bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a large parallel‐cable manipulator for the feed‐supporting system of a next‐generation large radio telescope
Authors: Su Y. X. , Duan B. Y. , Nan R. D. , Peng B.
Published: October 2004

A large parallel‐cable manipulator for the feed‐supporting system of a next‐generation large radio telescope is presented in this paper. The approximate kinematics model of the system is developed to improve real‐time controllability, and the rationality of this approximation is validated by a kinematics accuracy analysis. In order to guarantee the effectiveness of control, the singularity of the large parallel‐cable manipulator is analyzed (including kinematics and force singularities). The control strategy of the parallel‐cable feed‐supporting system is also proposed. © 2001 John Wiley & Sons, Inc.
An immune network with interactions between B cells for pattern recognition
Authors: Tashima Koichi , Tang Zheng , Ishizuka Okihiko , Tanno Koichi
Published: October 2004

In this paper the authors propose an immune network which considers B cell interactions based on the immune response network of an organism. The authors modeled a network based on an immune mechanism which uses B cell interactions for an immune response network with interactions between B cells and T cells in an organism. They then created an immune network. Finally, the authors describe the validity of pattern recognition using their immune network by performing simulations on the proposed network. © 2001 Scripta Technica, Syst Comp Jpn, 32(10): 31–41, 2001
A slice reduction method using function activation information
Authors: Nishimatsu Akira , Jihira Minoru , Kusumoto Shinji , Inoue Katsuro
Published: October 2004

During debugging or maintenance of large‐scale software, it is useful to be able to restrict the reference range to a part of the program rather than reference the entire program. Program slicing has been proposed as a method to restrict the reference range. A static slice extracts the set of statements that can affect the values of the variables being watched. In many cases, however, the slices include parts that are in fact unrelated, and so the reference range cannot be sufficiently restricted. On the other hand, a dynamic slice can sufficiently restrict the reference range by actually executing the program and then using the dynamic information thus obtained to extract the set of statements which, when executed, may have an effect on the value of the variables being watched. However, considerable time and space are required in order to obtain the dynamic information during program execution. In this paper the authors propose a program slice extraction method which combines the small amount of dynamic information obtained by executing the program with static analysis. Slices extracted using this method are referred to as Call‐Mark slices. When calculating a Call‐Mark slice, first the data dependence relationship and the control dependence relationship in the program are analyzed in a static manner, then the procedures and function call memory during program execution are stored. Then, by clarifying the dynamic dependence relationship in the variables from the above information, slices can be collected more efficiently than in conventional approaches. In addition, the authors use the Call‐Mark slice in a slicing system that was previously developed, and then evaluate its validity. © 2001 Scripta Technica, Syst Comp Jpn, 32(10): 59–68, 2001
Role of endoscopy in staging colorectal cancer
Authors: Frascio Flavio , Giacosa Attilio
Published: October 2004

The treatment of colorectal cancer depends in large measure on the depth of tumor invasion and the extent of lymph node involvement. Endoscopic ultrasonography (EUS) has added a new dimension to the evaluation of tumor invasion and lymph node involvement in gastrointestinal cancer. The overall EUS accuracy for colorectal cancer T‐staging is 78%, specificity is 73%, and sensitivity is 94%. In determining the nodal involvement by tumor, EUS has an accuracy of 75%, specificity of 73%, and sensitivity of 74%. Comparison with computerized tomography (CT), magnetic resonance imaging (MRI), and MRI with endorectal coil (MRIEC) shows that EUS is an effective single modality for assessing tumor penetration of the rectal wall. It does not, however, allow the assessment of distant metastatic disease. For assessing lymph node involvement, MRIEC offers the most comprehensive information. Semin. Surg. Oncol. 20:82–85, 2001. © 2001 Wiley‐Liss, Inc.
Role of video‐laparoscopy in the staging of intra‐abdominal lymphomas and gastrointestinal cancer
Authors: Cuschieri Alfred
Published: October 2004

There is good category II/III evidence that video‐laparoscopic staging is valuable in certain gastrointestinal (gastric, esophageal, pancreatic, and hepatobiliary) and intra‐abdominal lymphomas, but no category I evidence (based on prospective randomized trials). The evidence available is all retrospective, but of sufficient consistency to indicate that laparoscopic staging adds to the primary (imaging) staging and often alters the clinical stage of the disease and hence the management of the individual patient. The advent of laparoscopic contact ultrasound (LCU) scanning has improved the staging accuracy for pancreatic and hepatobiliary neoplasms. The laparoscopic approach also offers a means of surgical palliation in certain patient groups. However, there are a number of unresolved issues concerning the use of video‐laparoscopy. The most important concerns whether staging laparoscopy should be performed immediately before scheduled surgery or as a separate intervention. The cost‐efficacy of these two management options needs to be evaluated in prospective studies. In some centres, laparoscopic staging is being conducted by gastroenterologists and hepatologists. This raises issues of safety and ability to undertake certain procedures that may be necessary during the laparoscopic staging. Semin. Surg. Oncol. 20:167–172, 2001. © 2001 Wiley‐Liss, Inc.
MHC class I and II antigen expression and interferon α treatment of human midgut carcinoid tumors
Authors: Makridis C. , Juhlin C. , Åkerström G. , Öberg K. , Rastad J.
Published: October 2004

Cryosections of 28 primary and metastatic midgut carcinoid tumors from 12 patients with carcinoid syndrome were investigated immunohistochemically with antibodies that recognize human MHC class I (HLA‐ABC) and class II (HLA‐DR) antigens. The tumor parenchyma of all six patients treated with interferon α (IFN‐α) during a mean 8.6 months (3x106 to 5x106 U three times weekly) exhibited unequivocal HLA‐ABC immunoreactivity, with only minor discrepancies between primary lesions and metastases in mesenteric lymph nodes and liver. Class I staining was absent on the tumor cells of all 14 specimens from the patients without IFN therapy but was induced by culturing freshly dispersed tumor cells in vitro for 48 hours in the presence of recombinant IFN‐α. The stroma of all neoplasms displayed class I and II immunostaining, as did usually a few CD4‐expressing cells. The carcinoid specimens lacked parenchymal HLA‐DR immunoreactivity, which is interesting considering suggestions on improved prognosis for bowel carcinomas lacking the class II expression. The study supports the idea that induction of MHC class I antigens could contribute to the beneficial clinical effects of IFN‐α treatment in patients with midgut carcinoid tumors.
Surgical management of insulinoma associated with multiple endocrine neoplasia type I
Authors: O'Riordain Diarmuid S. , O'Brien Timothy , van Heerden Jon A. , Service F. J. , Grant Clive S.
Published: October 2004

Insulinoma in patients with multiple endocrine neoplasia (MEN) is a rare condition that because of its usual multicentricity presents difficulties not encountered in sporadic patients. In contrast to gastrinoma, which is the most common pancreatic neoplasm associated with MEN I, malignancy and duodenal tumors are much less common for patients with insulinomas, and excellent palliative medication is not available. Accordingly, there is a much greater reliance on surgical therapy for this group of patients. Between 1970 and 1991 a total of 19 patients had surgical treatment of MEN I‐related insulinoma. Each patient had hyperinsulinemic hypoglycemia. One patient, with extensive metastases, had unresectable disease. Of the remaining 18, there were 16 (89%) multiple pancreatic tumors. Tumors were located in the neck, body, or tail in 17 cases, 10 of whom also had tumors in the head. Pancreatic resections performed were 1 total, 12 subtotal (7 also had enucleation of tumors from the pancreatic head), and 5 limited distal resections and/or enucleation (conservative resection). There was no operative mortality. One patient developed pancreatitis, fistula, and diabetes following subtotal resection and enucleation. Postoperative cure was achieved in 17 of 18 cases. Recurrent disease occurred in 2 of 5 conservative resections compared to 0 of 12 subtotal resections, with median follow‐up times of 10.4 and 10.3 years, respectively. During the follow‐up period, four patients died, possibly all due to MEN I‐related conditions. Hyperinsulinism in MEN I is associated with the occurrence of multiple, usually benign, pancreatic islet cell tumors, and surgery is an effective treatment modality. Surgical management should be guided by two principles: total removal of gross disease and safe prophylactic pancreatic resection. Acceptable morbidity, low recurrence rates, and a low risk of inducing diabetes lead us to recommend routine subtotal distal pancreatectomy. Meticulous evaluation of the pancreatic head using intraoperative ultrasonography to locate tumors and to locate the pancreatic duct, followed by precise enucleation of residual tumors, is essential to ensure cure.
Expression of basic fibroblast growth factor in thyroid disorders
Authors: Shingu Kiyoshi , Sugenoya Akira , Itoh Nobuo , Kato Ryoji
Published: October 2004

Morphologic and biologic studies were undertaken to clarify the biologic significance of basic fibroblast growth factor (bFGF) in human thyroid neoplasms. A total of 71 malignant tumors (50 papillary carcinomas, 14 follicular carcinomas, 7 anaplastic carcinomas), 11 follicular adenomas, 6 adenomatous goiters, and 6 Graves' disease tissues were examined employing immunohistochemical methods (avidin‐biotin‐peroxidase complex technique). An affinity‐purified polyclonal rabbit antiserum to human bFGF was used as a primary antibody. The eluate of malignant thyroid tumor tissues from the heparin‐Sepharose column was examined by Western blot analysis to elucidate the molecular weight form. With immunohistochemical staining, bFGF was frequently detected in the cytoplasm of malignant thyroid tumors compared to tissues of the benign diseases and normal controls. With anaplastic carcinoma, immunoreactivity of the tumor cells was particularly strong. In the correlative analyses between UICC TNM classification and bFGF staining in papillary carcinoma, there were significant differences when relating positive staining to the grade of nodal metastases. By Western blot analysis, the bFGF immunoreactivity was specifically detected in the two forms, with molecular weights of 18 and 33 kDa. The high‐molecular‐weight form was detected in only anaplastic carcinoma. The present investigations demonstrated a close correlation between the expression of bFGF and the degree of malignancy. bFGF might play an important role in promoting lymph node metastases. Moreover, the high‐molecular‐weight form of bFGF might have an intense influence on tumor growth.
Significance of P53 in human thyroid tumors
Authors: Simon Dietmar , Goretzki Peter E. , Goreley Victor , Ebling Birgit , Reishaus Ellen , Lyons John , Haubruck Hans , Röher Hans D.
Published: October 2004

Mutational changes in the p53 tumor suppressor gene are the most frequent genetic alterations in human malignant tumors. Studies have shown a correlation of p53 expression in breast cancer with tumor prognosis. In contrast to mutational activation of ras and GSP in thyroid tumors, little is known about the role of p53 in thyroid tumor development. Therefore thyroid tumors and thyroid tumor cell lines were studied for the presence of p53 mutations. Snap‐frozen tissues from 57 differentiated thyroid carcinomas (DTCs) and 5 goiters were studied by immunohistochemical methods. A panel of six antibodies (pAb 240, 421, 1620, 1801, DO7, and CM1) was employed by using the ABC technique. Five cell lines from DTCs (FTC133, 236, 238, PTC337, MTC164) were examined by the same technique. Additionally, genomic DNA from the cells was amplified by the polymerase chain reaction (PCR) and the PCR product studied for p53 mutations (R273H) by mutation‐specific oligonucleotide hybridization (MOH) and temperature gradient gel electrophoresis (TGGE) for the p53 exon 8. None of the benign thyroid tumors and 7 of 57 (12%) DTCs strongly express p53 with a heterogeneous distribution in the tumor tissue. All seven patients have metastatic disease or dedifferentiated tumors G3 (three of seven). CM1 was positive in two cell lines (FTC‐133, PTC‐337), questionable in FTC‐238, and negative in FTC‐236 and MTC‐164. All three follicular cell lines, however, and the original tumor tissue showed the same p53 mutation (R273H) in MOH analysis and TGGE. P53 mutations are rare in thyroid tumors, but the presence of p53 mutations indicates a poor prognosis. TGGE seems to be a sensitive method for detecting p53 mutations (1% sensitivity) and might play a role in tumor screening in the future.
Multivariate analysis of risk factors influencing survival in 110 ethnic Chinese with papillary thyroid cancer
Authors: Lorentz Theo G. , Lau Peter W. K. , Lo Chung Y. , Law Wai L. , Wan Koon Y. , Lauder Ian J.
Published: October 2004

Data from 110 Chinese patients presenting with papillary thyroid cancer to a single institution up to December 1985 have been analyzed to evaluate the possible risk factors affecting survival. There were 83 women and 27 men with an age range of 15 to 78 years (mean 45 years, median 42 years). The longest follow‐up period is 39 years and the median 10 years. Cervical lymph node recurrence more than 6 months after surgery developed in 12 patients, of whom 1 died with a concomitant distant metastasis. “Thyroid bed” tumor recurrence, after apparently complete surgery, presented in 10 patients and resulted in 5 deaths. Distant metastases were identified in 17 patients with 7 deaths. Another 4 patients died from advanced local disease incompletely resectable on presentation. The following seven risk factors for survival were selected for multivariate analysis: age, sex, tumor size, histologic evidence of extrathyroidal spread, lymph node recurrence, neck recurrence, and distant metastases. Age, size, neck recurrence, and distant metastases were all significant on univariate analysis. Using Cox proportional hazards regression in the multivariate analysis of these seven factors, only age (p<0.0001) was shown to be significant. Age over 40 years on first diagnosis was a highly significant indicator of high risk (p=0.0003, log‐rank).
Expression of proliferating cell nuclear antigens in parathyroid glands of renal hyperparathyroidism
Authors: Ohta Kikuko , Manabe Toshiaki , Katagiri Makato , Harada Tanekazu
Published: October 2004

Total parathyroidectomy with autotransplantation of a small piece of the resected hyperplastic gland is currently the usual surgical procedure for renal hyperparathyroidism in Japan. Empirically, the smallest glands showing diffuse growth are selected for the graft. In order to seek the rationale for this procedure, we examined 50 cases of both nodular and diffuse hyperplastic parathyroid glands and five cases of recurrent grafted tissues histologically and immunohistochemically with anti‐proliferating cell nuclear antigen (PCNA) antibody. The proliferative activity of the glands growing in diffuse fashion was much lower than that of those growing in nodular fashion (p<0.05). All the parathyroid glands selected for grafting in the recurrent cases showed nodular growth. No relation was revealed between PCNA expression and the size of the glands, or between the former and the type of cell components (chief and oxyphilic cells). In nodular lesions, immunopositive cells were frequently distributed near the thick fibrous capsule. From these results, we conclude that parathyroid glands showing a diffuse growth pattern are indeed suitable for the graft. When only a nodular hyperplastic parathyroid gland is available, it is suggested that the central portion of the nodule may provide a better source for the graft with little chance of recurrence.
Successful allotransplantation of microencapsulated parathyroids in rats
Authors: Hasse Christian , Schrezenmeir Jürgen , Stinner Benno , Schark Claudia , Wagner Peter K. , Neumann Kurt , Rothmund Matthias
Published: October 2004

Allotransplantation of parathyroid tissue in humans is desirable for treating long‐term hypoparathyroidism (e.g., after inadvertent removal of parathyroid glands during thyroid surgery). Until now, parathyroid allotransplantation was not used clinically because its advantages were outweighted by the need of immunosuppression. To overcome the immunogenicity of the tissue to be transplanted, we employed the method of microencapsulation; first tried in islet cell transplantation for experimental allotransplantation of parathyroid tissue. We have been able to achieve long‐term success in a rat model. After isolation and tissue culture, tissue pieces from parathyroid glands of 280 Lewis rats were encapsulated in barium alginate and grafted into hypocalcemic DA rats. From the 7th to the 90th day after transplantation the recipient rats (DA rats) showed a normal serum calcium concentration. This is the first report of successful long‐term survival and function of microencapsulated allotransplanted parathyroid tissue.
Two novel mutations in the β‐myosin heavy chain gene associated with dilated cardiomyopathy
Authors: Kärkkäinen Satu , Heliö Tiina , Jääskeläinen Pertti , Miettinen Raija , Tuomainen Petri , Ylitalo Kari , Kaartinen Maija , Reissell Eeva , Toivonen Lauri , Nieminen Markku S. , Kuusisto Johanna , Laakso Markku , Peuhkurinen Keijo
Published: October 2004

Background:

Dilated cardiomyopathy (DCM) is familial in approximately 20–35% of cases of idiopathic DCM. Several mutations in the different sarcomere protein genes have been reported to cause DCM.

Aims:

We wanted to investigate the role of sarcomere protein gene variants in Finnish DCM patients.

Methods and results:

We screened all coding exons of five sarcomere protein genes (β‐myosin heavy chain, α‐tropomyosin, troponin C, troponin I and troponin T) in a well‐characterized population of 52 DCM patients in Eastern Finland by the PCR‐SSCP and sequencing method. Two novel mutations, Arg1053Gln and Arg1500Trp, in the β‐myosin heavy chain gene in two index patients were detected. The proband with the Arg1053Gln mutation had a dilated left ventricle and impaired systolic function, but other family members carrying this mutation presented with septal hypertrophy. It thus seems that the Arg1053Gln mutation is primarily a HCM mutation, which can also lead to DCM. The other mutation, Arg1500Trp, was associated with a typical DCM phenotype. The Arg1500Trp mutation carrier had only one family member alive, but she did not carry the mutation and, therefore, cosegregation of the mutation and the disease in this family could not be reliably verified. No disease‐causing mutations were found in the other sarcomere protein genes.

Conclusions:

Two novel mutations in the β‐myosin heavy chain gene were detected in patients with DCM. Overall, mutations in the β‐myosin heavy chain gene seem to be relatively uncommon in Finnish DCM patients.
Managing Atlantic salmon (Salmo salar L.) in the mixed stock environment: challenges and considerations
Authors: Crozier W.W. , Schön P-J. , Chaput G. , Potter E.C.E. , Maoiléidigh N.Ó , MacLean J.C.
Published: October 2004

Atlantic salmon, as a result of their population structure and behaviour, are potentially subject to a complex array of fisheries, ranging from those within rivers harvesting single stocks, to distant-water mixed stock fisheries that harvest fish from different countries, stock complexes, and continents. In addition, estuarine and in-river fisheries may catch fish from more than one stock or stock component, where these are present. One of the main challenges in managing salmon across this range of fisheries is to account for the differing status of stocks with respect to safe biological limits, noting that stocks of differing productivity may require different harvest strategies. Also, the existence of sequential harvest in different fisheries provides unique challenges, because decisions in an individual fishery cannot be made in isolation of the impacts of other fisheries on those stocks. We illustrate the uncertainties and complexities involved in managing mixed stocks of salmon, whether in home-waters or in distant-water fisheries, and examples are given to illustrate how science and management are, or should be, developing to face these challenges.
Developing and refining a joint management procedure for the multispecies South African pelagic fishery
Authors: De Oliveira J.A.A. , Butterworth D.S.
Published: October 2004

Pilchard (sardine) and anchovy are the main targets of South Africa's pelagic fishery. This fishery is the country's second most valuable in monetary terms, and produces the highest annual yield in terms of landed mass (in recent years, a combined catch of the order of 400 000 t). It is the most dynamic of South Africa's main commercial fisheries, because the species targeted are relatively short-lived, often occur in mixed shoals, and experience large fluctuations in abundance. Mixed shoaling causes operational problems for the fishery, because of the inevitability of juvenile pilchard bycatch (of more value as adults for canning) in the anchovy-directed fishery. This operational interaction implies a trade-off between allowable catches for the two species, and hence necessitates that they are managed together. The development of a joint “management procedure” (sensu IWC) for the two species is described. This provides a framework for quantifying this trade-off, subject to the constraint that acceptable levels of risk of “collapse” are not exceeded for either resource. Important new features incorporated in a revision of the procedure implemented in 2002, which have made appreciably enhanced catches from the resources possible, are described.
Climate variability at the southern boundaries of the Namib (southwestern Africa) and Atacama (northern Chile) coastal deserts during the last 120,000 yr
Authors: Stuut Jan-Berend W. , Lamy Frank
Published: October 2004

In this study, we present grain-size distributions of the terrigenous fraction of two deep-sea sediment cores from the SE Atlantic (offshore Namibia) and from the SE Pacific (offshore northern Chile), which we "unmix" into subpopulations and which are interpreted as coarse eolian dust, fine eolian dust, and fluvial mud. The downcore ratios of the proportions of eolian dust and fluvial mud subsequently represent paleocontinental aridity records of southwestern Africa and northern Chile for the last 120,000 yr. The two records show a relatively wet Last Glacial Maximum (LGM) compared to a relatively dry Holocene, but different orbital variability on longer time scales. Generally, the northern Chilean aridity record shows higher-frequency changes, which are closely related to precessional variation in solar insolation, compared to the southwestern African aridity record, which shows a remarkable resemblance to the global ice-volume record. We relate the changes in continental aridity in southwestern Africa and northern Chile to changes in the latitudinal position of the moisture-bearing Southern Westerlies, potentially driven by the sea-ice extent around Antarctica and overprinted by tropical forcing in the equatorial Pacific Ocean.
A mixed-feedingEquusspecies from the middle pleistocene of South Africa
Authors: Kaiser Thomas M. , Franz-Odendaal Tamara A.
Published: October 2004

The dietary regime ofEquus capensisfrom the Middle Pleistocene of South Africa is investigated by mesowear analysis. Results indicate that the mesowear signature of this species resembles that of two extant mixed feeders, the Grant's Gazelle (Gazella granti) and the Thomson's Gazelle (Gazella thomsoni), suggesting a mixed feeding dietary strategy forE. capensis. The mesowear signature of a contemporaneous population ofEquus mosbachensisfrom Europe (Arago, France) is also determined for comparative purposes and has a typical grazing signature. In general, all extant species ofEquusare believed to be almost exclusively grazers. However, a considerable degree of dietary flexibility is recently reported. The dietary signal ofE. capensisis considered to be the result of feeding on the unique fynbos vegetation, which was beginning to establish itself at this time in southwestern South Africa. Grasses are a minor component of this floral kingdom. Our findings thus provide further evidence for the unexpected flexibility in feeding strategies ofEquus, the most widely distributed equid taxon in the Quaternary. They highlight the potential use of the attrition"abrasion wear equilibrium as a habitat indicator, by mirroring the availability of food items in mammalian herbivore ecosystems.
Therapie der Fahreignung in der Klinischen Neuropsychologie
Authors: Schale Andreas
Published: October 2004

Zusammenfassung: In dieser Arbeit sollen wichtige Aspekte der Therapie der Fahreignung in der klinischen Neuropsychologie einer näheren Betrachtung unterzogen werden. Eine tragfähige Beziehung zwischen Patient und Therapie sowie die Einbeziehung weiterer psychotherapeutischer Elemente können wichtige Bedingungen zur Behandlung dieses sensiblen Bereiches sein. In der Therapie nimmt die Motivierung des Patienten zur Abklärung seiner Fahreignung einen zentralen Stellenwert ein. Der erste Schritt dafür ist eine auf den Patienten und seine Erkrankung abgestimmte Aufklärung über die rechtlichen Rahmenbedingungen der Fahreignung. Dabei gilt es, eine Therapiemotivation aufzubauen und den Patienten für eine informelle oder amtliche Abklärung seiner Fahreignung zu gewinnen. Nach einer neuropsychologischen Untersuchung der fahrrelevanten Leistungsfähigkeit und/oder einer Fahrverhaltensprobe bzw. eines Fahrtrainings erfolgt dann die Erarbeitung von Konsequenzen aus den jeweiligen Ergebnissen. Die Behandlung der Fahrfähigkeit selbst kann ein neuropsychologisches Funktionstraining fahrrelevanter kognitiver Leistungen, die Erarbeitung von Kompensationsstrategien, die Festlegung möglicher Auflagen/Beschränkungen sowie ein individuelles Fahrtraining beinhalten. Diagnostik und Therapie der Fahreignung bei hirngeschädigten Patienten erfordern die speziellen Kenntnisse des Klinischen Neuropsychologen, dessen Kompetenz bei zukünftigen gesetzgeberischen Vorhaben sowie der Entwicklung und Umsetzung von Behandlungsmodellen unbedingt berücksichtigt werden muss.
Factor Structure and Reliability of the Anxiety Sensitivity Profile in a Turkish Sample1
Authors: Ayvasik H. Belgin , Tutarel-Kislak Sennur
Published: October 2004

Summary: Anxiety sensitivity is an individual difference variable defined as the fear of fear or the fear of anxiety, arising from the belief that the experience of anxiety symptoms leads to illness or additional anxiety. The Anxiety Sensitivity Profile (ASP) is a 60 item self-report measurement, and each item is assessed on a 7-point scale. The purpose of this study is to determine the factor structure and reliability of the Turkish version of the ASP. To address this purpose, first the scale was translated into Turkish, and then it was administered to 434 university students. Principal components factor analysis with promax rotation revealed four factors in which all items had a factor loading of 0.30 or more. The factors were as follows: (1) fear of respiratory symptoms, (2) fear of cognitive dyscontrol, (3) fear of cardiac symptoms, and (4) fear of gastrointestinal symptoms. The internal consistency of these four factors was 0.97, 0.93, 0.91, and 0.86, respectively. The overall scale also had a high degree of internal consistency, with an α coefficient of 0.98. Item-total analysis revealed that the internal consistency of all items was satisfactory (rs 0.30-0.77). Data provided evidence that the Turkish version of the ASP had a multidimensional construct with four lower order factors loaded on a higher order factor.
Modeling temporal variability of plasma conditions in the Io torus during the Cassini era
Authors: Delamere P. A. , Steffl A. , Bagenal F.
Published: October 2004

Observations of ultraviolet (UV) emissions from the major ion species (S+, S++, S+++, O+, O++) of the Io plasma torus made during the Cassini flyby (October 2000 to March 2001) have revealed significant time variability. Using a homogeneous model for mass and energy flow in the torus parameterized by five input variables (transport timescale, neutral source strength, ratio of oxygen to sulfur atoms in the source, fraction of superthermal electrons, and temperature of the hot electrons), we have investigated the time variability of the torus properties (density, composition, and temperature) during the Cassini era. In order to match the changes in emissions, the model suggests that a significant change in the neutral source occurred near the beginning of the observing period, decreasing from >1.8 tons/s to 0.7 tons/s. The changes in the neutral source appear to coincide with the declining phase of a dramatic (i.e., 2–3 order of magnitude) peak in iogenic dust emissions observed by Galileo prior to the Cassini era.
Imaging the source region of the 2003 San Simeon earthquake within the weak Franciscan subduction complex, central California
Authors: Hauksson Egill , Oppenheimer David , Brocher Thomas M.
Published: October 2004

Data collected from the 2003 Mw6.5 San Simeon earthquake sequence in central California and a 1986 seismic refraction experiment demonstrate that the weak Franciscan subduction complex suffered brittle failure in a region without significant velocity contrast across a slip plane. Relocated hypocenters suggest a spatial relationship between the seismicity and the Oceanic fault, although blind faulting on a nearby, unknown fault is an equally plausible alternative. The aftershock volume is sandwiched between the Nacimiento and Oceanic faults and is characterized by rocks of low compressional velocity (Vp) abutted to the east and west by rocks of higher Vp. This volume of inferred Franciscan rocks is embedded within the larger Santa Lucia anticline. Pore fluids, whose presence is implied by elevated Vp/Vs values, may locally decrease normal stress and limit the aftershock depth distribution between 3 to 10 km within the hanging wall. The paucity of aftershocks along the mainshock rupture surface may reflect either the absence of a damage zone or an almost complete stress drop within the low Vp or weak rock matrix surrounding the mainshock rupture.
O/N2 changes during 1–4 October 2002 storms: IMAGE SI‐13 and TIMED/GUVI observations
Authors: Zhang Y. , Paxton L. J. , Morrison D. , Wolven B. , Kil H. , Meng C.‐I. , Mende S. B. , Immel T. J.
Published: October 2004

Thermospheric O/N2 column density ratios referenced at a N2 column density of 1017 cm−2 are obtained using the IMAGE SI‐13 and TIMED/GUVI far‐ultraviolet (FUV) dayglow data, AURIC simulation results, and MSIS86 model. Each of the magnetic storms occurring during a 4‐day period (1–4 October 2002) caused significant O/N2 depletion that was detected by both of the IMAGE SI‐13 and GUVI instruments. The depletion extended down to latitudes of 10° and −5° in the Northern and Southern Hemispheres, respectively. Simultaneous measurements show an excellent agreement between the SI‐13 and GUVI O/N2 on both global and local scales. The IMAGE SI‐13 O/N2 data provide direct optical evidence that the O/N2 depletion corotates with the Earth. The GUVI O/N2 indicate the depletion in both of the hemispheres is not symmetric owing to the seasonal effect and differences in heating and convection induced winds. Both the IMAGE SI‐13 and GUVI O/N2 maps also provide a good opportunity for future modeling efforts.
Anti‐inflammatory effects of nitric oxide‐releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis
Authors: Hyun Eric , Bolla Manlio , Steinhoff Martin , Wallace John L , Del Soldato Piero , Vergnolle Nathalie
Published: October 2004

The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide‐releasing anti‐inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti‐inflammatory benefits of conventional anti‐inflammatory drugs.

Since hydrocortisone is the most widely used anti‐inflammatory drug for the treatment of skin inflammation, we compared the anti‐inflammatory effects of hydrocortisone to an NO‐releasing derivative of hydrocortisone, NCX 1022, in a murine model of irritant contact dermatitis, induced by epidermal application of benzalkonium chloride.

Topical pre‐ and post‐treatment with NCX 1022 (3 nmol) in C57BL6 mice not only reduced ear oedema formation in a dose‐dependent manner, but also was significantly more effective than the parent compound during the initial stages of inflammation (from 1 to 5 h). NCX 1022, but not hydrocortisone, significantly inhibited granulocyte recruitment (tissue myeloperoxidase activity). Histological samples of mouse ears treated with NCX 1022 showed significant reduction in both the number of infiltrated cells and disruption of the tissue architecture compared to hydrocortisone‐treated tissues.

With intravital microscopy, we observed that both pre‐ and post‐treatments with NCX 1022 were more effective than hydrocortisone in terms of inhibiting benzalkonium chloride‐induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter.

These results suggest that by releasing NO, NCX 1022 modulates one of the early events of skin inflammation: the recruitment of leukocytes to the site of inflammation. Overall, we have shown that NO‐hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound.

British Journal of Pharmacology (2004) 143, 618–625. doi:10.1038/sj.bjp.0705854
The melanocortin receptor subtypes in chicken have high preference to ACTH‐derived peptides
Authors: Ling Maria K , Hotta Eri , Kilianova Zuzana , Haitina Tatjana , Ringholm Aneta , Johansson Lisa , Gallo‐Payet Nicole , Takeuchi Sakae , Schiöth Helgi B
Published: October 2004

Melanocortin (MC) receptors are widely distributed throughout the body of chicken, like in mammals, and participate in a wide range of physiological functions.

To clarify the pharmacological impact of ligands acting in the MC system, we expressed the chicken MC1, MC2, MC3, MC4 and MC5 (cMC1–5) receptors in eukaryotic cells and performed comprehensive pharmacological characterization of the potency of endogenous and synthetic melanocortin peptides.

Remarkably, the cMC receptors displayed high affinity for ACTH‐derived peptides and in general low affinity for α‐MSH. It is evident that not only the cMC2 receptor but also the other cMC receptors interact with ACTH‐derived peptide through an epitope beyond the sequence of α‐MSH.

The synthetic ligand MTII was found to be a potent agonist whereas HS024 was a potent antagonist at the cMC4 receptor, indicating that these ligands are suitable for physiological studies in chicken.

We also show the presence of prohormone convertase 1 (PC1) and PC2 genes in chicken, and that these peptides are coexpressed with proopiomelanocortin (POMC) in various tissues.

British Journal of Pharmacology (2004) 143, 626–637. doi:10.1038/sj.bjp.0705900
Inhibition of TRPM2 function by PARP inhibitors protects cells from oxidative stress‐induced death
Authors: Miller Barbara A
Published: October 2004

TRPM2 is a member of the transient receptor potential (TRP) protein superfamily of calcium‐permeable, voltage‐independent ion channels expressed in nonexcitable cells. Activation of TRPM2 by oxidative stress results in calcium influx and susceptibility to cell death, whereas inhibition of TRPM2 function enhances cell survival. In the present edition of this journal, Fonfria et al. demonstrate a role for poly(ADP ribose) polymerase (PARP) as a mediator between oxidative stress and TRPM2 activation. They present evidence that inhibition of either PARP or TRPM2 protects cells from plasma membrane damage and cell death. The therapeutic implications of this important observation are discussed.

British Journal of Pharmacology (2004) 143, 515–516. doi:10.1038/sj.bjp.0705923
G protein activation and cyclic AMP modulation by naloxone benzoylhydrazone in distinct layers of rat olfactory bulb
Authors: Onali Pierluigi , Olianas Maria C
Published: October 2004

Naloxone benzoylhydrazone (NalBzoH) has initially been developed as an agonist of the pharmacologically defined κ3‐opioid receptor and has recently been employed as an antagonist at the opioid receptor‐like (ORL1) receptor. In the present study, we investigated the ability of NalBzoH to elicit agonist‐like effects on receptor signalling in distinct layers of rat olfactory bulb, a brain region where we have demonstrated the presence of opioid and ORL1 receptors coupled to both stimulation and inhibition of cyclic AMP formation.

In membranes of the olfactory nerve‐glomerular layer (ON‐GL), external plexiform layer (EPL) and granule cell layer (GRL), NalBzoH elicited a concentration‐dependent stimulation of guanosine‐5′‐O‐(3‐[35S]‐thio)triphosphate ([35S]GTPγS) binding with pEC50 values ranging from 7.36 to 7.86, whereas the κ1‐opioid receptor agonists (−)‐U‐50,488 and U‐69,593 were inactive.

In membranes of GRL, but not ON‐GL and EPL, NalBzoH stimulated basal adenylyl cyclase activity by 40% with a pEC50 of 8.14, and significantly potentiated the net enzyme stimulation elicited by corticotropin‐releasing hormone and pituitary adenylate cyclase‐activating peptide 38. Pertussis toxin prevented the NalBzoH stimulations of [35S]GTPγS binding and adenylyl cyclase activity.

In membranes of EPL and GRL, but not ON‐GL, NalBzoH elicited a concentration‐dependent inhibition of forskolin‐stimulated adenylyl cyclase activity with pEC50 values of 8.07 and 8.08, respectively.

At concentrations that completely blocked the actions of nociceptin/orphanin FQ (N/OFQ), the ORL1 receptor antagonists CompB and [Nphe1]N/OFQ(1–13)NH2 failed to antagonize either the stimulatory or the inhibitory effect of NalBzoH on cyclic AMP formation. Similarly, the κ1‐opioid receptor antagonist nor‐binaltorphimine counteracted the NalBzoH effects with relatively low potencies (pKi values=7.67–8.09).

Conversely, the selective δ‐opioid receptor antagonist TIPP (pKi=9.10) and the selective μ‐opioid receptor antagonist CTAP (pKi=8.27) reduced the inhibitory effect of NalBzoH by 70 and 30%, respectively. Moreover, TIPP and CTAP potently inhibited the NalBzoH stimulation of cyclic AMP, each antagonist maximally causing 50% blockade of the agonist response.

These data demonstrate that in the olfactory bulb NalBzoH activates receptor signalling by acting through δ‐ and μ‐opioid receptors and independently of ORL1 and κ1‐opioid receptors.

British Journal of Pharmacology (2004) 143, 638–648. doi:10.1038/sj.bjp.0705951
Comparison of the antinociceptive activity of two new NO‐releasing derivatives of the NSAID S‐ketoprofen in rats
Authors: Gaitan Gema , Ahuir F Javier , Soldato Piero Del , Herrero Juan F
Published: October 2004

Nonsteroidal anti‐inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) enzymes inducing analgesic, anti‐inflammatory and antipyretic actions. They are not devoid of severe side effects and so, the search for new compounds with similar or higher effectiveness and a lower incidence of undesired actions is important. Nitric oxide (NO)‐releasing NSAIDs resulted from this search.

We have compared the antinociceptive effectiveness of cumulative doses of two new NO‐releasing derivatives of S‐ketoprofen, HCT‐2037 and HCT‐2040, using the recording of spinal cord nociceptive reflexes in anesthetized and awake rats and after intravenous and oral administration.

S‐ketoprofen and HCT‐2040 were equieffective in reducing responses to noxious mechanical stimulation after i.v. administration in anesthetized animals (ID50s: 1.3±0.1 and 1.6±0.2 μmol kg−1 respectively), but did not modify wind‐up. HCT‐2037 was two‐fold more potent (ID50 of 0.75±0.1 μmol kg−1) in responses to mechanical stimuli and very effective in reducing wind‐up (63±17% of control; P<0.01; MED: 0.4 μmol kg−1), indicating a greater activity than the parent compound.

In awake animals with inflammation, HCT‐2037 p.o. fully inhibited mechanical allodynia, 91±12% reduction, and hyperalgesia, 94±8% reduction. Equivalent doses of S‐ketoprofen only partially reduced either allodynia (50±11%) or hyperalgesia (40±4%). The effect on responses to noxious thermal stimulation was similar for the two compounds.

We conclude that the molecular changes made in the structure of S‐ketoprofen including an NO moiety in its structure, improve the antinociceptive profile of the compound opening new perspectives in a safer use of NSAIDs as analgesic drugs.

British Journal of Pharmacology (2004) 143, 533–540. doi:10.1038/sj.bjp.0705958
Acute wake‐promoting actions of JNJ‐5207852, a novel, diamine‐based H3 antagonist
Authors: Barbier A J , Berridge C , Dugovic C , Laposky A D , Wilson S J , Boggs J , Aluisio L , Lord B , Mazur C , Pudiak C M , Langlois X , Xiao W , Apodaca R , Carruthers N I , Lovenberg T W
Published: October 2004

1‐[4‐(3‐piperidin‐1‐yl‐propoxy)‐benzyl]‐piperidine (JNJ‐5207852) is a novel, non‐imidazole histamine H3 receptor antagonist, with high affinity at the rat (pKi=8.9) and human (pKi=9.24) H3 receptor. JNJ‐5207852 is selective for the H3 receptor, with negligible binding to other receptors, transporters and ion channels at 1 μM.

JNJ‐5207852 readily penetrates the brain tissue after subcutaneous (s.c.) administration, as determined by ex vivo autoradiography (ED50 of 0.13 mg kg−1 in mice). In vitro autoradiography with 3H‐JNJ‐5207852 in mouse brain slices shows a binding pattern identical to that of 3H‐R‐α‐methylhistamine, with high specific binding in the cortex, striatum and hypothalamus. No specific binding of 3H‐JNJ‐5207852 was observed in brains of H3 receptor knockout mice.

In mice and rats, JNJ‐5207852 (1–10 mg kg−1 s.c.) increases time spent awake and decreases REM sleep and slow‐wave sleep, but fails to have an effect on wakefulness or sleep in H3 receptor knockout mice. No rebound hypersomnolence, as measured by slow‐wave delta power, is observed. The wake‐promoting effects of this H3 receptor antagonist are not associated with hypermotility.

A 4‐week daily treatment of mice with JNJ‐5207852 (10 mg kg−1 i.p.) did not lead to a change in body weight, possibly due to the compound being a neutral antagonist at the H3 receptor.

JNJ‐5207852 is extensively absorbed after oral administration and reaches high brain levels.

The data indicate that JNJ‐5207852 is a novel, potent and selective H3 antagonist with good in vitro and in vivo efficacy, and confirm the wake‐promoting effects of H3 receptor antagonists.

British Journal of Pharmacology (2004) 143, 649–661. doi:10.1038/sj.bjp.0705964
Impairment of the low‐affinity state β1‐adrenoceptor‐induced relaxation in spontaneously hypertensive rats
Authors: Mallem Mohamed Yassine , Toumaniantz Gilles , Serpillon Sabrina , Gautier Freddy , Gogny Marc , Desfontis Jean‐Claude , Gauthier Chantal
Published: October 2004

In hypertension, a decrease of the vascular β‐adrenergic relaxation has been described. However, the specific involvement of each β‐adrenoceptor (β‐AR) subtype, in particular the low‐affinity state of β1‐AR, has not yet been evaluated. We investigated whether the low‐affinity state of β1‐AR‐induced relaxation was impaired in Spontaneously Hypertensive Rats (SHR).

The relaxant responses to CGP 12177 and cyanopindolol, low‐affinity state β1‐AR agonists (with β1‐/β2‐AR antagonistic and partial β3‐AR agonistic properties) were evaluated on thoracic aortic rings isolated from 12‐weeks‐old Wistar Kyoto rats (WKY) and SHR.

In WKY, CGP 12177 and cyanopindolol produced an endothelium and nitric oxide (NO)‐independent relaxation. CGP 12177‐induced endothelium‐independent relaxation was not modified either by β1‐, β2‐AR (nadolol) or β3‐AR (L‐748337 or SR 59230A) antagonists but was significantly reduced by high concentrations of CGP 20712A (P<0.05). This relaxation was also reduced by adenylyl cyclase inhibitors, SQ 22536 or MDL 12330A.

In SHR, CGP 12177 produced mainly an endothelium and NO‐dependent relaxation. This effect was not modified by nadolol, but was strongly reduced by β3‐AR blockade. Endothelium‐independent relaxation to CGP 12177 was not altered by adenylyl cyclase inhibition, but was amplified in preparations from pertussis toxin‐pretreated SHR.

The immunohistochemical analysis revealed an upregulation of β3‐AR in the endothelial layer of SHR aorta, whereas the β3‐AR‐induced relaxation was not modified.

In conclusion, we demonstrated an impaired low‐affinity state of the β1‐AR‐induced relaxation and an upregulation of the β3‐AR in hypertension. Some clinical implications of those findings are discussed.

British Journal of Pharmacology (2004) 143, 599–605. doi:10.1038/sj.bjp.0705990
Do low‐affinity states of β‐adrenoceptors have roles in physiology and medicine?
Authors: Arch Jonathan R S
Published: October 2004

The pharmacology once ascribed to the ‘β4‐adrenoceptor’ is now believed to be that of a low‐affinity state of the β1‐adrenoceptor. The β2‐adrenoceptor may also have a low‐affinity state or site, while the β3‐adrenoceptor – the original low‐affinity β‐adrenoceptor – can display more than one pharmacology. In this issue, Mallem et al. show that CGP‐12177 relaxes thoracic aorta rings from normal rats by stimulating vascular smooth muscle low‐affinity β1‐adrenoceptors, apparently linked in part to Gi protein. By contrast, in rings from hypertensive rats, CGP‐12177 acts mainly via endothelial β3‐adrenoceptors. This work raises the possibility that low‐affinity states of β‐adrenoceptors have physiological roles, and suggests that they might be drug targets.

British Journal of Pharmacology (2004) 143, 517–518. doi:10.1038/sj.bjp.0705991