bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Treatment of Benign and Borderline Neoplasms of the Pancreatic Body
Authors: Balzano G. , Zerbi A. , Veronesi P. , Cristallo M. , Di Carlo V.
Published: September 2003

Background: Conventional operations for benign and borderline tumors of the pancreatic body are distal pancreatectomy and enucleation. An unusual operation allowing the preservation of the proximal and distal pancreas is median pancreatectomy. Method: A retrospective analysis of prospectively collected data on 67 patients with nonmalignant neoplasms of the pancreatic body was performed. The operations were: 32 median pancreatectomies (22 with duct occlusion of the distal pancreas, 10 with pancreaticojejunostomy), 21 distal pancreatectomies, and 14 enucleations. The operative and long-term outcomes of the different operations were compared. Results: Enucleation had a shorter operative time and less blood loss than the other operations. No mortality was observed. The pancreatic fistula rate was 50% after median pancreatectomy (59% in case of distal duct occlusion, 30% in case of pancreaticojejunostomy), 14% after distal pancreatectomy and 14% after enucleation. Diabetes appeared in 3 patients after distal pancreatectomy and 3 patients after median pancreatectomy with duct occlusion. Conclusions: When indicated, enucleation is the operation of choice for a nonmalignant neoplasm of the pancreatic body. With respect to distal resection, the higher fistula rate of median pancreatectomy with pancreaticojejunostomy could be the price for a better long-term endocrine function; median pancreatectomy with duct occlusion had worse operative results and no long-term advantages.
Management of Cancer of the Ampulla of Vater: Does Local Resection Play a Role?
Authors: Lindell Gert , Borch Kurt , Tingstedt Bobby , Enell Eva Lena , Ihse Ingemar
Published: September 2003

Background: The clinical outcome of patients with ampullary carcinoma is significantly more favorable than for patients with pancreatic head carcinoma. The Whipple procedure is the operation of choice for both diagnoses. Still local resection is recommended in selected cases. The aim of this study was to assess the outcome of local resection of cancer of the ampulla of Vater by comparison with pancreaticoduodenectomy. Method: 92 patients with cancer of the ampulla of Vater treated between 1975 and 1999 with local resection (n = 10), pancreatic resection (n = 49) or laparotomy and no resection (n = 33) were studied retrospectively. The main outcome measures were postoperative morbidity and mortality, surgical radicality and long-term survival. Results: The postoperative complication rate was significantly lower after local resection (p = 0.036) whereas mortality did not differ between the 2 resection groups. UICC stages were less advanced in the local resection group (p < 0.04). Still, the frequency of positive resection margins and RO resections was the same in both groups, as was long-term survival. Local recurrence was diagnosed in 8/10 (80%) patients after local and in 11/49 (22%) patients after pancreatic resection (p = 0.001). Conclusion: Pancreaticoduodenectomy is the preferred operation for cancer of the ampulla of Vater in patients who are fit for the procedure. Local resection plays a limited role in carefully selected patients.
Gastrostomy Tube Insertion into Intestinal-Cutaneous Tract Fistulas Is a New Technique to Improve Fistula Control
Authors: Halttunen Jorma , Sirén Jukka , Kivilaakso Eero
Published: September 2003

Background: The management of gastrointestinal-cutaneous fistulas may be complicated by the difficulty in obtaining adequate control of the fistula tract. This study describes a new method to obtain better fistula control utilizing a semi-rigid stent in the form of a gastrostomy tube. Methods: Consecutive patients with intestinal-cutaneous fistulas of at least 3 weeks duration and treated by the new technique were analyzed. The technique involved the insertion of a guide wire into the fistula tract from the luminal side using an endoscope, snaring the wire with a Dormia basket inserted into the fistula tract from the cutaneous side and then exteriorized. The gastrostomy tube was then pulled with the guide wire from the lumen along the fistula tract and out through the skin. Results: Five patients had had fistulas for a median duration of 42 (range 26–140) days before insertion of the gastrostomy tube. The gastrostomy tube was replaced with a smaller diameter tube in 4 of the patients (range 1–3 changes). The patients were discharged from the hospital at a median of 14 (range 12–23) days after the tube insertion but with the tube in situ. The median time from the insertion of the tube to its removal was 42 (range 32–108) days. Conclusions: Gastrostomy tube insertion using minimally invasive techniques may improve fistula control enabling patients to be discharged home sooner than otherwise and improve the rate of healing.
Splenectomy versus Spleen-Preserving Surgery for Splenic Echinococcosis
Authors: Atmatzidis K. , Papaziogas B. , Mirelis C. , Pavlidis T. , Papaziogas T.
Published: September 2003

Background/Aims: The spleen is the third most common location of hydatid disease after liver and lung. The aim of this study was to analyse the long-term outcome of surgical treatment of patients with splenic echinococcosis comparing splenectomy with spleen-preserving surgery. Methods: During a period of 25 years (1976–2001), 19 (5.4%) patients with splenic echinococcosis were treated in our department out of 349 patients with abdominal hydatid disease. In 16 patients the spleen was the only organ involved, while in 3 patients the liver was also affected. Results: Eleven patients had splenectomy and in the other 8 the spleen was preserved: enucleation (n = 4), partial cystectomy and omentoplasty (n = 2) and cystojejunal Roux-en-Y anastomosis (n = 2). One (6%) patient died in the early postoperative period and 5 (29%) patients had postoperative complications. There was no significant difference between the splenectomy and spleen-preserving groups concerning median hospital stay and postoperative complication rate. The median follow-up in 15 patients was 52 (range 6–300) months. Two patients (13%) developed recurrence of the disease requiring re-operation at 2 and 3 years, respectively. Recurrence occurred in 1 (12%) patient in the splenectomy group and in 1 (14%) out of 7 patients in the spleen-preserving group. Conclusion: In the present series it was possible to preserve the spleen in 8 (42%) of 19 patients, without significant increase of recurrent echinococcosis.
Evaluation of the POSSUM Scoring System for Comparative Audit in Pancreatic Surgery
Authors: Khan Abdaal W. , Shah Sudeep R. , Agarwal Anil K. , Davidson Brian R.
Published: September 2003

Background: Wide variations exist in the reported morbidity and mortality rates for major pancreatic resections. The Physiological and Operative Scoring System for enUmeration of Morbidity and mortality (POSSUM) was developed for comparative audit in general surgical patients. It has also been found to be reliable for audit in colorectal, thoracic and vascular surgery with minor modifications. Aims: To evaluate POSSUM and its modification for mortality, P-POSSUM, in pancreatic surgery. Methods: Retrospective analysis of 50 patients undergoing partial pancreaticoduodenectomy (PD) (46 tumours, 4 chronic pancreatitis) using the POSSUM and P-POSSUM as predictors of morbidity and mortality. These were then compared with the observed values. Results: The POSSUM-predicted mortality was 26%. The P-POSSUM predicted a mortality risk of 6%. The observed mortality was 4%. Using POSSUM for morbidity, the predicted value was 76%. The observed morbidity was 46%. The risk scores for patients with and without morbidity were similar (66.4 ± 11.0 vs. 68.8 ± 12.9, p = 0.49). Conclusions: While P-POSSUM appeared satisfactory for predicting mortality risk, POSSUM overestimated morbidity and mortality for PD in a specialist centre. Modifications are needed prior to its application for comparative audit in pancreatic surgery.
Factors Involved in the Pharmacokinetics of COL‐3, a Matrix Metalloproteinase Inhibitor, in Patients with Refractory Metastatic Cancer: Clinical and Experimental Studies
Authors: Rudek Michelle A. , Venitz Jürgen , Ando Yuichi , Reed Eddie , Pluda James M. , Figg William D.
Published: September 2003

COL‐3 is an oral, lipophilic, tetracycline analog that has been administered to patients with metastatic cancer. Preliminary assessment of COL‐3 in 35 patients with refractory metastatic carcinoma demonstrated apparent nonlinear pharmacokinetics with highly variable oral clearance (63.9% coefficient of variance [CV]). To elucidate possible sources of variability of COL‐3 pharmacokinetics in vivo, in vitro plasma protein binding and in vitro metabolism were explored along with in vivo pharmacokinetics using compartmental modeling. The variability in the overall clearance and urinary excretion of COL‐3 was also assessed. COL‐3 had a long terminal half‐life (median = 59.8 h), large apparent volume of distribution (median = 50.2 L), and low apparent clearance (median = 9.93 mL/min). Only adjusted ideal body weight decreased the variability in total apparent clearance. There was nonsaturable plasma protein binding of COL‐3 (fu = 5.5%), with the majority of binding to albumin. The renal route of elimination is negligible, with 0.06% of unchanged COL‐3 and 3.31% COL‐3 glucuronide excreted in the first 6 days. COL‐3 is not metabolized by phase I metabolism but does undergo glucuronidation in vitro by UGT1A1, UGT1A3, UGT1A9, and UGT2B7 and in vivo, as evidenced by COL‐3 glucuronides in the urine (median = 13.6% of the total dose). COL‐3 exhibits nonlinear pharmacokinetics, possibly due to dissolution rate‐limited absorption.
Effect of Mibefradil on CYP3A4 In Vivo
Authors: Veronese Maria L. , Gillen Lisa P. , Dorval Ellen P. , Hauck Walter W. , Waldman Scott A. , Greenberg Howard E.
Published: September 2003

Mibefradil, a calcium channel blocker, was removed from the market because of adverse drug interactions with coadministered CYP3A4 substrates. This study examined the effect of mibefradil on the activity of hepatic and intestinal CYP3A4 in vivo, employing the erythromycin breath test (EBT) and oral midazolam pharmacokinetics. This was a two‐period, single‐blind, placebo‐controlled crossover study in which 8 male volunteers were randomized to the order of receiving placebo and a single 100‐mg oral dose of mibefradil. Oral midazolam was coadministered with intravenous [14C N‐methyl] erythromycin 1 hour after mibefradil/placebo administration. The EBT was performed 20 minutes following erythromycin administration. Blood and urine were collected during the 36 hours following probe drug administration for analysis of midazolam pharmacokinetics. Coadministration of mibefradil increased the Cmax of midazolam 3‐fold, the AUC 8‐ to 9‐fold, and the t1/2 4‐fold. Mibefradil coadministration decreased the amount of exhaled 14CO2 in 6 of 8 subjects, with a mean decrease of 25%. It was concluded that a single oral dose of mibefradil significantly inhibits CYP3A4 in intestine and liver. These data support that adverse drug interactions involving mibefradil reflect inhibition of CYP3A4 in intestine and liver. Also, they suggest that the EBT, while a valid probe of in vivo hepatic CYP3A4 activity, is a single time point measurement and may be less sensitive than oral midazolam pharmacokinetics in detecting CYP3A4 inhibition.
Pharmacokinetics of a Novel Diltiazem HCl Extended‐Release Tablet Formulation for Evening Administration
Authors: Sista Suryanarayana , Lai John Chi‐Keung , Eradiri Okponanabofa , Albert Kenneth S.
Published: September 2003

A novel diltiazem HCl extended‐release (ER) tablet formulation was developed for evening administration in the management of angina and hypertension. Pharmacokinetics of the formulation were evaluated to identify variations in morning (7 a.m. or 8 a.m.) versus evening (10 p.m.) drug administration. Single‐dose (360 mg) and multiple‐dose (360 mg once daily for 7 days), open‐label, randomized, two‐way crossover studies of the new diltiazem HCl ER tablets were completed in 48 healthy volunteers. Serial plasma samples were collected via direct venipuncture up to 48 hours postdose and analyzed for diltiazem and its two major metabolites by high‐performance liquid chromatography (HPLC). The primary parameters used to assess the data were AUC0‐∞, AUC0‐τ, AUC6 a.m.–12 p.m., Cmax, and tmax. Statistical comparisons using ANOVA were evaluated after logarithmic transformation of dose‐dependent parameters. Diltiazem HCl ER tablets administered in the evening exhibited 17% and 22% greater bioavailability compared to morning administration under single‐dose and steady‐state conditions, respectively. The two times of drug administration were bioinequivalent in both studies. The evening schedule also provided more than twofold higher plasma diltiazem levels in the critical morning hours, when both blood pressure and the incidence of cardiovascular events are the highest.
Pharmacokinetics of Etoricoxib in Patients with Hepatic Impairment
Authors: Agrawal Nancy G. B. , Rose Mark J. , Matthews Catherine Z. , Woolf Eric J. , Porras Arturo G. , Geer Leslie A. , Larson Patrick J. , Cote Josee , Dilzer Stacy C. , Lasseter Kenneth C. , Alam Imtiaz , Petty Kevin J. , Gottesdiener Keith M.
Published: September 2003

The effect of hepatic insufficiency on the pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase‐2, was investigated following administration of single and multiple oral doses to mild hepatic insufficiency patients (Child‐Pugh score of 5 to 6), multiple oral doses to moderate hepatic insufficiency patients (Child‐Pugh score of 7 to 9), and single intravenous doses to both mild and moderate hepatic insufficiency patients. A trend of decreasing systemic clearance with increasing hepatic impairment was observed. Absorption of etoricoxib was unaffected by hepatic impairment. Binding of etoricoxib to plasma proteins was also found to be unaffected by hepatic disease. Etoricoxib was generally well tolerated by patients with mild and moderate hepatic insufficiency. Together, these results support a 60‐mg once‐daily dosing regimen for mild hepatic insufficiency patients and a 60‐mg every‐other‐day dosing regimen for moderate hepatic insufficiency patients. There are no clinical or pharmacokinetic data in patients with severe hepatic insufficiency (Child‐Pugh score > 9).
MDR1 Haplotypes Do Not Affect the Steady‐State Pharmacokinetics of Cyclosporine in Renal Transplant Patients
Authors: Mai Ingrid , Störmer Elke , Goldammer Mark , Johne Andreas , Krüger Hagen , Budde Klemens , Roots Ivar
Published: September 2003

This retrospective study investigated the impact of MDR1 haplotypes derived from the single‐nucleotide polymorphisms (SNPs) 2677G>T (exon 21) and 3435C>T (exon 26) on the pharmacokinetics of cyclosporine in 98 renal transplant patients. Based on SNPs 2677 and 3435, four different haplotypes and nine different genotypes were identified in the study sample. Frequencies of SNPs, genotypes, and haplotypes were in agreement with previously reported values. Cyclosporine pharmacokinetics were characterized using a 2‐hour AUC (AUC0–12), trough concentrations (C0), and blood concentrations 2 hours after cyclosporine administration (C2). No significant differences in dose‐corrected AUC0–12, C0, or C2 values were observed between carriers of different SNP variants and genotypes (Kruskal‐Wallis test), as well as between carriers and noncarriers of each haplotype (Mann‐Whitney U test). Carriers of haplotype 12 (2677G and 3435T), which has previously been associated with increased digoxin AUC values, had a median AUC0–12 of 18.9 μg•h•L−1 (range: 9.0–35.2) compared to 17.5 μg•h•L−1 (range: 7.5–37.1) in the noncarrier group. It was concluded that MDR1 haplotypes derived from the SNPs 2677G>T (exon 21) and 3435C>T (exon 26) are not associated with cyclosporine pharma‐ cokinetics in renal transplant patients.
Pharmacokinetic Interactions between Sirolimus and Microemulsion Cyclosporine When Orally Administered Jointly and 4 Hours Apart in Healthy Volunteers
Authors: Zimmerman James J. , Harper Dawn , Getsy Jay , Jusko William J.
Published: September 2003

Sirolimus (RAPA) and cyclosporine (CsA) are immunosuppressive compounds that are being used concomitantly in renal transplant patients. Both drugs are dosed orally, have common intestinal and hepatic metabolism and intestinal transport mechanisms, and thus offer potential for pharmacokinetic drug interactions. A single‐dose, open‐label, four‐period, four‐treatment, randomized crossover study was completed in 15 male and 6 female volunteers. Each subject received a 10‐mg oral dose of RAPA alone (Rapamune Oral Solution), a 300‐mg oral dose of CsA alone (3 × 100‐mg Neoral Soft Gelatin Capsules), RAPA and CsA jointly, and CsA followed by RAPA delayed by 4 hours. Blood samples were collected for either 144 hours (RAPA) or 48 hours (CsA) and analyzed by either liquid chromatography/tandem mass spectrometry (RAPA) or radioimmunoassay (CsA). RAPA bioavailability was markedly increased by CsA when given jointly, with Cmax, tmax, and AUC being increased 116%, 92%, and 230%, respectively. However, when RAPA was administered 4 hours after CsA, increases in RAPA Cmax, tmax, and AUC were only 37%, 58%, and 80%, respectively. CsA did not affect t1/2or mean residence time (MRT) by either mode of combined administration. RAPA did not significantly affect CsA bioavailability after either joint or delayed combined administrations. It was concluded that CsA markedly increases the bioavailability of RAPA, which may be attributed to a large intestinal and hepatic first‐pass effect, rather than altered elimination. RAPA did not affect the bioavailability of CsA.
The Pharmacokinetics of Linezolid Are Not Affected by Concomitant Intake of the Antioxidant Vitamins C and E
Authors: Gordi Toufigh , Tan Lai Hock , Hong Catherine , Hopkinsy Nancy J. , Francom Steven F. , Slatter J. Greg , Antal Edward J.
Published: September 2003

In vitro metabolism experiments have suggested a possible role for endogenous reactive oxygen species (ROS) in the in vivo clearance of linezolid, a synthetic antibiotic of the oxazolidinone class. This observation has resulted in the hypothesis that dietary antioxidant supplements might disturb the balance of ROS in vivo and thereby lower the clearance of linezolid. The purpose of this open‐label, two‐group parallel design study was to investigate whether continuous intake of widely used vitamin C or vitamin E will affect the pharmacokinetics of linezolid. A total of 28 healthy volunteers (27 male and 1 female), including 22 of Chinese origin, were administered a single oral dose of 600 mg linezolid on days 1 and 8. Half of the subjects received daily oral doses of 1000 mg vitamin C on days 2 through 9, whereas the other half were administered daily oral doses of 800 IU vitamin E during the same time period. Serial blood samples for assessment of the pharmacokinetic parameters of linezolid and its two inactive metabolites were collected on days 1 and 8, whereas vitamin concentrations were measured prior to and after the vitamin intake on these days. Urine was collected on days 1 and 8 to assess the fraction of dose excreted as linezolid and its major metabolites. All linezolid samples were analyzed according to validated HPLC/MS/MS methods. Linezolid was well tolerated in both groups with no reported clinically significant adverse events. No significant changes were found between the day 1 and day 8 AUC0‐∞ and Cmax values of linezolid in either the vitamin C treatment group (p = 0.55 and p = 0.64, respectively) or the vitamin E treatment group (p = 0.06 and p = 0.49, respectively). Assessment of other pharmacokinetic parameters did not imply any change across the study groups. In conclusion, linezolid pharmacokinetics are not affected by concomitant administration with vitamins C and E. Therefore, no dose adjustment is necessary in patients taking vitamin C or vitamin E. These no‐effect drug interaction data are in accord with current literature indicating that antioxidant vitamins have only subtle effects on overall ROS balance in vivo.
The Antiparasitic Moxidectin: Safety, Tolerability, and Pharmacokinetics in Humans
Authors: Cotreau Monette M. , Warren Sarah , Ryan John L. , Fleckenstein Lawrence , Vanapalli Sreenivasa R. , Brown Kenneth R. , Rock David , Chen Chieh‐Yu , Schwertschlag Ullrich S.
Published: September 2003

A study in healthy male volunteers was completed to evaluate the safety, tolerability, and pharmacokinetics of a single oral dose of the antiparasitic moxidectin (MOX). This drug is registered worldwide as a veterinary antiparasitic agent for use in companion and farm animals. This is the first study of MOX in humans. All subjects were between the ages of 18 and 45 years, with normal cardiac, hematologic, hepatic, and renal function. Doses of MOX studied were 3, 9, 18, and 36 mg in cohorts of 6 subjects each (5:1, MOX:placebo). At the 9‐mg and 36‐mg doses, two separate cohorts were completed, one in the fasted state and one after the consumption of a high‐fat breakfast. For all other cohorts, administration was in the fasted state. Safety and tolerability were assessed by physical examinations, ongoing evaluation of adverse events (AEs), and measurement of laboratory values. Pharmacokinetic (PK) samples were collected just prior to dosing and at various time points until 80 days postdose. Safety assessments from all dose groups studied suggested that MOX was generally safe and well tolerated, with a slightly higher incidence of transient, mild, and moderate central nervous system AEs as the dose increased as compared to placebo. The PKs of MOX were dose proportional within the dose range studied, and the elimination half‐life (t1/2 elim) was long (mean: 20.2–35.1 days). At the 9‐mg and 36‐mg doses, a high‐fat breakfast was shown to delay and increase the overall absorption but did not increase maximal concentrations when compared to administration in the fasted state. In summary, the results from this study indicate that MOX is safe and well tolerated in humans between the doses of 3 mg and 36 mg.
Teaching Cell Biology in the Large-Enrollment Classroom: Methods to Promote Analytical Thinking and Assessment of Their Effectiveness
Authors: Kitchen Elizabeth , Bell John D. , Reeve Suzanne , Sudweeks Richard R. , Bradshaw William S.
Published: September 2003

A large-enrollment, undergraduate cellular biology lecture course is described whose primary goal is to help students acquire skill in the interpretation of experimental data. The premise is that this kind of analytical reasoning is not intuitive for most people and, in the absence of hands-on laboratory experience, will not readily develop unless instructional methods and examinations specifically designed to foster it are employed. Promoting scientific thinking forces changes in the roles of both teacher and student. We describe didactic strategies that include directed practice of data analysis in a workshop format, active learning through verbal and written communication, visualization of abstractions diagrammatically, and the use of ancillary small-group mentoring sessions with faculty. The implications for a teacher in reducing the breadth and depth of coverage, becoming coach instead of lecturer, and helping students to diagnose cognitive weaknesses are discussed. In order to determine the efficacy of these strategies, we have carefully monitored student performance and have demonstrated a large gain in a pre- and posttest comparison of scores on identical problems, improved test scores on several successive midterm examinations when the statistical analysis accounts for the relative difficulty of the problems, and higher scores in comparison to students in a control course whose objective was information transfer, not acquisition of reasoning skills. A novel analytical index (student mobility profile) is described that demonstrates that this improvement was not random, but a systematic outcome of the teaching/learning strategies employed. An assessment of attitudes showed that, in spite of finding it difficult, students endorse this approach to learning, but also favor curricular changes that would introduce an analytical emphasis earlier in their training.
Animal cell division: a fellowship of the double ring?
Authors: Saint Robert , Somers W. Gregory
Published: September 2003

Despite a century of research into the nature of animal cell division, a molecular explanation for the positioning of the actomyosin contractile ring has remained elusive. The discovery of a novel interaction between regulators of Rho family small GTPases has revealed a link between the mitotic microtubules and the contractile ring during the later stages of mitosis. The properties of the interacting Rho regulators suggest a molecular model for the positioning and initiation of contractile ring furrowing in animal cells. In this `double ring' model, centralspindlin complexes, localized by the action of their kinesin-like protein component, position and activate a cortical equatorial ring of Rho GTPase exchange factors. The resulting ring of activated Rho would then trigger a cascade of events leading to formation and constriction of the contractile ring.
p97, a protein coping with multiple identities
Authors: Woodman Philip G.
Published: September 2003

A topic that is keeping cell biologists across several fields occupied is how the AAA ATPase p97 can have so many apparently unrelated functions. A recent model that proposed sets of adaptors for p97 selected according to the type of p97 activity seemed to afford a simple solution. For example, one known adaptor, the Ufd1–Npl4 complex, has been implicated in ubiquitin-dependent proteolysis whereas another, p47, is an essential co-factor for membrane fusion. However, further investigation has revealed that the situation is more complicated. Both Ufd1–Npl4 and p47 adaptors bind ubiquitin, and so their activities may be more closely related than first thought. A role for ubiquitin in p97-dependent membrane fusion is a particularly surprising development with no obvious explanation. However, some clues may be found from looking at the role of ubiquitin and the AAA ATPase Vps4 during sorting on the endocytic pathway.
Solvent-dependent cis-trans Photoisomerization of p-Methoxy-p′-nitro-substituted trans,trans,trans-1,6-Diphenyl-1,3,5-hexatriene
Authors: Sonoda Yoriko , Kawanishi Yuji
Published: September 2003

Irradiation of p-methoxy-p′-nitro-substituted 1,6-diphenyl-1,3,5-hexatriene induced trans, trans, trans → cis, trans, trans (ttt → ctt) isomerization in toluene, whereas in acetonitrile inefficient ttt → ctt, tct isomerization was observed. The results are explained in terms of weakly polar nature of twisted excited states.
Metal Nanoparticles Derived from Polysilane Shell Cross-linked Micelle Templates
Authors: Sanji Takanobu , Ogawa Yuya , Nakatsuka Yuriko , Tanaka Masato , Sakurai Hideki
Published: September 2003

Polysilane shell cross-linked micelles, where the polysilane core is surrounded by a partially cross-linked shell of poly(methacrylic acid), can be used as the template for the synthesis of metal nanoparticles.
Types of media violence and degree of acceptance in under‐18s
Authors: Ángel Vidal Miguel , Clemente Miguel , Espinosa Pablo
Published: September 2003

It is an established fact that almost every TV channel offers a high level of violent content. The object of this study is to check the degree of acceptance of this media violence in under‐18s. We will also check what cognitive and emotional effects the viewing of different types of violence has. A sample of 203 subjects aged 13 years from Madrid, Spain, viewed a clip from different films. Before and after the film, data were collected about their opinion on violence. Three viewing conditions were established according to the degree and type of violence shown and based on Berkowitz [(1996): Desclée De Brouwer]: action without violence, socially justified violence, and socially unjustified violence. Several ANOVAs were carried out revealing that violence is better valued and more attractive after watching the film sequences than before the showing. Aggr. Behav. 29:381–392, 2003. © 2003 Wiley‐Liss, Inc.
Relational aggression in college students: Examining the roles of social anxiety and empathy
Authors: Loudin Jesse L. , Loukas Alexandra , Robinson Sheri
Published: September 2003

This study examined the unique contributions of social anxiety and empathy to relational aggression in 300 19–to–25–year–old (M=21.25; SD=1.32) male (n=97) and female (n=203) college students using hierarchical linear regression analysis. The interactive relations between gender and social anxiety, and between gender and empathy, were also assessed. In addition to the gender and overt aggression covariates, fear of negative evaluation and perspective taking were unique predictors of relational aggression. Males, students who were more overtly aggressive, and those who reported greater fear of negative evaluation were more relationally aggressive than were peers. Students with higher levels of perspective taking reported using less relational aggression than did peers. A gender x empathetic concern interaction indicated that for males only, lower levels of empathetic concern were associated with higher levels of relational aggression. Results are discussed within a social information‐processing perspective. Aggr. Behav. 29:430–439, 2003. © 2003 Wiley‐Liss, Inc.
Violent video games and aggressive behavior in young women
Authors: Anderson Craig A. , Murphy Christine R.
Published: September 2003

The increasing availability of violent video games and their implication in recent school shootings has raised the volume of public debate on the effects of such games on aggressive behavior and related variables. This article reports an experiment designed to test key hypotheses concerning the short term impact of exposure to violent video games on young women, a population that has received relatively little attention in this research literature. Results were that brief exposure to a violent video game increased aggressive behavior. Mediational analyses suggested that the violent video game effect on aggression was not mediated by instrumental aggressive motivation, but was partially mediated by revenge motivation. Other results suggested that the violent video game effect on aggression might be greater when the game player controls a same‐sex violent game character. Aggr. Behav. 29:423–429, 2003. © 2003 Wiley‐Liss, Inc.
Sport team identification and willingness to consider anonymous acts of hostile aggression
Authors: Wann Daniel L. , Haynes Gaye , McLean Bryan , Pullen Paul
Published: September 2003

Previous research indicated that a sizeable minority of individuals report a willingness to consider engaging in anonymous acts of instrumental aggression directed toward players and coaches of a rival team. Individuals with a high degree of identification with their favorite team were particularly likely to consider such acts. The current investigation was designed to extend this research by examining the likelihood that individuals would consider engaging in hostile anonymous aggression. It was expected that highly identified persons would be particularly likely to consider these acts, even though the acts would not provide a competitive advantage for their team. Data collected from 175 university students confirmed the expectations. In addition, the results indicated that males were more likely than females to report a willingness to consider the hostile aggressive acts and that participants were more likely to report a willingness to engage in less destructive acts (e.g., tripping an opposing player or coach) than more destructive acts (e.g., murdering an opposing player or coach). Aggr. Behav. 29:406–413, 2003. © 2003 Wiley‐Liss, Inc.
Substance use patterns of young offenders and violent crime
Authors: Lennings C.J. , Copeland J. , Howard J.
Published: September 2003

The use of alcohol is a significant predictor of the involvement of young offenders in violent crime. This study found that in a sample of 300 incarcerated juveniles in New South Wales, more than 70% admitted to violent crime. Detainees from an Aboriginal or Torres Strait Islander culture were less likely than other detainees to be involved in violent crime. The substances most associated with violent crime were alcohol, followed by cocaine. However, when the likelihood that the young person has initiated violence as a response to alcohol or other substances is introduced into the equation, the direct effects for alcohol and cocaine predicting engagement in violent crime disappear. The Goldstein hypothesis that the effects of a substance directly facilitate violence, thereby accounting for the relationship between substances of use and violent crime, was supported. Aggr. Behav. 29:414–422, 2003. © 2003 Wiley‐Liss, Inc.
Selective attention and executive functions deficits among criminal psychopaths
Authors: Pham T.H. , Vanderstukken O. , Philippot P. , Vanderlinden M.
Published: September 2003

The present study examined whether psychopaths exhibit deficits in selective attention and executive functions. Prison inmates were assigned to either a “psychopath” group or a “control” group according to their scores on the PCL‐R [Hare, 1991: Toronto, Multi‐Health Systems]. The two groups were compared in terms of performance on the following tests: (1) D‐II cancellation, (2) Porteus Maze, (3) Modified Wisconsin Card Sorting, (4) Stroop Color Word Interference, (5) Trail Making, and (6) Tower of London. The results support the hypothesis of selective attention and specific executive function deficits among psychopaths. Specifically, psychopaths' abilities to maintain a plan and to inhibit irrelevant information were inferior to those of control participants. Aggr. Behav. 29:393–405, 2003. © 2003 Wiley‐Liss, Inc.
Rare male aggression directed toward females in a female‐dominated society: Baiting behavior in the spotted hyena
Authors: Szykman Micaela , Engh Anne L. , Van Horn Russell C. , Boydston Erin E. , Scribner Kim T. , Holekamp Kay E.
Published: September 2003

Spotted hyenas (Crocuta crocuta) are gregarious carnivores. The females are socially dominant to males, and adult males rarely direct aggression toward adult females. This study analyzed all cases in which adult immigrant males behaved aggressively toward adult females in a large population of free‐living hyenas in Kenya, observed for 11 years. Our goals were to describe the conditions under which male attacks on females occur, and address possible adaptive functions. Most aggression directed by adult immigrant males against females occurred when coalitions of two or more males attacked a single adult female, who typically responded by defending herself and fighting back. Male aggression against females frequently occurred at sites of ungulate kills, but males never behaved aggressively toward females over food, and all male attacks on females were unprovoked. Although no mounting or other copulatory behaviors ever occurred during or immediately after an attack, the number of male attacks on females peaked around the time of conception. Daily rates at which males attacked females did not vary with female social rank. However, daily attack rates did vary significantly with female reproductive state, and the highest rates of male attack on females were observed during the two stages of the reproductive cycle during which females were most likely to conceive litters. The adaptive significance of male aggression against females in this species remains unknown, but a tight association between male attacks on females and a female's time of conception provides strong evidence of some role for male aggression in hyena sexual behavior. In particular, our data are consistent with hypotheses suggesting that male aggression toward females in this species either serves to inform females about male fitness or represents sexual harassment. Aggr. Behav. 29:457–474, 2003. © 2003 Wiley‐Liss, Inc.
A linear growth curve analysis of inpatient treatment response by conduct‐disordered, ADHD, and comorbid preadolescents
Authors: Beauchaine Theodore P. , Gartner Joseph
Published: September 2003

Conduct disorder (CD) comorbid with attention deficit hyperactivity disorder (ADHD) is widely reputed to be treatment refractory, particularly when accompanied by aggression and early‐onset symptoms. Few studies, however, have assessed inpatient treatment response among early onset CD/ADHD children in detail. In the present investigation, behavioral and rating scale data were compared among CD (n=13), ADHD (n=20), and CD/ADHD (n=45) preadolescents during one‐month of multimodal inpatient treatment that included methylphenidate administration. As expected, linear growth curve analyses revealed that CD/ADHD children were the most symptomatic of the three groups. However, all groups benefited from hospitalization, with few differences in treatment responsiveness observed. Analyses of residualized symptoms suggested that methylphenidate administration was effective in curbing impulsive but not aggressive behaviors. Aggr. Behav. 29:440–456, 2003. © 2003 Wiley‐Liss, Inc.
Crystallographic report: Crystal structure of a two‐dimensional coordination polymer: dizinc diterephthalate pyrazine dihydrate
Authors: Yang Shi‐Yao , Hu Jie‐Yu , Long La‐Sheng , Huang Rong‐Bin , Zheng Lan‐Sun , Ng Seik Weng
Published: September 2003

A two‐dimensional coordination polymer [Zn2(tp)2(pz)(H2O)2]n (tp = terephthalate, pz = pyrazine) has been synthesized by the hydrothermal reaction of zinc terephthalate and pyrazine. The Zinc(II) centre is in a distorted pyramidal geometry, being coordinated by one water molecule, one nitrogen atom from a bridging pz and two different bridging tp ligands, one chelating and the other monodentate. Copyright © 2003 John Wiley & Sons, Ltd.
Assessment of fluoroalkyltin compounds as fluorous Lewis acid catalysts
Authors: Imakura Yasuo , Nishiguchi Satoru , Orita Akihiro , Otera Junzo
Published: September 2003

The synthesis of a variety of organotin compounds with 1H, 1H, 2H, 2H‐perfluorooctyl groups is reported, together with an improved method for the corresponding distannoxane. Unique properties of this compound are disclosed in terms of fluorophilicity and activity as a Lewis acid catalyst in comparison with other mono‐nuclear derivatives. A new criterion for obtaining high solubility in fluorocarbon solvents is presented. Copyright © 2003 John Wiley & Sons, Ltd.
The role of F‐actin cytoskeleton‐associated gelsolin in the guinea pig capacitation and acrosome reaction
Authors: Cabello‐Agüeros José F. , Hernández‐González Enrique O. , Mújica Adela
Published: September 2003

The acrosomal reaction (AR) is a regulated sperm exocytotic process that involves fusion of the plasma membrane (PM) with the outer acrosomal membrane (OAM). Our group has described F‐actin cytoskeletons associated to these membranes. It has been proposed that in regulated exocytosis, a cortical cytoskeleton acts as a barrier that obstructs membrane fusion, and must be disassembled for exocytosis to occur. Actin‐severing proteins from the gelsolin family have been considered to break this barrier. The present study attempted to determine if gelsolin has a function in guinea pig sperm capacitation and AR. By indirect immunofluorescence (IIF), gelsolin was detected in the apical and postacrosomal regions of the head and in the flagellum in both capacitated and non‐capacitated guinea pig spermatozoa. By Western blotting, gelsolin was detected in isolated PM and OAM of non‐capacitated spermatozoa. Gelsolin and actin were detected in a mixture of PM‐OAM obtained by sonication, and both proteins were absent in membranes of capacitated spermatozoa. Inhibition of three different pathways of PIP2 hydrolysis during capacitation did not cancel gelsolin loss from membranes. Gelsolin was detected by Western blotting associated to membrane cytoskeletons obtained after phalloidin F‐actin stabilization and Triton‐X treatment; additionally, by immunoprecipitation, it was shown that gelsolin is associated with actin. By electron microscopy we observed that skeletons disassemble during capacitation, but phalloidin prevents disassembly. A three‐dimensional skeleton was observed that apparently joins PM with OAM. Exogenous gelsolin stimulates AR assayed in a permeabilized spermatozoa model. Results suggest that gelsolin disassembles F‐actin cytoskeletons during capacitation, promoting AR. Cell Motil. Cytoskeleton 56:94–108, 2003. © 2003 Wiley‐Liss, Inc.
The ATP‐dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis
Authors: Gartner Wolfgang , Rossbacher Joerg , Zierhut Barbara , Daneva Teodora , Base Wolfgang , Weissel Michael , Waldhäusl Werner , Pasternack Mark S. , Wagner Ludwig
Published: September 2003

RUVBL1/TIP49a/Pontin52 is a recently identified multi‐functional protein with 2 ATP binding (WALKER) sites, which is essential for cell proliferation. We recovered and identified RUVBL1/TIP49a as a tubulin‐binding protein from Triton X‐100 lysates of U937 promonocytic cells by protein affinity chromatography and tryptic peptide microsequencing. Performing co‐immunoprecipitation using newly generated RUVBL1/TIP49a‐specific antibodies (mAb and rabbit polyclonal Ab) and RUVBL1/TIP49a‐GST fusion protein‐pull down assays we demonstrate co‐precipitation of α‐ and γ tubulin with RUVBL1/TIP49a. Confocal immunoflourescence microscopy reveals that RUVBL1/TIP49a was present not only in the nucleus, as expected, but was also concentrated at the centrosome and at the mitotic spindle in colocalization with tubulin. The topology of RUVBL1/TIP49a at the mitotic spindle varied, depending on the mitotic stage. The protein was localized at the centrosome and at the polar and astral microtubules in metaphase, and was detectable at the zone of polar tubule interdigitation in anaphase B and telophase. During cytokinesis the protein reappeared at the area of decondensing chromosomes. Whereas preincubation of U937 cells with colcemid resulted in inhibition of mitotic spindle formation with subsequent loss of RUVBL1/TIP49a mitotic spindle staining, no relevant influence of colcemid on RUVBL1/TIP49a‐tubulin binding was observed. An agonistic effect of RUVBL1/TIP49a on in vitro tubulin assembly is demonstrated. Our results reveal a new functional aspect of RUVBL1/TIP49a. Cell Motil. Cytoskeleton 56:79–93, 2003. © 2003 Wiley‐Liss, Inc.
Keap1 in adhesion complexes
Authors: Velichkova Michaella , Hasson Tama
Published: September 2003

Cell adhesion complexes are sensors that interact with the extracellular environment and allow for the transmission of signals found outside the cell across the plasma membrane to the cell interior. Keap1 is a newly identified component of cell adhesion complexes. We investigated Keap1's association with these complexes in diverse tissues and cell types. Keap1 is present in focal adhesion (FA)‐like assemblies in kidney proximal tubule cells where it colocates with actin. In liver, Keap1 is found in the adherens junctions (AJ) and at the base of the bile canaliculi. To study Keap1's involvement in both the integrin‐based FA and the cadherin‐based AJ, we induced formation of these complexes in fibroblasts, using a serum starvation followed by a serum supplementation method. When compared with vinculin, a component of all FA, we found that Keap1 assembles only in the peripheral FA. Within the peripheral FA, Keap1 was present in distinct foci along the length of the FA and these foci were different from vinculin, talin, paxillin, and phospho‐tyrosine rich regions of the FA. Unlike most FA components, Keap1 was also recruited to the newly formed AJ. As Keap1 homologues are actin‐bundling proteins, we hypothesize that Keap1's function is to bundle F‐actin within these diverse types of cell adhesion components. Cell Motil. Cytoskeleton 56:109–119, 2003. © 2003 Wiley‐Liss, Inc.
A Lim protein involved in the progression of cytokinesis and regulation of the mitotic spindle
Authors: Schneider Natalie , Weber Igor , Faix Jan , Prassler Josef , Müller‐Taubenberger Annette , Köhler Jana , Burghardt Emmanuel , Gerisch Günther , Marriott Gerard
Published: September 2003

DdLimE regulates cell motility and cytokinesis in Dictyostelium. To specify its function, we generated knock‐out mutants and analyzed mitosis by marking the mitotic apparatus with GFP‐α‐tubulin. Characteristic of DdLimE‐null cells is a late reversal of cytokinesis caused by backward movement of the incipient daughter cells. This process of “retro‐cytokinesis” is accompanied by a delay in disassembly of the mitotic spindle. The length of interphase microtubules is increased and their depolymerization at prophase is impaired. These data indicate that DdLimE links the cortical actin network, where it is located, to the microtubule system, whose dynamics it regulates. Cell Motil. Cytoskeleton 56:130–139, 2003. © 2003 Wiley‐Liss, Inc.
Orientation of the central pair complex during flagellar bend formation in Chlamydomonas
Authors: Mitchell David R.
Published: September 2003

Thin section electron micrographs of rapidly fixed Chlamydomonas cells were used to establish a relationship between flagellar bends and orientation of the central pair microtubule complex. Using conditions that preserve flagellar waveforms during both forward swimming (asymmetric bends) and backward swimming (symmetric bends), we found that central pair orientation differs in bent regions and straight regions. During forward swimming, a plane through the two central pair microtubules is parallel to the bend plane throughout principal bends, in both effective stroke and recovery stroke phases of the beat cycle. In these curved segments, the C1 microtubule always faces the outer edge of the curve. This parallel orientation twists in straight regions both proximal and distal to bends. During backward swimming episodes induced by photoshock, when Chlamydomonas flagella beat with principal and reverse bends of similar magnitude, the central pair twists by 180 degrees between successive bends. These observations support a model in which central pair orientation in Chlamydomonas is linked to doublet‐specific dynein activation, and bend propagation is linked to rotation of the central pair complex. Cell Motil. Cytoskeleton 56:120–129, 2003. © 2003 Wiley‐Liss, Inc.
Cell filtration‐laser scanning cytometry for the characterisation of circulating breast cancer cells
Authors: Zabaglo Lila , Ormerod Michael G. , Parton Marina , Ring Alistair , Smith Ian E. , Dowsett Mitch
Published: September 2003

Background

Epithelial cells may be detected in the circulation of the majority of patients with metastatic breast cancer. Quantification of such presumptive cancer cells might allow for the monitoring of patients with early or late stage disease as an early index of relapse. Additionally, biomarker analysis may allow a more rational approach to therapeutics. We have developed a new method for the detection and characterisation of these cells.

Methods

Blood was filtered through polycarbonate membranes containing cylindrical pores, 8 μm in diameter. All the red cells and a large majority of the white blood cells passed through the filter while the larger epithelial cells were trapped. Cells on the membrane were fixed in ethanol, stained with propidium iodide and anti‐pan‐cytokeratin‐FITC (to identify epithelial cells). The filters were then examined by laser scanning cytometry (LSC), which allowed enumeration and localisation of cells.

Results

With normal blood spiked with cells from breast carcinoma cell lines, 99.9% of the leukocytes passed through the membrane, while close to 100% of the epithelial cells were trapped, with a detection limit of less than one epithelial cell/ml of blood. All of 20 samples from patients with widespread metastatic disease contained cytokeratin‐positive cells with the morphological characteristics of carcinoma cells, the number of cells ranging from 0.2 to 5.7/ml of blood.

Conclusions

Cell filtration‐LSC is a viable technique for detecting and studying breast carcinoma cells in peripheral blood. Cytometry Part A 55A:102–108, 2003. © 2003 Wiley‐Liss, Inc.