lymphocytes. Surprisingly, GM‐CSF and IL‐3 inhibited macrophage colony‐stimulating factor (M‐CSF)‐dependent differentiation of monocytes into macrophages and induced differentiation into immature DCs. We asked if the inhibition of M‐CSF‐dependent differentiation into macrophages by GM‐CSF or IL‐3 was associated with the expression of M‐CSF receptors (M‐CSFR). GM‐CSF or IL‐3 down‐regulated the expression of M‐CSFR. These data demonstrate that GM‐CSF and IL‐3 primarily support the differentiation of monocytes into DCs and inhibit M‐CSF‐dependent differentiation into macrophages by suppressing the expression of M‐CSFR, thereby promoting differentiation into DCs. Am. J. Hematol. 75:179–189, 2004. © 2004 Wiley‐Liss, Inc.
Rheological determinants in patients with Gaucher disease and internal inflammation
Authors: Zimran Ari , Bashkin Amir , Elstein Deborah , Rudensky Bernard , Rotstein Rivka , Rozenblat Meirav , Mardi Tamar , Zeltser David , Deutsch Varda , Shapira Itzhak , Berliner Shlomo
Published: March 2004

The purpose of this study was to determine whether the inflammatory response in patients with Gaucher disease (GD) is accompanied by enhanced adhesiveness/aggregation of both red and white blood cells. Sixty patients with GD and matched controls were included. The degree of erythrocyte and leukocyte adhesiveness/aggregation was determined by using a simple slide test and image analysis. Patients with GD had significantly elevated concentrations of fibrinogen (328 vs. 262 mg/dl, P < 0.0001) and accelerated erythrocyte sedimentation rates (27 vs. 13 mm/H, P < 0.005). This was accompanied by a significantly enhanced degree of erythrocyte (75 vs. 85, P < 0.0001) and leukocyte (3.5 vs. 1.3, P < 0.002) adhesiveness/aggregation. The low‐grade, smoldering, and subclinical internal inflammation in individuals with GD is accompanied by an increased degree of erythrocyte and leukocyte adhesiveness/aggregation. These findings might have rheological consequences in terms of microcirculatory slow flow and tissue hypoxemia. Am. J. Hematol. 75:190–194, 2004. © 2004 Wiley‐Liss, Inc.
Accurate and rapid prenatal diagnosis of the most frequent East Mediterranean β‐thalassemia mutations
Authors: Naja R.P. , Kaspar H. , Shbaklo H. , Chakar N. , Makhoul N.J. , Zalloua P.A.
Published: March 2004

β‐Thalassemia is the most common genetic disorder in the Lebanese population. Of the 200 different mutations in the β‐globin gene that leads to thalassemia, the IVSI‐110 (29.87%), IVSI‐6 (20.74%), IVSI‐1 (14.07%), IVSII‐1 (9.13%), Cd29 (9.13%), and Cd30 (3.95%) mutations are the most frequent among Lebanese thalassemic patients. These mutations are also present at high frequencies in the East Mediterranean region. Due to this high prevalence of certain β‐thalassemia mutations, a rapid technique for the prenatal diagnosis of these mutations was implemented. The technique used is based on Real‐Time PCR quantification and melting curve analysis of the amplified fragment using the LightCycler. The DNA samples used for amplification were obtained from CVS or amniotic fluid. Six mutations were easily and efficiently detected using only 3 sets of probes. With this method, mutant genotypes can be easily distinguished from normal alleles. In prenatal diagnosis, the accuracy and the speed of testing are paramount. The method of prenatal β‐thalassemia mutations detection described here is efficient and fast, with the entire procedure including DNA preparation taking less than half a workday. It is safe, does not involve radioactivity, and is accurate showing 100% concordance with conventional DNA sequencing methods. Am. J. Hematol. 75:220–224, 2004. © 2004 Wiley‐Liss, Inc.
Erythrocytosis due to bisphosphoglycerate mutase deficiency with concurrent glucose‐6‐phosphate dehydrogenase (G‐6‐PD) deficiency
Authors: Hoyer James D. , Allen Steven L. , Beutler Ernest , Kubik Kathleen , West Carol , Fairbanks Virgil F.
Published: March 2004

A 28‐year‐old asymptomatic male of Iranian Jewish (Meshadi) heritage was found on routine exam to have an erythrocytosis (RBC = 6.22 × 1012/l, Hgb = 19.2 g/dl, Hct = 58.9%). Splenomegaly was absent on physical exam. There was no family history of erythrocytosis. His oxygen dissociation curve was left‐shifted with a p50 of 19 mmHg (normal = 25–32 mmHg). Hemoglobin electrophoresis showed no abnormalities. DNA sequencing of the hemoglobin β globin gene and both α globin genes did not reveal a mutation. A 2,3‐bisphosphoglycerate (BPG) level was markedly decreased at 0.3 μmol/g Hb (normal = 11.4–19.4 μmol/g Hb). The patient's bisphosphoglycerate mutase (BPGM) enzyme activity was also markedly decreased at 0.16 IU/g Hb (normal = 4.13–5.43 IU/g Hb). A red cell enzyme panel revealed a markedly decreased G‐6‐PD level (0.3 U/g Hb, normal = 8.6–18.6 U/g Hb). His parents and a brother were also available for evaluation. Both parents showed normal 2,3‐BPG levels but BPGM activity approximately 50% of normal. Paradoxically, the brother showed normal BPGM activity but a slightly decreased 2,3‐BPG level. All family members had markedly decreased G‐6‐PD activity. DNA sequencing of the BPGM gene showed the propositus to be homozygous for 185 G→A, Arg 62 Gln in exon 2. Thus, the erythrocytosis in this patient is secondary to low 2,3‐BPG levels, due to a deficiency in BPG mutase. This appears due to consanguinity within this family. Am. J. Hematol. 75:205–208, 2004. © 2004 Wiley‐Liss, Inc.
Cutaneous B‐cell lymphoma: Pathological spectrum and clinical outcome in 51 consecutive patients
Authors: Sah A. , Barrans S.L. , Parapia L.A. , Jack A.S. , Owen R.G.
Published: March 2004

The clinical behavior and optimal treatment of patients presenting with skin infiltration by B‐cell lymphoma have not been established. To clarify this we assessed the clinical and laboratory features of 51 patients presenting with cutaneous infiltration by B‐cell lymphoma. Follow‐up data was available for 46 patients with a median age of 68 years (range 16–89 years) and a median follow‐up of 32.5 months (range 5–123 months). Thirty‐three of 51 (65%) patients had diffuse large B‐cell lymphoma (DLBCL), and 15/51 (29%) had marginal zone lymphoma (MZL). The remaining 3 patients had follicular lymphoma, CLL, and post‐transplant lymphoproliferative disease. Of the 33 patients with DLBCL, follow‐up was available in 29; 24/29 (83%) had primary cutaneous disease, which was unifocal in 17/24 (71%). Following treatment, 8/24 (33%) of the primary cases relapsed. Of the 8 who relapsed, 7 had received local forms of treatment only. Follow‐up data was available in 14/15 patients with MZL. 11/14 (79%) had primary cutaneous disease, which was unifocal in 8 (73%). Following treatment, 4 of these cases relapsed (36%); all had received local therapy only. It is evident from this study that a significant proportion (∽20%) of patients who present with cutaneous infiltration by B‐cell lymphoma have systemic disease. Staging is therefore mandatory in these patients. Approximately 1/3 patients with primary cutaneous DLBCL or MZL ultimately relapse, and relapse rates appear higher in thosepatients receiving local therapy only. Systemic or combined modality therapy may therefore be the most appropriate treatment at presentation. This should be assessed prospectively in randomized trials. Am. J. Hematol. 75:195–199, 2004. © 2004 Wiley‐Liss, Inc.
Blastic mantle cell lymphoma developing concurrently in a patient with chronic myelogenous leukemia and a review of the literature
Authors: Rodler Eve , Welborn Jeanna , Hatcher Sandra , Unger Katherine , Larkin Edward , Gumerlock Paul H. , Wun Theodore , Richman Carol
Published: March 2004

Non‐Hodgkin's lymphoma (NHL) occurring as a synchronous malignancy with chronic myelogenous leukemia (CML) is rare. To our knowledge, this is the first case reported of a patient who developed mantle cell lymphoma (MCL) after therapy with imatinib mesylate for CML. After a 3‐year history of CML, the patient developed a lymphocytosis associated with diarrhea, anorexia, and weight loss. Imaging studies revealed abdominal adenopathy and extensive lymphomatous infiltration of the liver, stomach, pancreas, and kidneys. Flow cytometric and cytogenetic studies were consistent with MCL. Fluorescence in situ hybridization (FISH) of the bone marrow revealed a genetically distinct lymphoid neoplasm rather than an extramedullary blast crisis of CML. The development of lung cancer, prostate cancer, CML and MCL in this patient suggests a genetic predisposition, although other factors, including environmental exposures and therapy with imatinib mesylate could have had a contributory or synergistic role in the development of MCL. Am. J. Hematol. 75:231–238, 2004. © 2004 Wiley‐Liss, Inc.
The Mexican schedule to conduct allogeneic stem cell transplantation is related to a low risk of cytomegalovirus reactivation and disease
Authors: Ruiz‐Argüelles Guillermo J. , Rangel J. David Gómez , Ponce‐de‐León Samuel , González‐Déctor Laura , Reyes‐Núñez Virginia , Garcés‐Eisele Javier
Published: March 2004

The prevalence of cytomegalovirus (CMV) reactivation and disease after non‐myeloablative stem cell transplantation is largely unknown. Using fludarabine combined with alemtuzumab or antithymocyte globulin in the conditioning regimen, some authors have found increased prevalences of CMV disease, whereas other authors using different schedules have observed decreased prevalences. In a group of 17 individuals allografted using the Mexican conditioning regimen, which employs fludarabine, cyclophosphamide, and busulfan, we assessed CMV reactivation, morbidity, and mortality. Before transplant, IgG anti‐CMV antibodies were found in 11 patients and in 10 donors; in 8 cases, both donor and patient had IgG anti‐CMV antibodies. In only one case (6%) was CMV mRNA identified 30 days after the allograft during grade IV acute graft‐versus‐host disease. CMV reactivation, disease, and mortality were very low using our non‐myeloablative stem cell transplantation schedule, which has been shown to be useful for allografting with minimal toxicity and reduced costs. Am. J. Hematol. 75:200–204, 2004. © 2004 Wiley‐Liss, Inc.
Favorable early response of secondary chronic myeloid leukemia to imatinib
Authors: Waldman Dalia , Weintraub Michael , Freeman Arnold , Neumann Yoram , Rechavi Gideon , Toren Amos
Published: March 2004

Second malignant neoplasms are gradually becoming a recognized long‐term complication of successful cancer treatment, and they usually respond poorly to conventional therapy and have an unfavorable outcome. Chronic myeloid leukemia (CML) is a clonal panmyelopathy, rarely seen in children with a specific cytogenetic aberration—the Philadelphia chromosome. The translocation generates an aberrant tyrosine kinase, which drives the malignant process in CML and which is also the molecular target for successful treatment of CML with imatinib. It is also exceedingly rare as a secondary malignant neoplasm in both adults and children. We report two cases of secondary CML. The first occurred after successful treatment for nasopharyngeal carcinoma in a child, and the second after treatment for lymphoma in an adolescent. Both patients had an excellent response to treatment with imatinib and attained complete cytogenetic remissions. We conclude that secondary CML may respond favorably to treatment with imatinib. Am. J. Hematol. 75:217–219, 2004. © 2004 Wiley‐Liss, Inc.
Scrotal ulceration during induction therapy of acute promyelocytic leukemia with ATRA
Authors: Pavithran Keechilat , Arjun Rajalakshmi , Aruna Raman , Thomas Mathew
Published: March 2004

all‐trans‐Retinoic acid (ATRA) has been shown to improve survival in patients with acute promyelocytic leukemia (APML). It is a well‐tolerated drug except for the serious side effect of ATRA syndrome. Dryness of the skin, cheilitis, and xerostomia are the common mucocutaneous side effects. Occurrence of scrotal ulceration is very rare. We report a 13‐year‐old boy who had scrotal ulceration caused by ATRA during the induction therapy of APML. Am. J. Hematol. 75:260–261, 2004. © 2004 Wiley‐Liss, Inc.
Identification of mutations in TCOF1: Use of molecular analysis in the pre‐ and postnatal diagnosis of Treacher Collins syndrome
Authors: Dixon Jill , Ellis Ian , Bottani Armand , Temple Karen , Dixon Michael James
Published: March 2004

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of facial development, which results from mutations in TCOF1. TCS comprises conductive hearing loss, hypoplasia of the mandible and maxilla, downward sloping palpebral fissures and cleft palate. Although, there is usually a reasonable degree of bilateral symmetry, a high degree of both inter‐ and intrafamilial variability is characteristic of TCS. The wide variation in the clinical presentation of different patients, together with the fact that more than 60% of cases arise de novo, can complicate the diagnosis of mild cases and genetic counselling. In the current study, we describe how molecular techniques have been used to facilitate pre‐ and postnatal disease diagnoses in 13 TCS families. © 2004 Wiley‐Liss, Inc.
CDKN1C mutation in Wiedemann–Beckwith syndrome patients reduces RNA splicing efficiency and identifies a splicing enhancer
Authors: Lew Jocelyne M. , Fei Yan Ling , Aleck Kirk , Blencowe Benjamin J. , Weksberg Rosanna , Sadowski Paul D.
Published: March 2004

Wiedemann–Beckwith syndrome (WBS) is a human overgrowth disorder that is accompanied by an increased risk of embryonal tumors and is associated with dsyregulation of the imprinting of genes in chromosome 11p15.5. Maternally inherited mutations in the imprinted CDKN1C gene are known to be associated with WBS. We have identified a novel mutation in several members of a large family affected by WBS. The mutation is a G → T change in a run of seven G's near the 5′ splice site of intron 3. All obligate carriers and affected individuals carry the mutation, and in each affected case, the allele was inherited maternally, strongly suggesting a role in causing WBS. The mutation is located in a poly‐G tract in the intron; intronic G‐rich sequences in other genes have been shown to have a role in promoting splicing. In transfected 293HEK cells, we found that the G → T mutation reduced splicing efficiency. Mutation of all seven G's in the poly‐G tract further reduced splicing efficiency, supporting a role for the G‐tract as a splicing enhancer. The fibroblasts of one affected patient showed a similar reduction in splicing efficiency. Maternal monoallelic expression of CDKN1C was verified in this patient cell line. However, the total amount of spliced message was not reduced by the mutation in spite of the reduced efficiency of splicing. We discuss the possible role of the splicing defect in the pathogenesis of WBS in this pedigree. © 2004 Wiley‐Liss, Inc.
Isolated congenital anosmia with morphologically normal olfactory bulb in two Iranian families: A new clinical entity?
Authors: Ghadami Mohsen , Majidzadeh‐A Keyvan , Morovvati Saeid , Damavandi Elia , Nishimura Gen , Komatsu Kazuki , Kinoshita Akira , Najafi Mohammad‐Taghi , Niikawa Norio , Yoshiura Koh‐ichiro
Published: March 2004

Congenital total loss of the sense of smell occurs as a part of a syndrome or isolated anosmia. Kallmann syndrome is the most well known congenital anosmia associated with hypogonadotropic hypogonadism. Isolated congenital anosmia (ICA) is a very rare condition and appears to be due to changes in the olfactory epithelium or to aplasia of the olfactory nerve, bulb, and tract. Here we report two unrelated Iranian families with ICA. One family consisted of nine affected members, and the other family contained three affected members. Clinical history, physical examination, and smell testing by intravenous injection of combined vitamins (Alinamin™, Takeda Pharmaceutical Co. Ltd., Japan) confirmed the disease in each affected member. No signs of hypogonadism or other neurological disorders were observed in any affected members. Family analysis with the complete ascertainment method under assumption of the same condition in the two families suggested that the disease is not inconsistent with an autosomal dominant mode with incomplete penetrance. The inheritance in one family appears unusual, i.e., there were no affected individuals in the third generation. When only two upper generations in the family are concerned, the segregation ratio was 0.39 ± 0.11. Male‐to‐male transmissions were observed and both sexes were affected in both families. Magnetic resonance imaging (MRI) of the olfactory bulb and sulcus revealed no evidence of morphological changes in all affected members, suggesting that these patients have either a defect in the olfactory epithelium or a functional defect in the olfactory cortex. © 2004 Wiley‐Liss, Inc.
Elevated catecholamine metabolites in patients with Costello syndrome
Authors: Gripp Karen W. , Kawame Hiroshi , Viskochil David H. , Nicholson Linda
Published: March 2004

Costello syndrome is a rare congenital anomaly syndrome with a predisposition to specific tumors, including neuroblastoma, rhabdomyosarcoma, and transitional cell carcinoma of the bladder. The increased risk for solid tumors led to the proposal of a tumor screening protocol. A screening test for neuroblastoma consists of measuring catecholamine metabolites in urine, an assay that may also be used for diagnostic confirmation of a suspected catecholamine secreting tumor. We report eight patients with Costello syndrome with elevated catecholamine metabolites, vanillylmandelic acid (VMA) and/or homovanillic acid (HVA), in urine. Each patient had additional laboratory and/or imaging studies. None of the patients was found to have a neuroblastoma or another catecholamine secreting tumor. In two cases, the assays were performed because the patients were symptomatic with diaphoresis and hypertension, respectively, and in the other six cases the assays were performed in order to screen for neuroblastoma. The pathophysiology for the catecholamine metabolite abnormality in these patients with Costello syndrome remains unclear. However, it appears that in this patient group an elevation above the normal limit, defined as 2 standard deviations (SD) above the mean for age, is more likely to be a variant, rather than a sign of a neuroblastoma. Thus, it may be prudent not to use this assay as a screening test, and to take the frequently elevated results into consideration when interpreting diagnostic assays. © 2004 Wiley‐Liss, Inc.
Association between cytochrome P450 2D6 genotype and harm avoidance
Authors: Roberts Rebecca L. , Luty Suzanne E. , Mulder Roger T. , Joyce Peter R. , Kennedy Martin A.
Published: March 2004

Genetic polymorphisms within the serotonergic and dopaminergic neurotransmitter systems may be associated with heightened harm avoidance and novelty seeking. It is also conceivable that polymorphisms in enzymes that mediate the metabolism of endogenous amines within the brain may influence these components of temperament. The CYP2D6 enzyme is expressed at low levels in the brain, and has been shown to mediate the formation of the neurotransmitters serotonin and dopamine from trace amines. Some 5–10% of Caucasians are CYP2D6 deficient due to inactivating mutations in the CYP2D6 gene, and are termed poor metabolizers (PMs). In this study, we investigated whether temperament varied significantly between PMs and CYP2D6 extensive metabolizers (EMs) using the Temperament and Character Inventory (TCI). CYP2D6 genotypes were determined for 121 depressed patients. Of these patients, 113 were inferred from genotype as being EMs and eight as PMs. A significant difference in temperament was observed between inferred CYP2D6 EM and PM individuals. CYP2D6 PMs had significantly lower harm avoidance scores (P = 0.003) than EMs. Furthermore, analysis of the harm avoidance sub‐scales revealed that the CYP2D6 PMs scored significantly lower on “fear of uncertainty” (P < 0.001), fatigability (P = 0.009), and shyness (P = 0.038) than EMs, but did not differ significantly from EMs on the worry/pessimism sub‐scale. No significant difference in character scores was detected between inferred CYP2D6 EMs and PMs. Our findings suggest that the CYP2D6 polymorphism may impact on personality, and one potential mechanism for this would be by influencing the generation of endogenous neurotransmitters in the brain. © 2004 Wiley‐Liss, Inc.
Expression of CCR7 in multiple sclerosis: Implications for CNS immunity
Authors: Kivisäkk Pia , Mahad Don J. , Callahan Melissa K. , Sikora Keith , Trebst Corinna , Tucky Barbara , Wujek Jerome , Ravid Rivka , Staugaitis Susan M. , Lassmann Hans , Ransohoff Richard M.
Published: March 2004

It is unclear how immune cells traffic between the lymphoid compartment and the central nervous system (CNS), which lacks lymphatic vessels and is shielded by the blood–brain barrier. We studied the expression of CCR7, a chemokine receptor required for migration of T cells and dendritic cells (DCs) to lymphoid organs, in the CNS of patients with multiple sclerosis (MS) to gain insight into pathways for CNS immune cell trafficking. Inflamed MS lesions contained numerous CCR7+ myeloid cells expressing major histocompatibility complex class II, CD68 and CD86, consistent with maturing DCs. CCR7+ DCs also were identified in cerebrospinal fluid (CSF). These observations suggested that the afferent limb of CNS immunity is comprised, in part, of DCs, which are generated within the CNS and migrate to deep cervical lymph nodes through the CSF after antigen capture. Ninety percent of CSF T cells expressed CCR7 and CSF from patients with MS was relatively depleted of CCR7‐negative effector‐memory T cells. In contrast, all T cells in parenchymal MS lesions lacked CCR7, indicating local retention and differentiation of central‐memory T cells upon restimulation by antigen within the CNS. These data suggested that the efferent limb of CNS immunity is executed by central‐memory T cells, which enter CSF directly from the circulation. Ann Neurol 2004
The urokinase receptor is overexpressed in the AIDs dementia complex and other neurological manifestations
Authors: Cinque Paola , Nebuloni Manuela , Santovito Maria Lisa , Price Richard W. , Gisslen Magnus , Hagberg Lars , Bestetti Arabella , Vago Gianluca , Lazzarin Adriano , Blasi Francesco , Sidenius Nicolai
Published: March 2004

The urokinase‐type plasminogen activator (uPA) and its receptor (uPAR) play an important role in extracellular matrix degradation and cell migration in the central nervous system (CNS). To investigate the role of the uPA/uPAR system in the pathophysiology of acquired immunodeficiency syndrome dementia complex (ADC), we measured soluble uPAR (suPAR) levels in cerebrospinal fluid (CSF) and plasma from human immunodeficiency virus (HIV)‐1–infected patients and controls. CSF suPAR levels were significantly higher in HIV‐1–infected patients than in controls and in patients with ADC or opportunistic CNS infections (CNS‐OIs) than in neurologically asymptomatic patients, irrespective of HIV‐1 disease stage. The highest levels of suPAR were found in patients with ADC, and among those with CNS‐OIs in patients with cytomegalovirus encephalitis or cryptococcosis. Plasma suPAR levels were higher in HIV‐1–infected patients than in controls and increased with HIV‐1 disease stage regardless of the presence of CNS disease. In patients with ADC or CNS‐OIs, CSF suPAR levels correlated with CSF HIV‐1 RNA, but not with plasma suPAR concentrations. Highly active antiretroviral therapy was associated with a significant and parallel decrease of both CSF suPAR and HIV‐1 RNA. In brain tissue from patients with HIV‐1 encephalitis, uPAR was highly expressed by microglial and multinucleated giant cells staining positively for HIV‐1. The overexpression of uPAR in the CNS of patients with ADC suggests that the uPA/uPAR system may contribute to the tissue injury and neuronal damage in this disease. Ann Neurol 2004
Desmin‐related myopathy with mallory body–like inclusions is caused by mutations of the selenoprotein N gene
Authors: Ferreiro Ana , Ceuterick‐de Groote Chantal , Marks Jared J. , Goemans Nathalie , Schreiber Gudrun , Hanefeld Folker , Fardeau Michel , Martin Jean‐Jacques , Goebel Hans H. , Richard Pascale , Guicheney Pascale , Bönnemann Carsten G.
Published: March 2004

Desmin‐related myopathies (DRMs) are a heterogeneous group of muscle disorders, morphologically defined by intrasarcoplasmic aggregates of desmin. Mutations in the desmin and the α‐B crystallin genes account for approximately one third of the DRM cases. The genetic basis of the other forms remain unknown, including the early‐onset, recessive form with Mallory body–like inclusions (MB‐DRMs), first described in five related German patients. Recently, we identified the selenoprotein N gene (SEPN1) as responsible for SEPN‐related myopathy (SEPN‐RM), a unique early‐onset myopathy formerly divided in two different nosological categories: rigid spine muscular dystrophy and the severe form of classical multiminicore disease. The finding of Mallory body–like inclusions in two cases of genetically documented SEPN‐RM led us to suspect a relationship between MB‐DRM and SEPN1. In the original MB‐DRM German family, we demonstrated a linkage of the disease to the SEPN1 locus (1p36), and subsequently a homozygous SEPN1 deletion (del 92 nucleotide −19/+73) in the affected patients. A comparative reevaluation showed that MB‐DRM and SEPN‐RM share identical clinical features. Therefore, we propose that MB‐DRM should be categorized as SEPN‐RM. These findings substantiate the molecular heterogeneity of DRM, expand the morphological spectrum of SEPN‐RM, and implicate a necessary reassessment of the nosological boundaries in early‐onset myopathies. Ann Neurol 2004
Agostic Interactions in d0Metal Alkyl Complexes
Authors: Scherer Wolfgang , McGrady G. Sean
Published: March 2004

The phenomenon of agostic interactions is reviewed and the nature of the interaction is revisited. A historical perspective is followed by an overview of experimental techniques used to diagnose agostic behavior, and previous interpretations of agostic bonding are presented. A series of simple metal alkyl complexes is considered and a new model for the phenomenon in d0systems is developed which sets them apart from agostic late‐transition‐metal complexes. Factors such as the valence electron count and coordination number of the metal center are revealed to be unimportant in facilitating the interaction in most d0systems. The charge density distribution in several transition‐metal alkyl complexes is explored by experimental and theoretical techniques, including the powerful “Atoms in Molecules” approach. Local charge concentrations are shown to play an important role in the agostic interaction. Finally, we demonstrate for the first time a way to manipulate and control the magnitude and disposition of such local charge concentrations, and hence the strength of agostic interactions in d0metal alkyl complexes.
The Chemical Laboratory: Source of Progress or Chamber of Horrors?
Authors: Krätz Otto
Published: March 2004

Must chemistry stink and go bang?The laboratory as a forbidding setting, as a workshop of extraordinary obscurantists whose sole unholy purpose is to produce all manner of poisons and acids, is a fond stereotype in literary fiction. Realistic descriptions are reserved exclusively for chemist writers. A foray through the literature shows that chemistry sometimes has a sinister public image.
Old Clusters with New Tricks: Engineering S⋅⋅⋅S Interactions and Novel Physical Properties in Sulfite‐Based Dawson Clusters
Authors: Long De‐Liang , Kögerler Paul , Cronin Leroy
Published: March 2004

Unprecedented 18‐molybdosulfite Dawson clusters encapsulate two pyramidal sulfite ions as templates, and exhibit a short S⋅⋅⋅S interaction between the two ions, which was characterized by DFT calculations. The [Mo18O54(SO3)2]4− ion is the first discrete thermochromic polyoxometalate cluster: its color varies from pale yellow at 77 K to deep red at 500 K (see picture).
Crystallographic report: (2,2′‐Bipyridine)bis(N,N‐dibenzyldithiocarbamato)zinc(II)
Authors: Lai Chian Sing , Tiekink Edward R. T.
Published: March 2004

The structure of Zn[S2CN(CH2Ph)2]2(2,2′‐bipy) features a distorted trigonal prismatic geometry around the zinc centre defined by an N2S4 donor set; the molecule has two‐fold symmetry. Copyright © 2004 John Wiley & Sons, Ltd.
Crystallographic report: Bis(2‐diphenylglycolato‐O)bis(1,10‐phenanthroline‐N,N′)zinc(II), [Zn(C14H11O3)2(C12H8N2)2]
Authors: Carballo Rosa , Covelo Berta , García‐Martinez Emilia , Vázquez‐López Ezequiel M. , Castiñeiras Alfonso
Published: March 2004

The structure of [Zn(HB)2(1,10‐phen)2] (HB = diphenylglycolato) comprises mononuclear molecules with the zinc(II) cation situated on a two fold axis and octahedrally coordinated by an N4O2 donor set. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis and neurotropic activity of silyl propargyl alcohols and sulfides
Authors: Abele Ramona , Zvejniece Liga , Abele Edgars , Rubina Kira , Arsenyan Pavel , Vandish Marina , Pudova Olga , Dambrova Maija , Domracheva Ilona , Shestakova Irina , Popelis Juris , Lukevics Edmunds
Published: March 2004

New silicon derivatives of hetaryl propargyl sulfides and propargyl alcohols were synthesized using phase‐transfer catalytic and organometallic methods. These compounds were tested for acute toxicity and neurotropic activity in the pentylenetetrazole test, and for phenamine hypothermia, phenamine hyperactivity and passive avoidance response tests. We have found that the silyl propargyl alcohols and sulfides are low toxicity compounds, the LD50 being 700–1300 mg kg−1. In the PAR test, the synthesized compounds exerted some memory‐improving activity. For di‐1‐(3‐methyl‐3‐hydroxybutyn‐1‐yl)methyl(3‐iodopropyl)silane (16) the effect was statistically significant and amounted to 250% of the control level. In the pentylenetetrazole test, all compounds possessed anticonvulsant activity, the most active compounds being 3‐(benzoxazolylthio)‐1‐propynyl(trimethyl)silane (6) and di‐[2‐(1‐hydroxycyclohexyl)ethynyl]methyl(3‐iodopropyl)silane (17). The phenamine‐induced hyperactivity was significantly elevated after treatment with (3‐trimethylsilyl‐2‐propynyl)thiobenzene (1) or di‐[1‐(3‐methyl‐3‐hydroxybutyn‐1‐yl)diphenylsilane (12). Our data show that these silicon derivatives of hetaryl propargyl sulfides and propargyl alcohols possess certain memory improving and anticonvulsant activity that should be studied in detail to evaluate the receptor systems involved. Copyright © 2004 John Wiley & Sons, Ltd.
Review: Synthetic methodologies in siloxanes
Authors: Purkayastha Arup , Baruah Jubaraj Bikash
Published: March 2004

This review describes the various types and synthetic strategies for the production of siloxanes. A description is given of the various synthetic methods for the production of organic compounds with silicon–oxygen bonds. The different types of siloxane are described, with the emphasis being on their structural aspects. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis, characterization and cytotoxicity of some triarylbismuth(V) di(N‐p‐toluenesulfonyl) aminoacetates and the crystal structure of (4‐CH3C6H4SO2NHCH2CO2)2Bi(C6H4Cl‐4)3
Authors: Yu Lin , Ma Yong‐Qiang , Wang Guo‐Cang , Song Hai‐Bin , Wang Hong‐Geng , Li Jin‐Shan , Cui Jing‐Rong , Wang Rui‐Qing
Published: March 2004

A series of triarylbismuth(V) di(N‐p‐toluenesulfonyl)aminoacetates with the formula (4‐CH3C6H4SO2NHCH2CO2)2BiAr3 (ArC6H5, 4‐CH3C6H4, 4‐ClC6H4, 4‐BrC6H4) were synthesized and characterized by elemental analysis, IR, 1H NMR and mass spectra. The crystal structure of (4‐CH3C6H4SO2NHCH2CO2)2Bi(C6H4Cl‐4)3 was determined and shows the bismuth to exist in a distorted trigonal bipyramidal geometry. Four human neoplastic cell lines (HL‐60, PC‐3MIE8, BGC‐823 and MDA‐MB‐435) were used to screen these compounds. The results indicate that these compounds at 10 μM show cytotoxicity. Copyright © 2004 John Wiley & Sons, Ltd.
Natural rubber–isotactic polypropylene thermoplastic blends
Authors: Varghese Siby , Alex Rosamma , Kuriakose Baby
Published: March 2004

Thermoplastic elastomers, prepared by melt blending of natural rubber (NR) and isotactic polypropylene (PP) through a dynamic vulcanization technique, were developed during the later 1970s. However, they have certain drawbacks due to thermal degradation and higher molecular weight of NR. In the study reported here, NR was masticated to different levels prior its addition to isotactic polypropylene to improve the flow properties and to reduce the incompatibility resulting from molecular weight mismatch of NR/PP thermoplastic blends. Mixing energy curves of uncrosslinked blends and those of dynamically vulcanized blends crosslinked using different cure systems were compared. The mixing energy curves of blends containing NR of different molecular weight (Mn) and two grades of PP (injection and film grades) were also compared. Technological and processing properties of the dynamically vulcanized (sulphur and peroxide cure systems) and unvulcanized blends were compared with those of the samples containing unmasticated NR. The results indicated that a number average molecular weight in the range 4 × 105 for NR increased the procoessability without significantly affecting the technological properties of NR/PP thermoplastic blends. Among the three cure systems studied Luperox 101 and dicumyl peroxide gave better technological properties than the sulphur‐cured samples. Two antioxidants, viz. quinoline (TDQ) and imidazole (MBI) type, were tried in NR/PP blends. It was found that TDQ imparts better aging resistance compared to MBI. The improvement in processability due to the reduction in molecular weight of natural rubber by mastication is more noticeable in the case of peroxide vulcanized blends compared to sulphur vulcanized samples. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2063–2068, 2004
Hydrophobic properties of ethylene–vinyl alcohol copolymer treated with plasma source ion implantation
Authors: Kim Kibeom , Sung Woonmo , Park Hyunjin , Lee Yeonhee , Han Seunghee , Kim Wangjune
Published: March 2004

The industrial use of ethylene–vinyl alcohol copolymer (EVOH) film is limited because it is easily degraded by moisture. The plasma source ion implantation (PSII) technique with CF4 or CH4 gas was used for the EVOH film to improve the surface hydrophobic properties. Variables examined in implantation were ion energy (0–10 keV), treatment time (5 s–5 min), and ion species. The hydrophobic properties of EVOH films were greatly enhanced after a CF4 PSII treatment, as evidenced by an increased contact angle from 66° to above 100° at ‐5 keV, and remained relatively unchanged during the period of 28 days. X‐ray photoelectron spectroscopy, atomic force microscopy, and O2 permeability were used to characterize the surface properties of EVOH films treated with PSII. The improved hydrophobic properties were closely related to the formation of fluorine‐containing functional groups such as CF, CF2, and CF3 on the modified surface. The percentage distribution of carbon functional groups supports the role of CF2 and CF3 groups in surface modification. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2069–2075, 2004
Ion‐conducting polymer gels of polyacrylamide embedded with K2CO3
Authors: Song Wensheng , Wang Yuxin , Deng Huining
Published: March 2004

A highly ionic conductive solid‐gel membrane based on polyacrylamide hydrogels with a K2CO3 additive was investigated. The polymer‐based gel was prepared by adding ionic species K2CO3 to a monomer solution followed by polymerization. After polymerization, the ionic species was embedded in the polymer‐based gel, where it remained. The ionic species behaved like a liquid electrolyte, whereas the polymer‐based solid‐gel membrane provided a smooth impenetrable surface that allowed for the exchange of ions. The gel membranes were obtained in the form of thin films of reasonable mechanical strength. Their ambient temperature conductivities were in the range 10−2 to 10−1 S/cm. The effect of K2CO3 concentration on the conductivity of the gels prepared was examined in the temperature range from 0 to 100°C. The microstructure and chemical composition of the gels studied were characterized by environmental scanning electron microscopy and FTIR, respectively. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2076–2081, 2004
A phosphorus‐containing diamine for flame‐retardant, high‐functionality epoxy resins. I. Synthesis, reactivity, and thermal degradation properties
Authors: Liu Weichang , Varley Russell J. , Simon George P.
Published: March 2004

A phosphorus‐containing amine, bis(4‐aminophenoxy)phenyl phosphine oxide (BAPP), suitable for curing epoxy resins with improved fire performance was synthesized and characterized with Fourier transform infrared spectroscopy and nuclear magnetic resonance. The reactivity of the amino group was evaluated by differential scanning calorimetry of the epoxy–amine mixture and by proton nuclear magnetic resonance of the amino unit. With BAPP as a curing agent, a range of high‐functionality, aerospace epoxy resins were cured, and the dynamic kinetic parameters calculated from Kissinger's and Ozawa's models were compared with those from the more widely used amines. The thermal degradation properties of the phosphorus‐containing epoxy resins were studied by thermogravimetric analysis, the degradation activation energy was calculated, and a multistep thermal degradation process was observed. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2093–2100, 2004
Nanocomposites of poly(methyl methacrylate) and organically modified layered silicates by melt intercalation
Authors: Shen Zhiqi , Simon George P. , Cheng Yi‐Bing
Published: March 2004

Polymer‐layered silicate nanocomposites of poly(methyl methacrylate) (PMMA) and an organically modified silicate [tetraallkyl ditallow ammonium bentonite (B34)] system prepared via melt intercalation were studied. The saturation ratio of PMMA to B34 was 25:75 (w/w), as determined by dynamic mechanical thermal analysis, differential scanning calorimetry, and X‐ray diffraction. The interaction between PMMA and B34 was detected by Fourier transform infrared spectrometry, which showed two new absorption bands of PMMA/B34 hybrids in comparison with unannealed physical mixtures of PMMA and B34. The degradation temperature of the PMMA/B34 hybrids was 26°C higher than that of neat PMMA according to thermogravimetric analysis, the thermal stability of the hybrids having been enhanced. The glass‐transition temperature of excess PMMA remaining outside the clay galleries was about 12–19°C higher than that of neat PMMA. A structural model of the hybrid was also presented. It involves some PMMA chains diffusing into the gallery of B34 and expanding it by 6.8 Å and some penetrating and interacting with the organic chains of the modified cations. Some of the PMMA chains partly contained inside the clay layers were entangled with those remaining outside when PMMA in excess of the saturation ratio was used. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2101–2115, 2004
Concanavalin A attached poly(p‐chloromethylstyrene) beads for glycoenzyme separation
Authors: Bahar T. , Tuncel A.
Published: March 2004

Crosslinked poly(p‐chloromethylstyrene) (PCMS) beads were produced by suspension polymerization. The beads had a nonporous but reasonably rough surface structure. Because of this property, a relatively high external surface area (i.e., 14.1 m2/g) was obtained with the proposed carrier. A biospecific ligand commonly used in the affinity chromatography of various glycoenzymes, concanavalin A (Con A), was covalently attached onto the bead surface by a direct chemical reaction. PCMS/Con A beads were then used for the separation of a model glycoenzyme, invertase, from its crude solution. The appropriate invertase adsorption and desorption conditions of the affinity system were investigated. The desorption of invertase from the carrier was achieved by the use of methyl‐α‐D‐mannopyranoside (MMP) as the counterligand. The effects of the MMP and salt concentrations and the temperature on the desorption behavior of invertase were investigated. The MMP concentration and temperature were found to be the dominant parameters controlling the desorption. Iterative experiments involving five reversible adsorption–desorption cycles were performed with the same particles to monitor the changes that occurred in the invertase adsorption–desorption capacities of Con A immobilized beads. The reversible adsorption–desorption stability was significantly improved by the crosslinking of Con A immobilized on the beads. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2116–2124, 2004
Preparation and thermal analysis of cotton–clay nanocomposites
Authors: White Leslie A.
Published: March 2004

Nanocomposites were produced from cotton with montmorillonite clay used as the nanofiller material. Three exfoliation and intercalation methods with different solvents and clay pretreatment techniques were tested for the production of these organic–inorganic hybrids. The method that resulted in superior clay–cotton nanocomposites used a clay pretreatment with 4‐methylmorpholine‐N‐oxide as the cotton solvent. The nanocomposites showed significant improvements in the thermal properties in comparison with unbleached cotton and cotton processed under the conditions for nanocomposite preparation. The degradation temperature of the nanocomposites increased by 45°C, and the char yields for some compositions were twice those of unbleached cotton. The crystalline melt of the materials decreased by 15°C. Future research will include the development of textiles based on these cotton–clay materials and testing for flame‐retardant properties and product strength. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2125–2131, 2004