bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model of the acid sphingomyelinase phosphoesterase domain based on its remote structural homolog purple acid phosphatase
Authors: Seto Marian , Whitlow Marc , McCarrick Margaret A. , Srinivasan Subha , Zhu Ying , Pagila Rene , Mintzer Robert , Light David , Johns Anthony , Meurer‐Ogden Janet A. 
Published: November 2004

AbstractSequence profile and fold recognition methods identified mammalian purple acid phosphatase (PAP), a member of a dimetal‐containing phosphoesterase (DMP) family, as a remote homolog of human acid sphingomyelinase (ASM). A model of the phosphoesterase domain of ASM was built based on its predicted secondary structure and the metal‐coordinating residues of PAP. Due to the low sequence identity between ASM and PAP (∼15%), the highest degree of confidence in the model resides in the metal‐binding motifs. The ASM model predicts residues Asp 206, Asp 278, Asn 318, His 425, and His 457 to be dimetal coordinating. A putative orientation for the phosphorylcholine head group of the ASM substrate, sphingomyelin (SM), was made based on the predicted catalysis of the phosphorus–oxygen bond in the active site of ASM and on a structural comparison of the PAP–phosphate complex to the C‐reactive protein–phosphorylcholine complex. These complexes revealed similar spatial interactions between the metal‐coordinating residues, the metals, and the phosphate groups, suggesting a putative orientation for the head group in ASM consistent with the mechanism considerations. A conserved sequence motif in ASM, NX3CX3N, was identified (Asn 381 to Asn 389) and is predicted to interact with the choline amine moiety in SM. The resulting ASM model suggests that the enzyme uses an SN2‐type catalytic mechanism to hydrolyze SM, similar to other DMPs. His 319 in ASM is predicted to protonate the ceramide‐leaving group in the catalysis of SM. The putative functional roles of several ASM Niemann‐Pick missense mutations, located in the predicted phosphoesterase domain, are discussed in context to the model.
High‐dose melphalan with autologous stem cell transplantation after VAD induction chemotherapy for treatment of amyloid light chain amyloidosis: a single centre prospective phase II study
Authors: Perz Jolanta B. , Schonland Stefan O. , Hundemer Michael , Kristen Arnt V. , Dengler Thomas J. , Zeier Martin , Linke Reinhold P. , Ho Anthony D. , Goldschmidt Hartmut 
Published: November 2004

SummaryAmyloid light chain (AL) amyloidosis is the result of a clonal plasma cell expansion, in which monoclonal light chains transform to amyloid deposit in various tissues and can lead to organ dysfunction and organ failure. The median survival of patients with AL amyloidosis without therapy is 10–14 months. With high‐dose melphalan (HDM) and autologous stem cell transplantation (ASCT), haematological and clinical remission rates of up to 50% of treated patients have been reported from phase II studies. HDM followed by ASCT appears to prolong survival in patients, if haematological remission can be reached. In this phase II study, we evaluated vincristine, adriamycin and dexamethasone (VAD) as induction chemotherapy prior to stem cell mobilization and HDM with ASCT. The regimen was, in general, feasible in patients with AL amyloidosis, but VAD chemotherapy had a considerable World Health Organization (WHO) grade III–IV toxicity (25%) and mortality (7%) rate. VAD pretreatment did not interfere with stem cell mobilization and HDM with ASCT was possible in 86% of patients. The overall treatment efficacy was comparable with reported results of HDM and ASCT without preceding chemotherapy. We could not show an additional benefit of VAD induction in terms of increasing haematological response rate; however the 13% mortality rate after HDM and ASCT in our series was lower than the previous report.
Platelet count, previous infection and FCGR2B genotype predict development of chronic disease in newly diagnosed idiopathic thrombocytopenia in childhood: results of a prospective study
Authors: Bruin Marrie , Bierings Marc , Uiterwaal Cuno , Révész Tom , Bode Lonneke , Wiesman Marie‐Elize , Kuijpers Taco , Tamminga Rienk , de Haas Masja 
Published: November 2004

SummaryAbout 25–30% of children with acute idiopathic thrombocytopenia (ITP) develop chronic disease. It is not well known which patient characteristics influence the course of the ITP. A prospective study in 60 children with newly diagnosed ITP was performed. The aim of the study was to identify patient characteristics at the onset of thrombocytopenia that predicts the progression to chronic ITP. Clinical data and blood samples were collected at several time points during the first 6 months of the disease. Variables predicting chronic disease, as calculated in a multivariate logistic regression analysis, were a platelet count >10 × 109/l at the onset [odds ratio (OR) 1·1, 95% confidence interval (CI) 1·01–1·14], the absence of infection shortly before the onset of the disease (OR 4·8, CI 1·16–19·57) and FGR2B‐232I/T genotype (OR 7·9, CI 0·96–65·27). The latter may point at an immune‐modulating role of FcγRIIb in ITP. Although only three patients had serious bleeds, 35 patients received immune‐modulating treatment for low platelet counts only. Seventeen patients were treated with intravenous immunoglobulin (IVIG) and 18 patients received corticosteroids. Patient variables did not differ between these treatment groups. However, patients receiving IVIG had significantly lower risk for chronic disease.
The P303T mutation in the human factor VII (FVII) gene alters the conformational state of the enzyme and causes a severe functional deficiency
Authors: Peyvandi Flora , Cristofaro Raimondo De , Garagiola Isabella , Palla Roberta , Akhavan Sepideh , Landolfi Raffaele , Mannucci Pier Mannuccio 
Published: November 2004

SummaryWe report the results of in vitro expression and biochemical characterization of the naturally occurring type II mutation Pro303Thr (P303T) in the factor VII (FVII) gene. Recombinant activated mutated FVII (FVIIa303T), compared with the activated wild‐type FVII (FVIIaWT), showed reduced amidase activity toward synthetic substrates, especially when the observed reduced binding affinity for human soluble tissue factor (TF) (Kd from 4·4 nmol/l for FVIIaWT to 17·3 nmol/l for FVIIa303T) was overcome by a fully saturating TF concentration. Likewise, factor X (FX) hydrolysis by FVIIa303T showed a reduced activity in the absence (and more severely in the presence) of TF (kcat/Km from 2·3 × 107/mol/l s for FVIIaWT to 8·7 × 105/mol/l s for FVIIa303T). These results showed that the mutant FVIIa is more shifted toward a zymogen‐like form compared to FVIIaWT, suggesting that P303 facilitates the conformational transitions that stabilize the active form of FVIIa. The alteration of these allosteric equilibria is especially evident in the presence of TF, which was unable to shift the equilibrium toward a fully active FVIIa form. Additional experiments showed that both TF‐catalysed FVII303T autoactivation and FVII303T activation by activated FX in the presence of TF were severely impaired, mainly because of an increase of the Km value. Altogether, these defects may explain the severe bleeding symptoms in a patient carrying the FVIIP303T mutation.
The impact of birth weight on coronary heart disease morbidity and mortality in a birth cohort followed up for 85 years: a population‐based study of men born in 1913
Authors: Eriksson M. , Wallander M.‐A. , Krakau I. , Wedel H. , Svärdsudd K. 
Published: November 2004

Abstract.Objectives. To analyse whether there is a relationship between birth weight on the one hand and coronary heart disease (CHD) and cardiovascular disease (CVD) mortality and morbidity on the other, whether such a relationship is influenced by potential modifying factors from the time of birth, adult height and the presence of diabetes, and what significance these possible associations might have for the CHD and CVD rates in the general population.Design. Population‐based birth cohort.Setting. Sweden.Subjects. A total of 1319 singleton men born in 1913, surviving until age 20 and from then on followed until 85 years of age.Main outcome measures. CHD and CVD mortality and morbidity events.Results. The gestational age adjusted CHD and CVD mortality and morbidity hazard ratios were virtually unaffected by birth weight. Taking possible effect‐modifying variables into account did not change the results. The population attributable risk percentage for CHD and CVD mortality and morbidity due to a birth weight ≤3000 g was 1% or less.Conclusions. Birth weight did not significantly affect CHD or CVD mortality or morbidity. A birth weight ≤3000 g contributes little to the burden of CHD and CVD on a community level.
Inhibition of l‐arginine transport in platelets by asymmetric dimethylarginine and NG‐monomethyl‐l‐arginine: Effects of arterial hypertension
Authors: Brunini TMC , Moss MB , Siqueira MAS , Meirelles LR , Rozentul AL , Mann GE , Ellory JC , Soares de Moura R , Mendes‐Ribeiro AC 
Published: November 2004

Summary1. Nitric oxide (NO) produced by human platelets plays an important role in all stages of platelet activation. l‐Arginine, the precursor for NO synthesis, modulates NO production by platelets. The l‐arginine analogues asymmetric dimethylarginine (ADMA) and NG‐monomethyl‐l‐arginine (l‐NMMA) are endogenous inhibitors of nitric oxide synthase (NOS), involved in the physiopathology of arterial hypertension. The aim of the present study was to investigate the inhibitory effects of endogenous and exogenous l‐arginine analogues on l‐arginine influx in platelets from healthy controls and hypertensive patients.2. Twelve patients with uncomplicated essential hypertension (stage I) and 15 age‐matched normotensive controls participated in the present study. Platelets were isolated and incubated with l‐[3H]‐arginine and increasing concentrations of l‐arginine analogues (5–2000 µmol/L).3. The influx of l‐arginine was inhibited in a concentration‐dependent manner by l‐NMMA in platelets from controls (Ki = 42 ± 6 µmol/L) and this inhibitory effect was markedly higher in hypertensive platelets (Ki = 23 ± 4 µmol/L).4. Similarly, the Ki for ADMA inhibition of l‐arginine transport was significantly more pronounced in platelets from hypertensive patients (Ki = 16 ± 1 µmol/L) compared with controls (Ki = 27 ± 2 µmol/L).5. In contrast, NG‐nitro‐l‐arginine methyl ester (l‐NAME) was found to be a weak inhibitor of l‐arginine influx in platelets from controls (Ki = 1917 ± 319 µmol/L) and hypertensive patients (Ki = 2279 ± 578 µmol/L). Aminoguanidine, a selective inhibitor of inducible NOS, failed to inhibit l‐arginine transport.6. Our findings provide the first evidence that ADMA and l‐NMMA markedly inhibit l‐arginine transport in human platelets, an effect that is more pronounced in hypertensive patients. It is possible that endogenous l‐arginine analogues, by inhibiting NO synthesis, are involved in the platelet activation present in hypertension.
Improvement of spatial cognition with dietary docosahexaenoic acid is associated with an increase in Fos expression in rat CA1 hippocampus
Authors: Tanabe Yoko , Hashimoto Michio , Sugioka Kozo , Maruyama Megumi , Fujii Yoshimi , Hagiwara Rika , Hara Toshiko , Hossain Shahdat Md , Shido Osamu 
Published: November 2004

Summary1. Twenty 5‐week‐old male Wistar rats were divided into two groups: one group was fed a fish oil‐deficient diet and the other group was fed the same diet supplemented with per orally administered docosahexaenoic acid (DHA) for 12 weeks.2. Six weeks after the start of the administration of DHA, rats were trained for 6 weeks to acquire a reward at the end of each of four arms of an eight‐arm radial maze. On completion of the radial maze task, the Fos expression in the hippocampus was examined immunohistochemically.3. Chronic DHA administration significantly reduced the number of reference and working memory errors. The number of Fos‐positive neurons in the CA1 hippocampus significantly increased in DHA‐treated rats compared with control rats, demonstrating a statistically significant negative correlation with the number of reference memory errors.4. These results suggest that the DHA‐induced improvement in spatial cognition is associated with increased Fos expression in the CA1 hippocampus.
Vascular gap junctions and implications for hypertension
Authors: Rummery Nicole M , Hill Caryl E 
Published: November 2004

Summary1. Four connexin (Cx) molecules, namely Cx37, Cx40, Cx43 and Cx45, are expressed in the gap junctions that exist within and between the cellular layers of arteries.2. Endothelial cells are well coupled by large gap junctions expressing Cx37, Cx40 and, to a lesser extent, Cx43, whose expression may be more subject to regulation by physical factors.3. Smooth muscle cells are more heterogeneously coupled by gap junctions that are small and rare. The identity of the Cx expressed in the media may vary among different arteries.4. Myoendothelial gap junctions are small and more common in resistance arteries with fewer layers of smooth muscle cells. Given the small size of these gap junctions and the rapid turnover rate of Cxs, homocellular coupling in the media and heterocellular coupling between the cell layers may be subject to more dynamic control than coupling in the endothelium.5. Vascular gap junctions have been implicated in a number of vasomotor responses that may regulate vascular tone and blood pressure. These include the mechanism of action of the vasodilator, endothelium‐derived hyperpolarizing factor (EDHF), the myogenic constriction to intramural pressure increase, the spontaneous or agonist‐induced vasomotion of arteries and arterioles and the spreading vasodilation and constriction observed in microcirculatory networks.6. Few data are available on Cx expression in the media of resistance arteries during hypertension. Changes in the expression of Cx43 described in the media of the aorta of hypertensive rats vary with the hypertensive model studied and are likely to represent adaptations to structural changes in the vascular wall.7. In contrast, in the endothelium of the caudal and mesenteric arteries of spontaneously hypertensive rats, expression of Cxs is significantly decreased compared with arteries from normotensive rats and this decrease is reversed by inhibitors of the renin–angiotensin system.8. During hypertension, the activity of EDHF is decreased in the mesenteric artery, but this occurs much later than the initial increase in blood pressure and the decrease in endothelial Cxs, suggesting that changes in EDHF may not be causally related to hypertension or to the changes in endothelial Cxs.9. Upregulation of the myogenic response and the incidence of vasomotion has been reported in hypertension. Little is currently known of the effects of hypertension on spreading vasomotor responses.10. Deletion of specific Cxs in genetically modified mice is complicated by neonatal lethality or coordinate regulation and compensatory changes in the remaining Cxs. Nevertheless, mice in which Cx40 has been deleted are hypertensive and spreading vasodilatory responses are significantly impaired.11. Determination of a role for specific Cxs in the control of blood pressure must await the development of animals in which Cx expression can be modulated in a more complex temporal and tissue‐specific manner.
Role of endogenous macrophage inflammatory protein‐2 in regulating fever induced by bacterial endotoxin in normal and immunosuppressed rats
Authors: Miñano Francisco J , Tavares Eva , Maldonado Rosario 
Published: November 2004

Summary1. During myelosuppressive chemotherapy, Gram‐negative bacterial infection with consequent exposure to lipopolysaccharide (LPS) is one of the most important causes of persistent fever.2. The classical model of the pathogenesis of fever suggests that pro‐inflammatory cytokines, produced by leucocytes in the bloodstream in response to exogenous pyrogens such as bacterial LPS, represent the distal mediators of the febrile response. Neutrophils are the first effectors cells and the most prominent leucocyte population involved in acute bacterial infection.3. Macrophage inflammatory protein (MIP)‐2 plays a crucial role in influencing early cell trafficking and neutrophil activation during pathophysiological processes and serves the same chemotactic function as human interleukin‐8.4. In the present study, we investigated the role of MIP‐2 in the development of a febrile response induced by LPS in immunocompetent and leukopenic rats.5. Intraperitoneal injection of LPS in leukopenic rats elicited a biphasic febrile response of rapid onset, the magnitude and duration of which were significantly greater than in immunocompetent animals. The febrile responses to LPS were accompanied by a pronounced induction of serum MIP‐2 levels at 1, 2 and 4 h compared with their respective controls.6. In both normal and leukopenic rats, neutralization of endogenous MIP‐2 bioactivity by systemic administration of antirat MIP‐2 antibody caused a significant attenuation of the early phase of LPS fever. However, in contrast with normal rats, the second phase of fever was unimpaired by anti‐MIP‐2 in leukopenic rats. These findings suggest that circulating MIP‐2 is involved in the generation of the early phase of LPS fever that contributes to the maintenance of the later phase of fever in immunocompetent, but not leukopenic, rats.7. Our data support a regulatory role for endogenous MIP‐2 in initiating the fever responses to LPS. Furthermore, these results provide evidence that different cellular and humoral mechanisms are implicated in the development of a febrile response triggered by Gram‐negative bacterial infections in leukopenic hosts.
Sulphur and skin: from Satan to Saddam!
Authors: Leslie K S , Millington G W M , Levell N J 
Published: November 2004

SummarySince the dawn of time, Beelzebub has been showering fire and brimstone (sulphur) on tortured souls, but the cutaneous effects of this have been poorly described.Sulphur has also been used for centuries as a treatment for many skin conditions, such as fungal infections, scabies, psoriasis, eczema and acne. It has also been used extensively in cosmetic preparations and by cosmetic dermatologists treating conditions such as seborrhoeic eczema. Many natural bathing spas have high levels of sulphur; such balneology has been advocated by medical and cosmetic dermatologists as an effective treatment for cutaneous disorders for more than 500 years. Sulphur was often the active agent in many of the so‐called ‘patent medicines’ that became popular in the mid‐nineteenth century.Time has not withered medical practitioners’ enthusiasm for sulphur. There are various reports in the medical literature of its current use. However sulphur treatment is not without its risks; a sulphur spring dermatitis has been described from a spa bath in Taiwan. With the satanic threat of bio‐terrorism, some dermatologists may be treating the effects of contact with sulphur mustard all too soon.
Smoking can be good for you
Authors: Wolf R , Orion E , Matz H , Maitra S , Rowland‐Payne C 
Published: November 2004

SummarySmoking is without doubt one of the greatest causes of avoidable illness and death in the modern world. Most well known is the relationship between smoking and numerous cancers, cerebrovascular and cardiovascular disease.Smoking and most especially nicotine, are, however, sometimes beneficial in certain diseases, including Parkinson's, Alzheimer's, allergic alveolitis, nausea and vomiting of pregnancy, pre‐eclampsia, fibroids, carcinoma of body of uterus, ulcerative colitis, pyoderma gangrenosum, aphthous stomatitis and ulceration, pemphigus, herpes simplex and acne.In the immensely justifiable enthusiasm to discredit this dangerous activity, the mechanisms behind these beneficial effects tend to have been un‐discussed or ignored.It is the aim of this paper to spur interest in the reasons for these effects. If the mechanisms are elucidated, therapeutic advances may be possible.
Patapius spinosus: First record of Leptopodidae (Heteroptera) from Japan
Authors: YAMAZAKI Kazuo , SUGIURA Shinji 
Published: November 2004

Abstract Patapius spinosus, a remarkable leptopodid bug whose body is covered with spines, was collected for the first time in Japan. This species was found in the supralittoral zone of a sandy beach in Osaka Prefecture, central Japan, in autumn 2002 and in spring 2004. Patapius spinosus is known to be distributed in the Mediterranean and North African regions, and has been introduced into North America and Chile. Its occurrence in Japan could signify either an eastern limit of its native distribution or an exotic origin.
Faunal make‐up, host range and infestation rate of weevils and tephritid flies associated with flower heads of the thistle Cirsium (Cardueae: Astaraceae) in Japan
Authors: NAKAMURA Akinori , NAKAMURA Koji 
Published: November 2004

AbstractFrom 1988 to 1998, we collected flower heads of 39 thistle taxa (35 taxa of Cirsium, one species each of Breea, Synurus, Saussurea and Arctium; Cardueae; Astaraceae) in Japan, mainly from Hokuriku and other parts of central Honshu, and kept them in the laboratory to breed weevils and tephritid flies, the core fauna. We report the faunal make‐up, host plants, geographic distribution and the attack levels of the insects. Results indicated that (i) three Larinus species (Curculionidae) and three species of tephritid flies (Tephritis, Urophora and Xyphosia) comprised the core fauna; (ii) two insect species belonging to the same taxonomic group (either Curculionidae (Larinus) or Tephritidae) tended to use different host plant species; (iii) two sympatric Larinus species (L. latissimus and L. meleagris) segregated the host plants seasonally in central Honshu (Cirsium blooming in spring and autumn, respectively); and (iv) two tephritid fly species, Xyphosia punctigera and Urophora sachalinensis, segregated geographically (the former on the Japan Sea side and the latter on the Pacific Ocean side). In comparison with their European counterparts, the weevils and tephritids of the Japanese Cirsium are characterized by a lower species richness and a lower degree of specialization in usage of the thistle flower heads, with gall‐formers being distinctly under‐represented, and callus tissue‐feeders being absent. This reflects the fact that Japanese thistles are so closely related that hybridization frequently occurs, and also that the thistles have had a short history of interaction with the insects since the thistles’ arrival in Japan.
Cryptically dimorphic caste differences in a Neotropical, swarm‐founding paper wasp genus, Parachartergus (Hymenoptera: Vespidae)
Authors: SAITO Fuki , MURAKAMI Takahiro , KOJIMA Jun‐ichi 
Published: November 2004

AbstractMorphological differences in body shape between females of different reproductive conditions (in terms of insemination and ovarian development) were examined in two species of the Neotropical polistine genus Parachartergus: P. smithii and P. fraternus. The present study shows, for the first time, that non‐size‐based morphological divergence between queens and workers occurs in Parachartergus, an epiponine genus once believed to have little or no morphological caste differences. In the P. smithii colony examined, queens were significantly larger than workers in five of the eight body parts measured (head width, eye width, genal width, mesosomal length, wing length, first metasomal tergum width, and width and length of the second tergum), but the mean values of wing length and first and second tergum widths were not significantly different between them. The queen : worker size ratios tended to be greater anteriorly and smaller posteriorly, although the size ratio was greatest in second tergum length. Analysis of covariance (ancova) with mesosomal length as covariate showed that queens had proportionally wider heads and narrower first terga than did workers. In the P. fraternus colony, size differences between queens and workers were not significant, and there was little or no difference in shape, but queens had significantly proportionally wider first terga than did workers.