bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycopolymeric inhibitors of β‐glucuronidase. III. Configurational effects of hydroxy groups in pendant glyco‐units in polymers upon inhibition of β‐glucuronidase
Authors: Hashimoto Kazuhiko , Saito Hiroshi , Ohsawa Ryo
Published: July 2006

Two kinds of new glycopolymers, (P(VB‐1‐GlcaH‐co‐AAm), 9) and (P(VB‐1‐Glco‐co‐AAm), 10), were synthesized through the radical copolymerization of styrene derivatives bearing pendant D‐glucaric and D‐gluconic moieties, N‐(p‐vinylbenzyl)‐1‐D‐glucaramide (VB‐1‐GlcaH, 7), and N‐(p‐vinylbenzyl)‐D‐gluconamide (VB‐1‐Glco, 8), with acrylamide (AAm). Glycopolymer 9 bearing the pendant glucaric moiety at the first position inhibited the hydrolysis of a model compound for xenobiotics‐β‐glucuronide conjugates, p‐nitrophenyl β‐D‐glucuronide, uncompetitively, in contrast to the competitive inhibition in the presence of the corresponding isomeric glycopolymer bearing the pendant D‐glucaric unit at the sixth position (P(VB‐6‐GlcaH‐co‐AAm), 3) reported in our previous article. On the other hand, another copolymer 10 bearing the gluconic moiety was found not to inhibit the hydrolysis as well as the corresponding copolymer bearing pendant gulonic unit (P(VB‐6‐Glco‐co‐AAm), 4). These results indicate that the hydrolysis is influenced not only by existence of pendant carboxyl units but also by the direction on the linkage of the glyco‐units to the polymer frame. Therefore the configurational position of hydroxy groups in pendant glyco‐units in macromolecular inhibitors may be essential for the interaction with β‐glucuronidase. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4895–4903, 2006
First synthesis of the bismole‐containing conjugated polymer
Authors: Morisaki Yasuhiro , Ohashi Keita , Na Hai‐Sub , Chujo Yoshiki
Published: July 2006

We successfully synthesized the first conjugated polymer containing a bismuth atom in the conjugated main chain by incorporating a bismuth atom into the cyclopentadiene framework (bismole), which was constructed by a polymer reaction. A synthetic procedure and characterization of the obtained polymers were discussed. This bismole‐containing conjugated polymer exhibited moderate bluish green photoluminescence in solution. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4857–4863, 2006
Library synthesis and characterization of 3‐aminopropyl‐terminated poly(dimethylsiloxane)s and poly(ϵ‐caprolactone)‐b‐poly(dimethylsiloxane)s
Authors: Ekin Abdullah , Webster Dean C.
Published: July 2006

Libraries of 3‐aminopropyl‐terminated poly(dimethylsiloxane) (APT–PDMS) and poly(ϵ‐caprolactone)–poly(dimethylsiloxane)–poly(ϵ‐caprolactone) (PCL—PDMS–PCL) triblock copolymers were synthesized. Preliminary experiments were carried out to select an appropriate catalyst and route for the poly(dimethylsiloxane) synthesis, and trial experiments were conducted to verify the successful synthesis of the intended polymer compositions. Then, a series of APT–PDMS oligomers were synthesized with an automated combinatorial high‐throughput synthesis system to cover a molecular weight range of 2500–50,000 g/mol. Trial PCL—PDMS–PCL triblock copolymers were synthesized with the automated reactor system and characterized in detail with rapid gel permeation chromatography, high‐throughput Fourier transform infrared, nuclear magnetic resonance, and differential scanning calorimetry. Finally, two library synthesis experiments were carried out in which the lengths of both the poly(dimethylsiloxane) and poly(ϵ‐caprolactone) blocks in the PCL—PDMS–PCL triblock copolymers were varied. The results obtained from these experiments demonstrated that it was possible to synthesize libraries of well‐defined APT–PDMS oligomers and PCL—PDMS–PCL triblock copolymers with an automated high‐throughput system. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4880–4894, 2006
Evaluation of daily home spirometry for school children with asthma: New insights
Authors: Thompson Rohan , Delfino Ralph J. , Tjoa Thomas , Nussbaum Eliezer , Cooper Dan
Published: July 2006

Home spirometers are useful for monitoring asthma therapy and for research, but the validity of maneuvers in children is in question. We evaluated the quality of PEF, FEV1, and FVC data obtained from 67 children with persistent asthma who self‐administered spirometry at home using the hand‐held ndd EasyOne Frontline Spirometer with full expiratory curve data, electronic measurements of maneuver quality, and on‐screen incentives. Half were studied in 2003 in one region, and half in 2004 in another region of Southern California. Subjects were followed at home weekly over 2 months and daily over 10 consecutive days. We retained completed spirometry sessions (9,916) consisting of three of six best maneuvers in the morning, afternoon, and evening. Percent compliance, software assessed repeatability and acceptability modified from American Thoracic Society criteria, and visually assessed quality of maneuvers, were compared across daily and weekly follow‐up, study regions, and subject characteristics. Compliance was higher for daily (>90%) than for weekly follow‐up (>84%), but not significantly different, and was consistent across subject characteristics. The number with two reproducible and acceptable maneuvers was significantly lower in the first than second region for daily (70 vs. 90%) and weekly follow‐up (66 vs. 87%). Of 22,926 software accepted maneuvers, 1,944 (8.5%) were visually rejected (variable effort, cough, glottic closure). Maneuver quality was significantly lower for subjects age 9–12 versus 13–18 years, for subjects not taking anti‐inflammatory medications, and for subjects with <80% predicted FEV1. Longitudinal data collection is possible in children with asthma by employing repeated home training and follow‐up, and using spirometers with built in quality assurance and incentive software. Region, age, and multiple indicators of persistent asthma, predict ability to perform reliable and accurate lung function maneuvers. Pediatr Pulmonol. © 2006 Wiley‐Liss, Inc.
The therapy of pre‐school wheeze: Appropriate and fair?
Authors: Chauliac E.S. , Silverman M. , Zwahlen M. , Strippoli M‐P F. , Brooke A.M. , Kuehni and C.E.
Published: July 2006

The current study aimed to assess prevalence and distribution of use of asthma medication for wheeze in pre‐school children in the community. We sent a postal questionnaire to the parents of a random population‐based sample of 4,277 UK children aged 1–5 years; 3,410 participated (children of south Asian decent were deliberately over‐represented). During the previous 12 months, 18% of the children were reported to have received bronchodilators, 8% inhaled corticosteroids (ICS) and 3% oral corticosteroids. Among current wheezers these proportions were 55%, 25%, and 12%, respectively. Use of ICS increased with reported severity of wheeze, but did not reach 60% even in the most severe category. In contrast, 42% of children receiving ICS reported no or very infrequent recent wheeze. Among children with the episodic viral wheeze phenotype, 17% received ICS compared with 40% among multiple‐trigger wheezers. Use of ICS by current wheezers was less common in children of South Asian ethnicity and in girls. Although a high proportion of pre‐school children in the community used asthma inhalers, treatment seemed to be insufficiently adjusted to severity or phenotype of wheeze, with relative under‐treatment of severe wheeze with ICS, especially in girls and South Asian children, but apparent over‐treatment of mild and episodic viral wheeze and chronic cough. Pediatr Pulmonol. © 2006 Wiley‐Liss, Inc.
Degradation of anilinopyrimidine fungicides photoinduced by iron(III)–polycarboxylate complexes
Authors: Anfossi Laura , Sales Paolo , Vanni Adriano
Published: July 2006

The photoinduced degradation of three anilinopyrimidine fungicides (cyprodinil, pyrimethanil and mepanipyrim) by Fe(III)–polycarboxylate complexes in aqueous solution was investigated. A photochemical redox reaction of Fe(III) complexes of oxalate and citrate occurs during irradiation (simulating sunlight) and is an important source of Fe(II) and a series of oxidants such as H2O2 and O radicals. The mechanism involves the formation of polycarboxylate radicals and/or carbon‐centred radicals derived from decarboxylation, whereas the contribution of Fe(OH)2+ to O radical formation is negligible. The attack of O radicals on the fungicide molecules produces numerous photodegradation products, which were identified by means of LC‐ES‐MS and turned out to be mono‐ or dihydroxylated derivatives of the active ingredients, except for 2‐amino‐4,6‐dimethylpyrimidine, which is only formed by pyrimethanil. The half‐lives of the active ingredients, when submitted to irradiation in the presence of iron(III)–polycarboxylate complexes, were estimated to vary between 28 and 79 min (photodegradation rates in the same conditions: mepanipyrim > cyprodinil > pyrimethanil), and photodegradation is slower in citrate than in oxalate solutions. Photoproducts and their kinetics of formation are very similar for the three fungicides. The OH substitution involves the aromatic and the heterocyclic ring and the nitrogen bridge between the two rings, except for mepanipyrim when the hydroxylation also involves the propynylic side chain. Copyright © 2006 Society of Chemical Industry
Azadirachtin‐A and tetrahydroazadirachtin‐A concentrates: preparation, LC‐MS characterization and insect antifeedant/IGR activity against Helicoverpa armigera (Hübner)
Authors: Sharma Vandana , Walia Suresh , Dhingra Swaran , Kumar Jitendra , Parmar Balraj S
Published: July 2006

A 60% azadirachtin‐A concentrate has been obtained through repeated precipitation with hexane from a methanolic solution of a 20% concentrate. Azadirachtin‐A (90%) has been obtained by medium‐pressure liquid chromatography of the 60% concentrate with an RP‐18 column and a methanol + water (1 + 1 by volume) solvent system. Catalytic hydrogenation of the 60 and 90% azadirachtin concentrates yielded the corresponding tetrahydroazadirachtin concentrates. Dihydroazadirachtin and tetrahydroazadirachtin formed during the first 5 h of hydrogenation were identified by LC‐ESI‐MS on the basis of their unique mass fragmentation pattern. The efficacy of tetrahydroazadirachtin concentrates in inhibiting the feeding and growth of Helicoverpa armigera (Hübner) larvae has been compared with that of azadirachtin concentrates. They were in general more active and deterred larvae from feeding at all concentrations. Tetrahydroazadirachtin‐A (90%) and azadirachtin‐A (90%) with respective IC50 values of 280 and 390 mg L−1 were effective as insect growth regulators, while tetrahydroazadirachtin‐A (90%) displayed higher antifeedant activity (AI50 14 mg L−1) against the test insect. Copyright © 2006 Society of Chemical Industry
Insecticidal, antifeedant and oviposition deterrent effects of the essential oil and individual compounds from leaves of Chloroxylon swietenia DC.
Authors: Kiran S Ravi , Reddy A Shiva , Devi P Sita , Reddy K Janardhan
Published: July 2006

Essential oil from the leaves of Chloroxylon swietenia DC. was obtained by hydrodistillation and cold extraction, and the chemical composition was determined by gas chromatography and gas chromatography‐mass spectrometry. The major identified components were limonene, geijerene, pregeijerene, germacrene D and trans‐β‐ocimene. Laboratory bioassays of the essential oil and four constituents of essential oil isolates were evaluated for insecticidal, antifeedant and oviposition deterrent effects on tobacco cutworm, Spodoptera litura (F.). Toxicity was determined by topical application of the isolates at varying concentrations. Pure oil, geijerene and pregeijerene were found to be more toxic, with LD50 values of 28.6, 35.4 and 40.7 µg per larva respectively. Maximum feeding deterrence was noted for geijerene and pregeijerene, with DC50 values of 82.5 and 95.1 µg cm−2 respectively. Furthermore, pure oil, geijerene and pregeijerene displayed oviposition deterrence, even at low concentrations. These results indicate that these natural products may lead to useful, biodegradable, environmentally safe insect control agents. Copyright © 2006 Society of Chemical Industry
Routines, roles, and responsibilities for aligning scientific and classroom practices
Authors: Ford Michael J. , Wargo Brian M.
Published: July 2006

Reform efforts in science education have focused on engaging students in authentic scientific practices. For these efforts to succeed, detailed articulations of scientific practice need to be linked to understandings of classroom practice. Here we characterize engagement in practice generally in terms of “3Rs”: routines, roles, and responsibilities. We argue that there is a misalignment between the 3Rs of scientific practice and the practices common in classrooms, and that this misalignment poses a considerable obstacle for beginning teachers who attempt to implement reform pedagogy. As part of a secondary methods course, 16 preservice teachers (PSTs) participated in two exemplar activities designed to engage them in scientific practices. The PST performances suggest that at least initially, they did not consider authentic scientific practices appropriate for classroom activities, implying a pedagogical repertoire dominated by the 3Rs of traditional classrooms. PST performances, however, evidenced a shift in the 3Rs from those common in classrooms to those required by these activities, suggesting that their visions for classrooms are malleable and underlining the importance of aligning the 3Rs of scientific and classroom practices during teacher preparation. © 2006 Wiley Periodicals, Inc. Sci Ed 91:133–157, 2007
Molecular characterization of the Tim9 homologue from the methylotrophic yeast Pichia methanolica
Authors: Matsufuji Yoshimi , Nakagawa Tomoyuki , Ito Takashi , Fujimura Shuki , Chikui Mika , Miyaji Tatsuro , Tomizuka Noboru
Published: July 2006

In this paper we describe molecular characterization of the TIM9 gene encoding the essential mitochondrial inner‐membrane protein in the methylotrophic yeast Pichia methanolica. PmTIM9 contains two exons corresponding to a gene product of 89 amino acid residues and a 140 bp intron. The deduced amino acid sequence exhibited high identity to those of other yeast Tim9ps, and possessed two CX3C motifs that contained two cysteine residues conserved among small Tim family proteins. Moreover, PmTIM9 had the ability to partially suppress the temperature sensitivity of Saccharomyces cerevisiae strain tim9‐3, suggesting that PmTIM9 is a functional homologue of the ScTIM9 gene. Copyright © 2006 John Wiley & Sons, Ltd.
Analysis of expressed sequence tags from the anamorphic basidiomycetous yeast, Pseudozyma antarctica, which produces glycolipid biosurfactants, mannosylerythritol lipids
Authors: Morita Tomotake , Konishi Masaaki , Fukuoka Tokuma , Imura Tomohiro , Kitamoto Dai
Published: July 2006

Pseudozyma antarctica T‐34 secretes a large amount of biosurfactants (BS), mannosylerythritol lipids (MEL), from different carbon sources such as hydrocarbons and vegetable oils. The detailed biosynthetic pathway of MEL remained unknown due to lack of genetic information on the anamorphic basidiomycetous yeasts, including the genus Pseudozyma. Here, in order to obtain genetic information on P. antarctica T‐34, we constructed a cDNA library from yeast cells producing MEL from soybean oil and identified the genes expressed through the creation of an expressed sequence tags (EST) library. We generated 398 ESTs, assembled into 146 contiguous sequences. Based upon a BLAST search similarity cut‐off of E≤10−5, 21.4% of all contigs were orphan, while 78.6% showed similarity to sequences in the protein database; 60.3% of all contiguous sequences shared significant identities to hypothetical protein of Ustilago maydis, which is a smut fungus and BS producer. Based on the gene expression study using real‐time reverse transcriptase‐PCR, the predicted genes, such as mannosyltranferase and acyltransferase, were demonstrated to be highly involved in MEL biosynthesis in soybean oil‐grown cells. Copyright © 2006 John Wiley & Sons, Ltd.
Various cytosine/adenine permease homologues are involved in the toxicity of 5‐fluorocytosine in Saccharomyces cerevisiae
Authors: Paluszynski John P. , Klassen Roland , Rohe Matthias , Meinhardt Friedhelm
Published: July 2006

5‐Fluorocytosine (5‐FC), a medically applied antifungal agent (Ancotil®), is also active against the model organism Saccharomyces cerevisiae. 5‐FC uptake in S. cerevisiae was considered to be mediated by the FCY2‐encoded cytosine/adenine permease. By applying a highly sensitive assay, a low‐level but dose‐dependent toxicity of 5‐FC in fcy2 mutants was detected, whereas cells deficient in the cytosine deaminase (encoded by FCY1), which is essential for intracellular conversion of 5‐FC to 5‐fluorouracil, display strong dose‐independent resistance. Thus, an alternative, Fcy2‐independent access pathway for 5‐FC exists in S. cerevisiae. A genome‐wide search for cytosine permease homologues identified two uncharacterized candidate genes, designated FCY21 and FCY22, both of which exhibit highest similarity to FCY2. Disruption of either FCY21 or FCY22 resulted in strains displaying low‐level resistance, indicating the functional involvement of both gene products in 5‐FC toxicity. When mutations in FCY21 or FCY22 were combined with the FCY2 disruption, both double mutants displayed stronger resistance when compared to the FCY2 mutant alone. Disruptions in all three permease genes consequently conferred the highest degree of resistance, not only towards 5‐FC but also to the toxic adenine analogon 8‐azaadenine. As residual 5‐FC sensitivity was, however, even detectable in the fcy2 fcy21 fcy22 mutant, we analysed the relevance of other FCY2 homologues, i.e. TPN1, FUR4, DAL4, FUI1 and yOR071c, for 5‐FC toxicity. Among these, Tpn1, Fur4 and the one encoded by yOR071c were found to contribute significantly to 5‐FC toxicity, thus revealing alternative entry routes for 5‐FC via other cytosine/adenine permease homologues. Copyright © 2006 John Wiley & Sons, Ltd.
Surgical Treatment of Metastatic Tumors to the Pancreas: A Single Center Experience and Review of the Literature
Authors: Crippa Stefano , Angelini Carlo , Mussi Chiara , Bonardi Claudia , Romano Fabrizio , Sartori Paola , Uggeri Franco , Bovo Giorgio
Published: July 2006

Background

Unlike primary pancreatic carcinoma, metastases to the pancreas are rare, and their resection may be performed as palliative treatment. The aim of this study was to review our experience with the operative management of pancreatic metastases.

Materials and Methods

Between January 1994 and December 2004 13 patients (nine women and four men; median age: 59 years; range: 36–79 years) were admitted to our institution with metastatic lesion to the pancreas. The clinical features of the treatment and results were examined.

Results

Primary tumors were renal cell carcinoma (n = 5), lobular carcinoma of the breast (n = 3), endometrioid carcinoma of the ovary (n = 1), colonic adenocarcinoma (n = 1), jejunal leiomyosarcoma (n = 1), melanoma (n = 1), and non‐small‐cell lung cancer (n = 1). The median interval between primary tumor and pancreatic metastases was 36 months (range: 5–192 months). Six patients (46%) were asymptomatic, while the other seven patients presented with jaundice, pain, and duodenal obstruction. Two patients with extrapancreatic disease underwent palliative surgery, and the remaining 11 patients underwent operative procedures that included seven pancreaticoduodenectomy and four distal pancreatectomies with splenectomy. Postoperative mortality was nil, and the morbidity rate was 30%. The two patients who underwent palliative surgery died after 7 and 9 months, respectively. The median survival of the resected patients was 26 months (range: 13–95 months). Five patients died of disease, eight are alive at the time of this report.

Conclusion

A trend towards improved survival, even if not statistically significant, was observed in the renal carcinoma patients reported here. Surgical resection can be performed safely in selected patients with isolated metastases to the pancreas, achieving long‐term survival as well as good palliation.
Granulomatous Lobular Mastitis: A Complex Diagnostic and Therapeutic Problem
Authors: Akcan Alper , Akyıldız Hızır , Deneme Mehmet Ali , Akgun Hulya , Arıtas Yucel
Published: July 2006

Background

Granulomatous lobular mastitis is a rare chronic inflammatory disease of the breast. Clinical and radiological features may mimic breast carcinoma. Since this entity was first described, several clinical and pathologic features of the disease have been reported, but diagnostic features and treatment alternatives are still unclear. The purpose of this study is to evaluate diagnostic difficulties and discuss the outcome of surgical treatment in a series of 21 patients with granulomatous lobular mastitis.

Methods

A retrospective review of 21 patients with histologically confirmed granulomatous lobular mastitis treated in our center between January 1995 and May 2005 was analyzed to identify issues in the diagnosis and treatment of this rare condition.

Results

The most common presenting symptoms were a mass in the breast and pain. Four patients had no significant mammographic findings (MMG), but on ultrasound (US), 2 had irregular hypoechoic mass, and 2 hypoechoic nodular structures had abnormalities—one parenchymal distortion and 1 mass formation in 2 of these 4 patients’ magnetic resonance imaging (MRI). In recurrent cases, limited excision under local anesthesia was performed, as the clinical examination suggested carcinoma.

Conclusions

Although some findings on MMG and US are suggestive of benign breast disease, these modalities do not rule out malignancy. MRI may be helpful in patients who do not have significant pathology at MMG or US. Fine‐needle aspiration cytology may be useful in some cases but diagnosis is potentially difficult because of its cytologic characteristics. Wide excision, particularly under general anesthesia, can be therapeutic as well as useful in providing an exact diagnosis.
Endovascular Techniques for the Treatment of Ruptured Abdominal Aortic Aneurysms: 7‐year Intention‐to‐treat Results
Authors: Dalainas Ilias , Nano Giovanni , Bianchi Paolo , Stegher Silvia , Casana Renato , Malacrida Giovanni , Tealdi Domenico G.
Published: July 2006

Objectives

The purpose of this single‐institution study was to describe our 7‐year intention‐to‐treat results, obtained with the use of endovascular techniques for the treatment of ruptured abdominal aortic aneurysms (rAAA).

Patients and Methods

From October 1998 until March 2005, a total of 28 patients were admitted or transferred to our department with an rAAA. They were all treated according to a management protocol of intention‐to‐treat with endovascular techniques. Twenty of the patients received endovascular treatment and the remaining 8 underwent an open surgery procedure.

Results

The mortality rate of the endovascularly treated patients was 40% (8 in 20), whereas of the 8 surgical patients 3 survived (mortality = 62.5%). The overall mortality rate of the 28 patients admitted with an rAAA was 46.4% (13 of 28 patients).

Conclusions

In our experience the intension‐to‐treat protocol for rAAA offered acceptable results in terms of mortality rates. Multi‐center studies are necessary to establish the role of endovascular treatment in patients with rAAA.
Acute Intraperitoneal Rupture of Hydatid Cysts
Authors: Derici Hayrullah , Tansug Tugrul , Reyhan Enver , Bozdag Ali Dogan , Nazli Okay
Published: July 2006

Background

Rupture into the abdominal cavity is a rare but serious complication of hydatid disease. The cysts may be ruptured after a trauma, or spontaneously as a result of increased intracystic pressure. Rupture of the hydatid cyst requires emergency surgical intervention.

Methods

Seventeen patients received surgical treatment for intraperitoneal rupture of the cysts over a period of 18 years. Age, gender, time to surgery from the onset of the symptoms, laboratory findings, diagnostic procedures, surgical treatment modalities, in‐hospital stay, morbidity, mortality and recurrence were evaluated retrospectively.

Results

Five cases (29.4%) had a history of blunt abdominal trauma. Ultrasonography scans revealed intra‐abdominal fluid in all cases. Intraperitoneal multiple cysts with heterogeneous cavity or cystic structures in the liver were shown in 14 cases. Computed tomography and magnetic resonance imaging showed multiple cystic lesions in the liver and peritoneum with intra‐abdominal free fluid. Procedures to fill the cystic cavities were applied after removal of the intraperitoneal fluid. Four patients (23.5%) died in the early postoperative period. A total of nine morbidities developed in six patients (35.3%). Median hospital stay was 18 days and median follow‐up was 78 months. Intra‐abdominal recurrence occurred in one case (7.7%).

Conclusions

Rupture of hydatid cysts into the peritoneal cavity, although rare, presents a challenge for surgeons. This pathology should be included in the differential diagnosis of acute abdomen in endemic areas. Computed tomography scan, in addition to clinical presentation, is essential for diagnosis. Emergency surgery is the main treatment for acute ruptured hydatid cysts. The morbidity and mortality rates of surgical interventions for ruptured hydatid cysts are higher than the rates for elective uncomplicated cases.
The Journal of the Future Is Here Today
Authors: Hunter John G.
Published: July 2006

Scientific publishing has undergone a complete transformation in the last two decades. While the process of peer review may differ little from what it was during the last 50 years, electronic indexing, electronic access, and now electronic submission of scientific manuscripts has transformed the surgical journal in the last decade. In fact, the editorial office of the journal has contracted to a workstation, a fax machine, a telephone, and a storage locker for the aging paper records.
Annual changes in the proportions of wild and hatchery Atlantic salmon (Salmo salar) caught in the Baltic Sea
Authors: Koljonen Marja-Liisa
Published: July 2006

DNA-level information from an eight-loci microsatellite baseline database of 32 Atlantic salmon (Salmo salar) stocks was used with a Bayesian estimation method to assess the stock and stock group proportions of Finnish salmon catches in the Baltic Sea area. The proportions of seven stock groups, important to fisheries management, were assessed in catch samples taken between 2000 and 2005. In the Gulf of Bothnia area, the proportion of wild fish in catches showed an increasing trend in all areas until 2003, mainly because of the decrease in total catches caused by the relatively greater mortality of hatchery-reared fish compared with wild fish. In 2004, the total number of wild fish caught had also increased, indicating an increase in the abundance of wild stocks. In catches from the Åland Sea, the proportion of wild fish increased from 44% in 2000 to 70% in 2004, while the catch during the same period increased from 4628 to 7329 fish. In the Gulf of Finland, the local Neva salmon stock, which is released by Estonia, Finland, and Russia, made the largest contribution. In the western part of the Gulf of Finland, fish originating in the Baltic Main Basin also made a substantial contribution to catches. The threatened eastern Estonian and Russian wild stocks were recorded only in the western part of the Gulf of Finland, where the proportion of wild fish increased from 9% in 2003 to 19% in 2004.
Vitamin A active metabolite, all‐trans retinoic acid, induces spinal cord sensitization. II. Effects after intrathecal administration
Authors: Alique M , Lucio F J , Herrero J F
Published: July 2006

Background and purpose:

In our previous study (see accompanying paper) we observed that all‐trans retinoic acid (ATRA) p.o. induces changes in spinal cord neuronal responses similar to those observed in inflammation‐induced sensitization. In the present study we assessed the it. effects of ATRA, and its mechanisms of action.

Experimental approach:

The effects of all drugs were studied after it. administration in nociceptive withdrawal reflexes using behavioural tests in awake male Wistar rats.

Key results:

The administration of ATRA in normal rats induced a dose‐dependent enhancement of nociceptive responses to noxious mechanical and thermal stimulation, as well as responses to innocuous stimulation. The intensity of the responses was similar to that observed in non‐treated animals after carrageenan‐induced inflammation. The effect induced by ATRA was fully prevented by the previous administration of the retinoic acid receptor (RAR) pan‐antagonist LE540 but not by the retinoid X receptor (RXR) pan‐antagonist HX531, suggesting a selective action on spinal cord RARs. The COX inhibitor dexketoprofen and the interleukin‐1 receptor antagonist IL‐1ra inhibited ATRA effect. The results indicate that COX and interleukin‐1 are involved in the effects of ATRA in the spinal cord, similar to that seen in inflammation.

Conclusions and implications:

In conclusion, ATRA induces changes in the spinal cord similar to those observed in inflammation. The sensitization‐like effect induced by ATRA was mediated by RARs and associated with a modulation of COX‐2 and interleukin‐1 activities. ATRA might be involved in the mechanisms underlying the initiation and/or maintenance of sensitization in the spinal cord.

British Journal of Pharmacology (2006) 149, 65–72. doi:10.1038/sj.bjp.0706826
Preclinical pharmacokinetics, pharmacodynamics, and activity of a humanized anti‐CD40 antibody (SGN‐40) in rodents and non‐human primates
Authors: Kelley Sean K , Gelzleichter Thomas , Xie Dong , Lee Wyne P , Darbonne Walter C , Qureshi Ferhan , Kissler Kim , Oflazoglu Ezogelin , Grewal Iqbal S
Published: July 2006

Cell‐surface expression of CD40 in B‐cell malignancies and multiple solid tumors has raised interest in its potential use as a target for antibody‐based cancer therapy. SGN‐40, a humanized monoclonal anti‐CD40 antibody, mediates antibody‐dependent cytotoxicity and inhibits B‐cell tumor growth in vitro, properties of interest for the treatment of cancers, and is currently in Phase I clinical trials for B‐cell malignancies. In this study, we determined in vivo activity and pharmacokinetics properties of SGN‐40.

Effect of SGN‐40 in xenograft model of CD40‐expressing B‐cell lymphoma in severe‐combined immune deficiency mice and its in vivo pharmacokinetics properties in normal mice, rats and cynomolgus monkeys were studied.

Treatment with SGN‐40 significantly increased the survival of mice xenografted with human B‐cell lymphoma cell line. SGN‐40 exhibited nearly 100% bioavailability in mice and it cleared faster when given at a low dose. In monkeys, clearance of SGN‐40 was also much faster at low dose, suggesting nonlinear pharmacokinetics in these species. In rats, however, SGN‐40 clearance at all tested doses was similar, suggesting that pharmacokinetics were linear in this dose range in rats. Administration of SGN‐40 to monkeys also produced marked, dose‐dependent, and persistent depletion of peripheral CD20+ B lymphocytes.

Data presented in this report suggest that SGN‐40 is active in in vivo, and based upon interspecies scaling, SGN‐40 clearance in humans is predicted to be similar to observed SGN‐40 clearance in monkeys. These data suggest that SGN‐40 has appropriate pharmacokinetic properties that support its clinical use.

British Journal of Pharmacology (2006) 148, 1116–1123. doi:10.1038/sj.bjp.0706828
Neuronal and smooth muscle receptors involved in the PACAP‐ and VIP‐induced relaxations of the pig urinary bladder neck
Authors: Hernández M , Barahona M V , Recio P , Benedito S , Martínez A C , Rivera L , García‐Sacristán A , Prieto D , Orensanz L M
Published: July 2006

Background and purpose:

As pituitary adenylate cyclase‐activating polypeptide 38 (PACAP 38)‐ and vasoactive intestinal peptide (VIP) are widely distributed in the urinary tract, the current study investigated the receptors and mechanisms involved in relaxations induced by these peptides in the pig bladder neck.

Experimental approach:

Urothelium‐denuded strips were suspended in organ baths for isometric force recordings and the relaxations to VIP and PACAP analogues were investigated.

Key results:

VIP, PACAP 38, PACAP 27 and [Ala11,22,28]‐VIP produced similar relaxations. Inhibition of neuronal voltage‐gated Ca2+channels reduced relaxations to PACAP 38 and increased those induced by VIP. Blockade of capsaicin‐sensitive primary afferents (CSPA), nitric oxide (NO)‐synthase or guanylate cyclase reduced the PACAP 38 relaxations but failed to modify the VIP responses. Inhibition of VIP/PACAP receptors and of voltage‐gated K+channels reduced PACAP 38 and VIP relaxations, which were not modified by the K+channel blockers iberiotoxin, charybdotoxin, apamin or glibenclamide. The phosphodiesterase 4 inhibitor rolipram and the adenylate cyclase activator forskolin produced potent relaxations. Blockade of protein kinase A (PKA) reduced PACAP 38‐ and VIP‐induced relaxations.

Conclusions and implications:

PACAP 38 and VIP relax the pig urinary bladder neck through muscle VPAC2receptors linked to the cAMP‐PKA pathway and involve activation of voltage‐gated K+channels. Facilitatory PAC1receptors located at CSPA and coupled to NO release, and inhibitory VPAC receptors at motor endings are also involved in the relaxations to PACAP 38 and VIP, respectively. VIP/PACAP receptor antagonists could be useful in the therapy of urinary incontinence produced by intrinsic sphincter deficiency.

British Journal of Pharmacology(2006)149, 100–109. doi:10.1038/sj.bjp.0706832
Leptin, the obesity‐associated hormone, exhibits direct cardioprotective effects
Authors: Smith C C T , Mocanu M M , Davidson S M , Wynne A M , Simpkin J C , Yellon D M
Published: July 2006

Background and purpose: Protection against ischaemia‐reperfusion (I/R) injury involves PI3K‐Akt and p44/42 MAPK activation. Leptin which regulates appetite and energy balance also promotes myocyte proliferation via PI3K‐Akt and p44/42 MAPK activation. We, therefore, hypothesized that leptin may also exhibit cardioprotective activity.

Experimental approach: The influence of leptin on I/R injury was examined in perfused hearts from C57Bl/6 J mice that underwent 35 min global ischaemia and 35 min reperfusion, infarct size being assessed by triphenyltetrazolium chloride staining. The concomitant activation of cell‐signalling pathways was investigated by Western blotting. The effect of leptin on mitochondrial permeability transition pore (MPTP) opening was studied in rat cardiomyocytes.

Key results: Leptin (10 nM) administered during reperfusion reduced infarct size significantly. Protection was blocked by either LY294002 or UO126, inhibitors of Akt and p44/42 MAPK, respectively. Western blotting confirmed that leptin stimulated p44/42 MAPK phosphorylation significantly. Akt phosphorylation was also enhanced but did not achieve statistical significance. Additionally, leptin treatment was associated with a significant increase in p38 phosphorylation. By contrast, leptin caused downregulation of phosphorylated and non‐phosphorylated STAT3, and of total AMP‐activated kinase. Cardiomyocytes responded to leptin with delayed opening of the MPTP and delayed time until contracture.

Conclusions and implications: Our data indicate for the first time that the adipocytokine, leptin, has direct cardioprotective properties which may involve the PI3‐Akt and p44/42 MAPK pathways.

British Journal of Pharmacology (2006) 149, 5–13. doi:10.1038/sj.bjp.0706834
Resveratrol inhibits insulin responses in a SirT1-independent pathway
Authors: Zhang Jiandi
Published: July 2006

Resveratrol mimics calorie restriction to extend lifespan of Caenorhabditis elegans, yeast and Drosophila, possibly through activation of Sir2 (silent information regulator 2), a NAD+-dependent histone deacetylase. In the present study, resveratrol is shown to inhibit the insulin signalling pathway in several cell lines and rat primary hepatocytes in addition to its broad-spectrum inhibition of several signalling pathways. Resveratrol effectively inhibits insulin-induced Akt and MAPK (mitogen-activated protein kinase) activation mainly through disruption of the interactions between insulin receptor substrates and its downstream binding proteins including p85 regulatory subunit of phosphoinositide 3-kinase and Grb2 (growth factor receptor-bound protein 2). The inhibitory effect of resveratrol on insulin signalling is also demonstrated at mRNA level, where resveratrol reverses insulin effects on phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, fatty acid synthase and glucokinase. In addition, RNA interference experiment shows that the inhibitory effect of resveratrol on insulin signalling pathway is not weakened in cells with reduced expression of SirT1, the mammalian counterpart of Sir2. These observations raise the possibility that resveratrol may additionally modulate lifespan through inhibition of insulin signalling pathway, independently of its activation of SirT1 histone deacetylase. Furthermore, the present study may help to explain a wide range of biological effects of resveratrol, and provides further insight into the molecular basis of calorie restriction.
NF-Y and Sp1/Sp3 are involved in the transcriptional regulation of the peptidylarginine deiminase type III gene (PADI3) in human keratinocytes
Authors: Dong Sijun , Kanno Takuya , Yamaki Ayako , Kojima Toshio , Shiraiwa Masakazu , Kawada Akira , Méchin Marie-Claire , Chavanas Stéphane , Serre Guy , Simon Michel , Takahara Hidenari
Published: July 2006

Human peptidylarginine deiminase type III gene (PADI3) encodes a crucial post-translational modification enzyme that converts protein-bound arginine residues into citrulline residues. Its expression is restricted to a few cell types, including keratinocytes in the granular layer of the epidermis and in the inner root sheath of hair follicles. In these cells, the enzyme is involved in terminal processing of intermediate filament-binding proteins such as filaggrin and trichohyalin. To study the molecular mechanisms that control the expression of PADI3 in human keratinocytes at the transcriptional level, we characterized its promoter region using human keratinocytes transfected with variously deleted fragments of the 5′-upstream region of PADI3 coupled to the luciferase gene. We found that as few as 129 bp upstream from the transcription initiation site were sufficient to direct transcription of the reporter gene. Electrophoretic mobility-shift and chromatin immunoprecipitation assays revealed that NF-Y (nuclear factor Y) and Sp1/Sp3 (specificity protein 1/3) bind to this region in vitro and in vivo. Moreover, mutation of the Sp1- or NF-Y-binding motif markedly reduced PADI3 promoter activity. Furthermore, Sp1 or NF-YA (NF-Y subunit) small interfering RNAs effectively diminished PADI3 expression in keratinocytes cultured in both low- and high-calcium medium. These data indicate that PADI3 expression is driven by Sp1/Sp3 and NF-Y binding to the promoter region.
Identification of a PDZ protein, PIST, as a binding partner for Rho effector Rhotekin: biochemical and cell-biological characterization of Rhotekin–PIST interaction
Authors: Ito Hidenori , Iwamoto Ikuko , Morishita Rika , Nozawa Yoshinori , Asano Tomiko , Nagata Koh-ichi
Published: July 2006

Among various effector proteins for the small GTPase Rho, the function(s) of Rhotekin is (are) almost unknown. We have identified PIST [PDZ (PSD-95, Discs-large and ZO-1) domain protein interacting specifically with TC10 (a Rho-family small GTPase)] as a binding partner for Rhotekin, using yeast two-hybrid screening. Rhotekin was found to associate with PIST in vitro and in both polarized and non-polarized MDCK (Madin–Darby canine kidney) cells. The C-terminal SPV (Ser-Pro-Val) motif of Rhotekin exhibited binding to the PDZ domain of PIST. The binding was markedly inhibited by an activated version of Rho and partially by that of Rac or Cdc42 in COS7 cells. In contrast, TC10 had no effects on the binding. Immunofluorescence analyses revealed the co-localization of PIST and Rhotekin at the Golgi apparatus in non-polarized fibroblast-like MDCK cells and AJs (adherens junctions) in the fully polarized cells. PIST and Rhotekin are recruited from the cytosol to AJs as the cell becomes polarized. Expression of constitutively active Rho or prevention of Rhotekin–PIST interaction induced diffuse cytoplasmic distribution of Rhotekin in polarized MDCK cells. These results suggest that there is (1) Rho-dependent regulation of Rhotekin-PIST interaction, (2) involvement of PIST in the recruitment of Rhotekin to AJs and (3) a possible role(s) for these two proteins in cell-polarity development and/or maintenance.
Biochemical characterization of detergent-resistant membranes: a systematic approach
Authors: Babiychuk Eduard B. , Draeger Annette
Published: July 2006

Lateral segregation of cholesterol- and sphingomyelin-rich rafts and glycerophospholipid-containing non-raft microdomains has been proposed to play a role in a variety of biological processes. The most compelling evidence for membrane segregation is based on the observation that extraction with non-ionic detergents leads to solubilization of a subset of membrane components only. However, one decade later, a large body of inconsistent detergent-extraction data is threatening the very concept of membrane segregation. We have assessed the validity of the existing paradigms and we show the following. (i) The localization of a membrane component within a particular fraction of a sucrose gradient cannot be taken as a yardstick for its solubility: a variable localization of the DRMs (detergent-resistant membranes) in sucrose gradients is the result of complex associations between the membrane skeleton and the lipid bilayer. (ii) DRMs of variable composition can be generated by using a single detergent, the increasing concentration of which gradually extracts one protein/lipid after another. Therefore any extraction pattern obtained by a single concentration experiment is bound to be ‘investigator-specific’. It follows that comparison of DRMs obtained by different detergents in a single concentration experiment is prone to misinterpretations. (iii) Depletion of cholesterol has a graded effect on membrane solubility. (iv) Differences in detergent solubility of the members of the annexin protein family arise from their association with chemically different membrane compartments; however, these cannot be attributed to the ‘brick-like’ raft-building blocks of fixed size and chemical composition. Our findings demonstrate a need for critical re-evaluation of the accumulated detergent-extraction data.
Role of pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) in glucose homoeostasis during starvation
Authors: Jeoung Nam Ho , Wu Pengfei , Joshi Mandar A. , Jaskiewicz Jerzy , Bock Cheryl B. , Depaoli-Roach Anna A. , Harris Robert A.
Published: July 2006

The PDC (pyruvate dehydrogenase complex) is strongly inhibited by phosphorylation during starvation to conserve substrates for gluconeogenesis. The role of PDHK4 (pyruvate dehydrogenase kinase isoenzyme 4) in regulation of PDC by this mechanism was investigated with PDHK4−/− mice (homozygous PDHK4 knockout mice). Starvation lowers blood glucose more in mice lacking PDHK4 than in wild-type mice. The activity state of PDC (percentage dephosphorylated and active) is greater in kidney, gastrocnemius muscle, diaphragm and heart but not in the liver of starved PDHK4−/− mice. Intermediates of the gluconeogenic pathway are lower in concentration in the liver of starved PDHK4−/− mice, consistent with a lower rate of gluconeogenesis due to a substrate supply limitation. The concentration of gluconeogenic substrates is lower in the blood of starved PDHK4−/− mice, consistent with reduced formation in peripheral tissues. Isolated diaphragms from starved PDHK4−/− mice accumulate less lactate and pyruvate because of a faster rate of pyruvate oxidation and a reduced rate of glycolysis. BCAAs (branched chain amino acids) are higher in the blood in starved PDHK4−/− mice, consistent with lower blood alanine levels and the importance of BCAAs as a source of amino groups for alanine formation. Non-esterified fatty acids are also elevated more in the blood of starved PDHK4−/− mice, consistent with lower rates of fatty acid oxidation due to increased rates of glucose and pyruvate oxidation due to greater PDC activity. Up-regulation of PDHK4 in tissues other than the liver is clearly important during starvation for regulation of PDC activity and glucose homoeostasis.
Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient
Authors: Venkataraman Krishnan , Thangada Shobha , Michaud Jason , Oo Myat Lin , Ai Youxi , Lee Yong-Moon , Wu Mingtao , Parikh Nehal S. , Khan Faraz , Proia Richard L. , Hla Timothy
Published: July 2006

Sphingosine 1-phosphate (S1P), produced by Sphks (sphingosine kinases), is a multifunctional lipid mediator that regulates immune cell trafficking and vascular development. Mammals maintain a large concentration gradient of S1P between vascular and extravascular compartments. Mechanisms by which S1P is released from cells and concentrated in the plasma are poorly understood. We recently demonstrated [Ancellin, Colmont, Su, Li, Mittereder, Chae, Stefansson, Liau and Hla (2002) J. Biol. Chem. 277, 6667–6675] that Sphk1 activity is constitutively secreted by vascular endothelial cells. In the present study, we show that among the five Sphk isoforms expressed in endothelial cells, the Sphk-1a isoform is selectively secreted in HEK-293 cells (human embryonic kidney cells) and human umbilical-vein endothelial cells. In sharp contrast, Sphk2 is not secreted. The exported Sphk-1a isoform is enzymatically active and produced sufficient S1P to induce S1P receptor internalization. Wild-type mouse plasma contains significant Sphk activity (179 pmol·min−1·g−1). In contrast, Sphk1−/− mouse plasma has undetectable Sphk activity and approx. 65% reduction in S1P levels. Moreover, human plasma contains enzymatically active Sphk1 (46 pmol·min−1·g−1). These results suggest that export of Sphk-1a occurs under physiological conditions and may contribute to the establishment of the vascular S1P gradient.