bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of L‐tyrosine confirming its safe human use as an adjuvant
Authors: Baldrick Paul , Richardson Derek , Wheeler Alan W.
Published: October 2002

Although there is a long history of exposure to allergy vaccines containing L‐tyrosine, there has been no central publication reviewing its adjuvant properties in animal and human studies together with an assessment of its safe use. This paper summarizes a range of investigational data (unpublished) available to the authors as well as published literature reports. An array of in vitro and in vivo studies showed that L‐tyrosine has ideal adjuvant properties, comprising a high adsorptive power for proteins, enhancement of IgG antibody induction with no stimulatory effect on IgE antibody level and action as a short‐term depot adjuvant, delaying the bioavailability of allergenic materials rather than directly influencing immunocompetent cells. A series of preclinical safety investigations comprised single‐dose parenteral studies in the mouse and rat, repeat‐dose parenteral toxicity studies over 28 days in the rat and dog (up to 25 mg kg−1 day−1) plus genotoxicity and local tolerance studies. No signs of toxicity or genotoxicity were seen; repeat‐dose toxicity studies showed expected white cell and spleen weight immunostimulatory effects; local‐dose site reactions were also seen and were confirmed in local tolerance studies. Findings from a range of clinical studies using allergy vaccines containing L‐tyrosine reflected the lack of toxicity seen in animal work and showed evidence of enhanced immunostimulatory activity. Local injection site reactions (a common response to any form of clinical vaccination) in these studies were likely to be due to the presence of L‐tyrosine per se. The lack of findings of toxicological concern found during this review supports the hypothesis that L‐tyrosine is a safe adjuvant for human use. Copyright © 2002 John Wiley & Sons, Ltd.
Expression of glutathione transferase isoenzymes in the human H295R adrenal cell line and the effect of forskolin
Authors: Stark Tuula , Mankowitz Louise , DePierre Joseph W.
Published: October 2002

In previous studies in our laboratory (L. Mankowitz, L. Staffas, M. Bakke, and J. Lund, Biochem J, 1995, 305, 111–118; L. Staffas, L. Mankowitz, M. Söderström, A. Blanck, I. Porsch‐Hällström, C. Sundberg, B. Mannervik, B. Olin, J. Rydström, and J.W. DePierre, Biochem J, 1992, 286, 65–72) isoenzymes of GST, primarily of the μ class, have been shown to be downregulated by adrenocorticotropic hormone (ACTH) in rat and mouse adrenal cells. In the present investigation the human adrenal H295R cell line (W.E. Rainey, I.M. Bird, and J.I. Mason, Mol Cell Endocrinol, 1994, 100, 45–50) was examined in a similar manner. Analysis by reverse‐phase HPLC revealed that these cells express four isoenzymes of GST, i.e., A1, A2, P1, and M4, as well as another unidentified protein that was retained by our affinity column (elution time of 32 min) and, thus, presumably binds glutathione. Among these forms, A1 was present at the highest level. Upon addition of forskolin (an activator of adenylate cyclase which has been shown previously to mimic the effect of ACTH on adrenal cells) to the culture medium, the level of A1 decreased approximately 70% by forskolin, whereas the levels of the other isoenzymes were slightly increased, and that of the unknown form doubled. Thus, the influence of ACTH on expression of GST isoenzymes in this human adrenal cell line differs from that in rat and mouse adrenal cells. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:169–173, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10034
Alteration of thrombine‐signaling mechanism by heptachlor in human platelets
Authors: Moya de Juri María G. , Magnarelli de Potas Gladis , Pechen de D'Angelo Ana M.
Published: October 2002

Heptachlor is a persistent organochlorine insecticide that has been detected in human tissues and fluids. The ability of heptachlor to interfere with platelet phosphoinositides metabolism and related signaling events stimulated by thrombin was evaluated. In vitro incubations with a concentration range of 1–100 μM heptachlor, prior to platelets activation, were performed. Experiments showed that 10 μM increased protein Kinase C (PKC) activity and phosphatidylinositolbiphosphate and phosphatidic acid phosphorylation. Simultaneously phosphatidylcholine and phosphatidylethanolamine breakdown were prevented. Similar effects were observed with HC 1 μM. However, heptachlor 100 μM increased phosphatidylinositolbiphosphate phosphorylation but reduced serine/threonine kinases activity. We propose that signal transduction steps downstream phospholipase C (PLC) are unphysiologically activated by heptachlor and facilitated by the increase in phosphatidylinositolbiphosphate, the substrate for PLC activity, thus producing an accumulation of phosphatidic acid. The elevated level of this compound itself or the transient increase in diacylglycerol produced may cause calcium mobilization and the activation of PKC. In contrast with the alterations observed in phospholipids and protein phosphorylation, no changes in aggregation properties were observed. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:189–196, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10037
How to slash your worldwide travel costs
Authors: Miller Mark
Published: October 2002

Here's a strategy that can cut all your travel costs by more than 20 percent—without affecting

performance or customer satisfaction. © 2002 Wiley Periodicals, Inc.
Innovation: Your stealth weapon against global competition
Authors: Shapiro Stephen
Published: October 2002

CEOs are on edge from a series of shocks: the dotcom meltdown; post‐9/11 market drop;

Enron; and a declining global economy. To make matters worse, there's increasing resistance as U.S.

companies try to expand globally. What's the answer? You must create a business that can adapt quickly

and flexibly to change, says the author. And the way to do it is to inject innovation into decision making

throughout your company. Here are some strategies that work. © 2002 Wiley

Periodicals, Inc.
Surviving culture clash: How to read German financial statements
Authors: Goldberg Stephen R. , Godwin Joseph H.
Published: October 2002

As global business expands, more U.S. firms want to buy foreign companies—or invest in them, form

alliances, or extend credit to them. So U.S. firms examine foreign companies' financial statements to

gauge the risk. But cultural— as well as accounting—differences can get in the way. For example,

financial statements for German companies can befuddle a U.S. reader. What must you know to really understand

them? © 2002 Wiley Periodicals, Inc.
Two views of employee behavior
Authors: Goldberg Stephen R. , Godwin Joseph H.
Published: October 2002

Niven, Paul R. 2002. Balanced Scorecard, Step‐by‐Step (New York: John

Wiley and Sons).

Pickett, K. H. Spencer, and Jennifer M. Pickett. 2002. Financial Crime Investigation and

Control (New York: John Wiley and Sons).
Ketoconazole potentiates terfenadine‐induced apoptosis in human Hep G2 cells through inhibition of cytochrome p450 3A4 activity
Authors: Wang Ying‐Jan , Yu Cheng‐Fei , Chen Li‐Ching , Chen Chien‐Ho , Lin Jen‐Kun , Liang Yu‐Chih , Lin Chien‐Huang , Lin Shyr‐Yi , Chen Chin‐Fa , Ho Yuan‐Soon
Published: October 2002

Terfenadine (TF) is a highly potent histamine H1 receptor antagonist that in clinically effective doses is free of significant central nervous system side effects. Ketoconazole (KT) is a worldwide used oral antifungal agent with a broad spectrum of activity against both superficial and systemic mycosis. Simultaneously administration of KT and TF has been reported to induce several potent symptoms including cardiotoxicity, excitotoxicity, inhibition of blood mononuclear cells proliferation, and cardiovascular toxicity. However, the intracellular molecular mechanisms of TF–KT interactions in cells were still uncertain. In this study, we first demonstrated that TF (5–30 μM) induced apoptosis in several types of human cancer cell lines including human hepatoma (Hep G2), colorectal cancer (COLO 205), and fibroblast (CCD 922SK) cells for 24 h. The cellular responses to TF‐induced apoptosis were demonstrated to be associated with the p53‐signaling pathway, including induction of p53, p21/Cip1, p27/Kip1, bax protein expression and inhibition of bcl‐2 protein expression. To realized the role of H1 receptor involved in TF‐induced apoptosis, different H1 receptor antagonists including promethazine, mequitazine, and chlorpheniramin (50–100 μM) were administered and demonstrated that these chemicals cannot induced apoptosis through the H1 receptor signaling pathway. Interestingly, we found that the apoptotic effect of TF (2.5 μM) was significantly potentiated by KT (1 μM) treatment in Hep G2 cells through inhibition of the cytochrome p450 3A4 (CYP 3A4) activity. Such results were demonstrated by decreased of the TF activity with recombinant CYP 3A4, which prepared from baculovirus‐infected insect cells. Our results provide the molecular basis of TF–KT interaction and this information should allow more rational forecasting of the risk for TF therapy during co‐administration of KT. J. Cell. Biochem. 87: 147–159, 2002. © 2002 Wiley‐Liss, Inc.
New partial difference sets in p‐groups
Authors: Hou Xiang‐Dong
Published: October 2002

Latin square type partial difference sets (PDS) are known to exist in R × R for various abelian p‐groups R and in ℤt. We construct a family of Latin square type PDS in ℤt × ℤ2ntp using finite commutative chain rings. When t is odd, the ambient group of the PDS is not covered by any previous construction. © 2002 Wiley Periodicals, Inc. J Combin Designs 10: 394–402, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10029
Polymorphisms for interleukin‐4 (IL‐4) –590 promoter, IL‐4 intron3, and tumor necrosis factor alpha –308 promoter: Non‐association with endometriosis
Authors: Hsieh Yao‐Yuan , Chang Chi‐Chen , Tsai Fuu‐Jen , Hsu Yuan , Tsai Horng‐Der , Tsai Chang‐Hai
Published: October 2002

Interleukin‐4 (IL‐4) is a cytokine with anti‐inflammatory properties. Tumor necrosis factor alpha (TNF‐α), a pluripotent proinflammatory cytokine, plays an important role in the process of numerous inflammatory and autoimmune diseases. We aimed to investigate whether gene polymorphisms for the IL‐4 –590 promoter, IL‐4 intron3 and TNFα –308 promoter could be used as markers of susceptibility in endometriosis. The subjects, 226 premenopausal Taiwan Chinese women with surgically diagnosed endometriosis and nonendometriosis, were divided into two groups: 1) endometriosis (n = 120) and 2) nonendometriosis (n = 106). Polymorphisms for the IL‐4 –590 promoter, IL‐4 intron3, and TNFα –308 G‐to‐A promoter were detected by polymerase chain reaction (PCR). Genotypes and allelic frequencies for these gene polymorphisms in both groups were compared. We observed no significant differences in genotype distribution and allele frequency of the IL‐4 –590 promoter, IL‐4 intron3, and TNFα gene polymorphism between both groups. The proportions of the –590*C homozygote/heterozygote/–590* T homozygote for the IL‐4 promoter in both groups were 1.6/31.6/66.6% in group 1, and 5.8/33.0/61.2% in group 2. The proportions of the RP1 homozygote/heterozygote/RP2 homozygote for IL‐4 intron3 in both groups were 62.5/34.1/2.5% (group 1), and 64.1/32.0/3.9% (group 2). The proportions of –308*A homozygote/heterozygote/–308*G homozygote for the TNFα promoter in both groups were 7.5/20.8/71.7% (group 1), and 7.5/17/75.5% (group 2). We concluded that there is no association between endometriosis and the IL‐4 and TNFα gene polymorphisms. The IL‐4 –590 promoter, IL‐4 intron3, and TNFα –308 G‐to‐A polymorphisms are not useful markers for predicting susceptibility to endometriosis. J. Clin. Lab. Anal. 16:121–126, 2002. © 2002 Wiley‐Liss, Inc.
Use of the eie‐recombinant‐chagas‐biomanguinhos kit to monitor cure of human chagas’ disease
Authors: Silva Edimilson D. , Pereira Valéria R.A. , Gomes Juliana A.S. , Lorena Virgínia Maria B. , Cançado Joaquim R. , Ferreira Antonio G.P. , Krieger Marco Aurélio , Goldenberg Samuel , Correa‐Oliveira Rodrigo , Gomes Yara M.
Published: October 2002

We used the EIE‐Recombinant‐Chagas‐Biomanguinhos kit (EIE‐Rec kit) developed by the Oswaldo Cruz Foundation, Brazil, to monitor cure of chagasic patients who were treated during the acute phase of T. cruzi infection. Treated patients were previously studied by parasitological and serological tests and classified as cured patients (CP) (n = 10), dissociated patients (DP) (n = 6), and noncured patients (NCP) (n = 6). When sera of these patients were assayed by EIE‐Rec kit all sera from NCP and all sera from CP showed positive and negative reactions, respectively. These results were in full agreement with those obtained previously by the classical tests. Two DP showed a positive reaction; the remaining four displayed a negative reaction, similar to that observed in sera from nonchagasic (NCh) individuals, and could therefore be considered CP. Our results suggest that the EIE‐Rec kit could be used to monitor the efficacy of Chagas’ disease treatment. J. Clin. Lab. Anal. 16:132–136, 2002. © 2002 Wiley‐Liss, Inc.
Evaluation of a single‐step multiplex RT‐PCR for influenza virus type and subtype detection in respiratory samples
Authors: Poddar Saibal K. , Espina Rowena , Schnurr David P.
Published: October 2002

A single‐step multiplex reverse transcription‐polymerase chain reaction (RT‐PCR) for the simultaneous detection of influenza virus type and subtypes was evaluated for its use in clinical specimens. One part of each specimen was tested using an established standard culture and/or monoclonal antibody‐based immunofluorescence assay method, and the other part was tested by the multiplex RT‐PCR method for the presence or absence of the influenza virus, and its type and subtype. Sixty‐seven specimens were examined. The results revealed a strong agreement between the data obtained by the established method and those obtained by the multiplex RT‐PCR. J. Clin. Lab. Anal. 16:163–166, 2002. © 2002 Wiley‐Liss, Inc.
Robotic inhibition assay for determination of HMG‐CoA reductase inhibitors in human plasma
Authors: Fang Wei , Liu Lida , Hsieh John Y.‐K. , Zhao Jamie , Matuszewski Bogdan K. , Rogers John D. , Dobrinska Michael R.
Published: October 2002

The cholesterol‐lowering drug simvastatin (SIMV, Zocor®) reduced heart attacks by 42% in patients who had high cholesterol levels and suffered from heart disease. Upon oral administration, SIMV is quickly hydrolyzed to its β‐hydroxyacid and other acid metabolites, which are potent inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase. A Tecan‐based enzyme inhibition assay has been developed to improve the existing Zymark‐based assay for the determination of both active and total concentrations of HMG‐CoA reductase inhibitors in human plasma. A Tecan Genesis 200 robotic workstation equipped with eight probes and customized hardware was utilized to achieve higher sample throughput and improve assay reproducibility and mechanical stability. The developed enzyme inhibition assay was validated over two concentration ranges of 0.4–20 ng equivalent/mL, and 2–50 ng equivalent/mL. Intra‐ and interday precision data (coefficient of variation (CV)) for both concentration ranges were less than 9%, with an accuracy of 93–107%. The interday precision for the determination of quality control (QC) samples was less than 2% and 8%, respectively. The respective interday QC accuracy values were 93–103% and 97–104%. Good linearity across the two concentration ranges was observed, with acceptable reproducibility. This improved enzyme inhibition assay has been utilized to analyze human plasma samples from several clinical studies. J. Clin. Lab. Anal. 16:209–215, 2002. © 2002 Wiley‐Liss, Inc.
Reference distributions for serum iron and transferrin saturation: a practical, simple, and clinically relevant approach in a large cohort
Authors: Ritchie Robert F. , Palomaki Glenn E. , Neveux Louis M. , Navolotskaia Olga , Ledue Thomas B. , Craig Wendy Y.
Published: October 2002

The principal considerations driving iron status evaluation are clinical concern for anemia and the possibility of iron‐storage disease. Most often, the circulating levels of transferrin (or total iron binding capacity) and serum iron are measured and the percentage of transferrin saturation (TSAT) is then computed. Optimally, reference ranges for these analytes should exclude the effects of the acute phase response, nutritional status, estrogen effect, specific genetic disorders, liver disease, and blood transfusion. The current study reports reference ranges for serum iron and TSAT within a cohort of over 55,000 Caucasians from northern New England, tested in our laboratory between 1994 and 1999. Measurements were standardized against serum reference material (SRM) 937 (for iron) and certified reference material (CRM) 470 (also called reference preparation for proteins in human serum (RPPHS)) (for transferrin), and analyzed using a previously published approach. Individual cases with evidence of inflammation (C‐reactive protein ≥10 mg/L), or iron overload (TSAT >80% for males and >70% for females) or serum iron values <5 μmol/L, were removed. Among the referent individuals, iron and TSAT levels rose slightly until the teen years, at which time levels in males increased while those in females remained essentially constant. Between 20 and 70 years of age, males had 10–15% higher iron levels and 15–20% higher TSAT levels than females. When values were expressed as multiples of the age‐ and gender‐specific median levels, the serum iron and TSAT observations fit log‐Gaussian distributions reasonably well from the 20th to 99th centile, and the 10th to the 99th centile, respectively. After normalization, the Gaussian parameters can be used to assign a corresponding centile to an individual's measurement, simplifying interpretation. These data provide new and more detailed reference ranges for serum iron and TSAT. J. Clin. Lab. Anal. 16:237–245, 2002. © 2002 Wiley‐Liss, Inc.
MPS screening methods, the berry spot and acid turbidity tests, cause a high incidence of false‐negative results in sanfilippo and morquio syndromes
Authors: Chih‐Kuang Chang , Shuan‐Pei Lin , Shyue‐Jye Lee , Tuen‐Jen Wang
Published: October 2002

Because of differences in the types and quantities of glycosaminoglycans (GAGs) in various mucopolysaccharidoses (MPSs), MPS screening tests, including the Berry spot and acid turbidity tests, are not specific or sensitive enough for the preliminary diagnosis of MPS. A false‐negative result is common. We analyzed urine samples collected from 492 patients who were examined for inborn errors of metabolism using the Berry spot and acid turbidity (qualitative and quantitative) tests. Of those, 48 MPS patients (seven with MPS I, 17 with MPS II, nine with MPS III, 11 with MPS IV, and four with MPS VI) underwent preliminary differentiation between MPS types by two‐dimensional electrophoresis (2D‐EP), and were confirmed by enzymatic assay. Approximately 21.0% and 7.1% of the 492 samples showed positive reactions in the Berry spot and acid turbidity tests, respectively. Of these, a total of 35 samples with MPS types I, II, and VI showed strong positive reactions in both tests. Five patients with Sanfilippo (MPS III) and six patients with Morquio (IV) syndromes showed false‐negative results in both tests. In our study, approximately 13.8% (68 in 492 samples) samples showed a positive reaction in the Berry spot test but a negative one in the acid turbidity test, for unknown reasons. The Berry spot and acid turbidity tests are used extensively for the preliminary diagnosis of MPS in Asia; however, the possibility of a misdiagnosis of MPS type III and IV with both tests should be kept in mind. For accurate diagnosis and confirmation of MPS, the 2D‐EP method and enzymatic assay are recommended. They provide high sensitivity, specificity, and efficiency in diagnosing MPS. J. Clin. Lab. Anal. 16:253–258, 2002. © 2002 Wiley‐Liss, Inc.
Porphobilmogen deaminase gene mutations in Brazilian acute intermittent porphyria patients
Authors: Ribeiro Georgina Severo , Marchiori Paulo Eurípedes , Kuntz Puglia Paula Marzorati , Nagai Maria Aparecida , dos Santos Mariana Lopes , Nonoyama Kimiyo , Hirata Mário Hiroyuki , Barretto Orlando C.O.
Published: October 2002

Acute intermittent porphyria (AIP) is an autosomal dominant disorder resulting from porphobilmogen deaminase (PBGD) deficiency. Seven unrelated Brazilian patients were investigated regarding PBGD gene mutations by polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) analysis followed by direct DNA sequencing. The PBG gene screening disclosed abnormal SSCP patterns in exons 7, 9, 12, 13, and 15, as well as in introns 3 and 10. Direct DNA sequencing revealed the occurrence of three nonsense mutations (R149X, R225X, and R325X) in exons 9, 12, and 15, respectively, and one missense mutation G111R in exon 7. The G111R mutation was detected in two unrelated patients. Intragenic polymorphisms (3119G/T in intron 2, 3581G/A in intron 3, 7052A/G and 7064C/A in intron 10, and −65C/T in exon 1) were also observed. In addition, two silent mutations (V202V in exon 10 and A266A in exon 13) were found. The latter has not heretofore been reported. Thus, this study revealed the mutations involved in Brazilian symptomatic AIP patients, as well as the intragenic polymorphisms found in the patients. J. Clin. Lab. Anal. 16:259–265, 2002. © 2002 Wiley‐Liss, Inc.
Internship placement data: Is nonplacement the only concern?
Authors: Oehlert Mary E. , Sumerall Scott W. , Lopez Shane J. , Merkley Katherine B.
Published: October 2002

Current discussion regarding securing internships often focuses on their availability. Thus, quantity is especially emphasized. However, quality is also an issue of importance. The number of intern applicants receiving slots at quality internship sites, as defined by the internship having been accredited by the American Psychological Association or having successfully been reviewed by the Association of Psychology and Postdoctoral Internship Centers, was assessed. Information regarding the number of unfunded internships also was gathered. Recommendations for increasing the availability of quality internships are provided. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1323–1326, 2002.
Practice‐informed research and research‐informed psychotherapy
Authors: Lueger Robert J.
Published: October 2002

The information processing demands of planning and conducting psychotherapy and the types of information that clinicians value potentially can inform research that is likely to be useful to clinicians. Four approaches to conducting research on psychotherapy issues—technology transfer studies, quasi‐experimental single‐case designs, mental health services research, and case‐focused patient profiling—have the potential to inform the practicing therapist. These approaches generally are either treatment focused or patient focused, and can vary in their relevance to the individual case. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1265–1276, 2002.
Exploring links between childhood maltreatment and empowerment
Authors: Banyard Victoria L. , LaPlant Lindsey E.
Published: October 2002

Empowerment theory may be useful in understanding the long‐term impact of child maltreatment yet to date few studies have bridged these fields. The current study of female undergraduates was exploratory and examined links between a history of child maltreatment and several dimensions of empowerment. Factor analysis was used to create indices of intrapersonal sense of empowerment, community connections, and social action from various measures related to empowerment cited in the community psychology literature. Higher levels of reported maltreatment were related to lesser interpersonal sense of empowerment and self‐report of lower levels of community connections even after controlling for the effects of negative family of origin environment. Implications for theory, research, and interventions are discussed. © 2002 Wiley Periodicals, Inc.
Justice and local community change: Towards a substantive theory of justice
Authors: Drew Neil M. , Bishop Brian J. , Syme Geoff
Published: October 2002

Justice is a core principle in community psychology, yet has been the subject of relatively little systematic research. In the social psychological literature on the other hand there is a long tradition of research on justice in social life. In this article the potential benefits of integrating the social justice aspirations of community psychology and the conceptualizations of procedural and distributive justice from social psychology are discussed in the context of planned community change. The benefits of exploring justice in this way are illustrated with reference to a research project examining public perceptions of the fairness of roadside tree lopping. Although the issue may appear trivial, it was seen by the local residents as important. The results support the development, application, and utility of a social community psychology of justice to issues of community change. © 2002 Wiley Periodicals, Inc.
The effect of headspace pressure on the performance of a fluidised‐bed bioreactor
Authors: Fung C J
Published: October 2002

This study compares the biological performance of three fluidised‐bed biological reactors under conditions of different headspace pressures. The application of pressure can have a profound effect on the initial rate of bed growth. However, once the fluidised‐bed reaches full expansion, the biological performance at higher pressures is greater than those at lower pressures. There appears to be an almost linear relationship between the application of pressure and the performance of the fluidised‐bed biological reactors in removing soluble BOD5. This can be attributed to the increase in the oxygen concentration in the bulk liquid and a greater oxygen penetration depth within the biofilm.

© 2002 Society of Chemical Industry
Kinetics of esterification of lauric acid with fatty alcohols by lipase: effect of fatty alcohol
Authors: Shintre M S , Ghadge R S , Sawant S B
Published: October 2002

Lauric acid has been esterified with some C1–C18 aliphatic alcohols by a commercial lipase, Lipolase 100 L, using isooctane as a solvent. When lauric acid and fatty alcohols were taken in the mole ratio 1:1, first order kinetics were observed for all the alcohols studied. The highest reaction rate was observed for n‐butyl alcohol. Lauric acid was esterified with stearyl alcohol, in varying acid to alcohol mole ratios to explain the first order kinetics of the reaction. A kinetic model for the lipase‐catalysed esterification in a biphasic organic–aqueous system has been proposed. Based on the interfacial substrate concentration, an analytical rate equation for initial rate of the reaction was derived and confirmed with the experimental data.

© 2002 Society of Chemical Industry
Solitary metastasis from renal cell carcinoma presenting as diffuse pancreatic enlargement
Authors: Chou Yi‐Hong , Chiou Hong‐Jen , Hong Tun‐Mei , Tiu Chui‐Mei , Chiou See‐Ying , Su Cheng‐Hsi , Tsay Shyh‐Haw
Published: October 2002

Late metastasis of renal cell carcinoma (RCC) to the pancreas is uncommon. Diffuse pancreatic metastasis of any carcinoma rarely causes global enlargement of the pancreas. We present the case of a 73‐year‐old man diagnosed with metastatic RCC of the pancreas 9 years after radical nephrectomy had been performed and describe our radiologic findings. The disease involved the entire pancreas, which was hypoechoic on sonography, hypodense on CT without contrast enhancement, and markedly hyperdense after intravenous administration of a contrast agent. Color Doppler sonography showed that the involved areas of the pancreas had increased color flow signals, indicating that the metastatic tumor was characteristically hypervascular. In patients with a history of RCC, color or power Doppler sonographic demonstration of diffuse enlargement of the pancreas with evidence of hypervascularity may indicate metastasis of RCC to the pancreas. © 2002 Wiley Periodicals, Inc. J Clin Ultrasound 30:499–502, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jcu.10104
Gallbladder contractility in patients with cirrhotic versus malignant ascites
Authors: Sari Ramazan , Yildirim Bulent , Sevinc Alper , Bahceci Funda , Hilmioglu Fatih
Published: October 2002

Purpose

The aim of this study was to evaluate differences in gallbladder contractility by measuring gallbladder wall thickness, fasting and residual gallbladder volume, and gallbladder ejection fraction in patients with cirrhotic and malignant ascites.

Methods

Twenty‐four patients (16 women and 8 men) with malignant ascites (2 cervical, 2 colon, 2 stomach, 6 pancreatic, and 12 ovarian carcinomas), aged 59 ± 12 years, and 26 patients (14 women and 12 men) with cirrhotic ascites, aged 57 ± 16 years, were included in the study. After patients fasted overnight for 8 hours, gallbladder wall thickness, fasting gallbladder volume, and gallbladder volume and ejection fraction were measured sonographically at 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after ingestion of a standard liquid test meal.

Results

The mean gallbladder wall thickness was higher in patients with cirrhotic ascites than in those with malignant ascites (5.5 ± 1.5 mm [standard deviation] versus 3.1 ± 0.6 mm, respectively; p < 0.001). The mean fasting gallbladder volume was also higher in patients with cirrhotic ascites than in those with malignant ascites (27.3 ± 11.5 cm3 versus 17.6 ± 8.9 cm3; p < 0.05). Patients with cirrhotic ascites had significantly higher mean postprandial gallbladder volumes and ejection fractions than did those with malignant ascites at all times except 10 minutes after the meal (p < 0.05).

Conclusions

Our findings suggest that gallbladder contractility is greater in patients with cirrhotic ascites than in patients with malignant ascites. © 2002 Wiley Periodicals, Inc. J Clin Ultrasound 30:477–480, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jcu.10108
The cytoskeleton in fish melanophore melanosome positioning
Authors: Sköld Helén Nilsson , Aspengren Sara , Wallin Margareta
Published: October 2002

Melanophore melanosomes organelles can be regulated to move and locate correspondingly to many other different organelle types. Comparing lessons from analysis of a specific melanosome distribution can, therefore, contribute to the understanding of distribution of other organelles, and vice versa. From such data, it is now generally accepted that microtubules provide directed long‐distance movement, while cell peripheral movements include microfilaments. In fish melanophores, both actin and dynein exhibit counter‐forces to the kinesin‐like protein in maintaining the evenly dispersed state, while actin and kinesin exhibit counter‐forces to dynein in many other systems. Lessons from elevating cAMP levels indicate the presence of a peripheral feedback regulatory system involved in maintaining the evenly dispersed state. Studies from dynein inhibition suggest that the kinesin‐like protein involved in fish melanosome dispersal is regulated in contrast to many other systems. One would further expect melanosome transport to be regulated also on actin/myosin, in order to prevent actin‐dependent capture of melanosomes during the microtubule‐dependent aggregation and dispersion. General findings will be discussed in comparison with positioning and movement of other organelle types in cells. Finally, recent data on melanosome‐dependent organising of microtubules show that dynein is involved in nucleating microtubules extending from melanosome aggregates in melanophore fragments. Microsc. Res. Tech. 58:464–469, 2002. © 2002 Wiley‐Liss, Inc.
The physiology of flatfish chromatophores
Authors: Burton Derek
Published: October 2002

Most flatfish, of the order Pleuronectiformes, possess a white lower side, and a brown or grey upper side. This upper side can display integumentary patterning with dark areas and colored or white spots. Chromatophores in flatfish are dermal and epidermal melanophores, as well as dermal xanthophores, erythrophores, iridophores, and leucophores, combinations of which contribute to the color and patterning. Cellular studies demonstrate pattern‐related differences in numerical distribution between the types of chromatophores, and in their size, both of which will enhance contrast between areas of the pattern. As well as these morphological characteristics, there are also clear physiological differences, with melanophores from various areas of the patterns demonstrating differential responsiveness to background and to stress/excitement stimuli. Regulation of flatfish melanophore responses is predominantly neural, through the sympathetic nervous system; the pituitary hormones in these fish function in maintaining final equilibria in physiological adaptations to backgrounds. Melanophores from main components of patterns also respond differently in vitro to electrical stimulation, to pituitary hormones, and to sympathomimetic drugs and their antagonists. Sensitivity characteristics with α‐ and β‐adrenergic pharmacological reagents in vitro indicate the existence of a pattern‐related balance in α‐ and β‐adrenoceptor mediation in melanophore regulation. The patterning mechanism is complex, with both morphological and physiological differences at the chromatophore level, as well as involvement of central processing and control, which remains to be analysed. Microsc. Res. Tech. 58:481–487, 2002. © 2002 Wiley‐Liss, Inc.
Image analysis and morphometry in the diagnosis of breast cancer
Authors: Gil Joan , Wu Haishan , Wang Beverly Y.
Published: October 2002

Image Analysis, a complicated field still in the early stages of application to Pathology, has the capability of rendering major contributions to the diagnosis, prognosis, and management of malignancies of the breast. The present review summarizes the main problems and the general approach to the use of this technique for quantitating immunohistochemical stain results, obtaining DNA histograms, and making de novo diagnoses in routine materials of the Pathology service. In the case of diagnosis, the main steps are sampling, segmentation, and measures of chromatin texture. Currently, the limiting factor for all routine applications of image analysis is probably the absence of a reliable automatic nuclear segmentation. Microsc. Res. Tech. 59:109–118, 2002. © 2002 Wiley‐Liss, Inc.
Ingeneue: A versatile tool for reconstituting genetic networks, with examples from the segment polarity network
Authors: Meir Eli , Munro Edwin M. , Odell Garrett M. , Von Dassow George
Published: October 2002

Here we describe a software tool for synthesizing molecular genetic data into models of genetic networks. Our software program Ingeneue, written in Java, lets the user quickly turn a map of a genetic network into a dynamical model consisting of a set of ordinary differential equations. We developed Ingeneue as part of an ongoing effort to explore the design and evolvability of genetic networks. Ingeneue has three principal advantages over other available mathematical software: it automates instantiation of the same network model in each cell in a 2‐D sheet of cells; it constructs model equations from pre‐made building blocks corresponding to common biochemical processes; and it automates searches through parameter space, sensitivity analyses, and other common tasks. Here we discuss the structure of the software and some of the issues we have dealt with. We conclude with some examples of results we have achieved with Ingeneue for the Drosophila segment polarity network. J. Exp. Zool, (Mol. Dev. Evol.) 294:216–251, 2002. © 2002 Wiley‐Liss, Inc.
Long cycles in 3‐connected graphs in orientable surfaces
Authors: Sheppardson Laura , Yu Xingxing
Published: October 2002

In this article, we apply a cutting theorem of Thomassen to show that there is a function f: N → N such that if G is a 3‐connected graph on n vertices which can be embedded in the orientable surface of genus g with face‐width at least f(g), then G contains a cycle of length at least cn, where c is a constant not dependent on g. © 2002 Wiley Periodicals, Inc. J Graph Theory 41: 69–84, 2002
Minor‐order obstructions for the graphs of vertex cover 6
Authors: Dinneen Michael J. , Xiong Liu
Published: October 2002

We provide for the first time, a complete list of forbidden minors (obstructions) for the family of graphs with vertex cover 6. This study shows how to limit both the search space of graphs and improve the efficiency of an obstruction checking algorithm when restricted to k–VERTEX COVER graph families. In particular, our upper bounds 2k + 1 (2k + 2) on the maximum number of vertices for connected (disconnected) obstructions are shown to be sharp for all k > 0. © 2002 Wiley Periodicals, Inc. J Graph Theory 41: 163–178, 2002
Hall parameters of complete and complete bipartite graphs
Authors: Cropper M. M. , Hilton A. J. W.
Published: October 2002

Given a graph G, for each υ ∈V(G) let L(υ) be a list assignment to G. The well‐known choice number c(G) is the least integer j such that if |L(υ)| ≥j for all υ ∈V(G), then G has a proper vertex colouring ϕ with ϕ(υ) ∈ L (υ) (∀υ ∈V(G)). The Hall number h(G) is like the choice number, except that an extra non‐triviality condition, called Hall's condition, has to be satisfied by the list assignment. The edge‐analogue of the Hall number is called the Hall index, h′(G), and the total analogue is called the total Hall number, h″(G), of G. If the stock of colours from which L(υ) is selected is restricted to a set of size k, then the analogous numbers are called k‐restricted, or restricted, Hall parameters, and are denoted by hk(G), h′k(G) and h″k(G).

Our main object in this article is to determine, or closely bound, h′(K), h″(Kn), h′(Km,n) and h′k(Km,n). We also answer some hitherto unresolved questions about Hall parameters. We show in particular that there are examples of graphs G with h′(G)−h′(G − e)>1. We show that there are examples of graphs G and induced subgraphs H with hk(G)<hk(H) [this phenomenon cannot occur with unrestricted Hall numbers]. We also give an example of a graph G and an integer k such that hk(G)<χ(G)<h(G). © 2002 Wiley Periodicals, Inc. J Graph Theory 41: 208–237, 2002
Rural‐to‐urban migration in LDCS: a test of two rival models
Authors: Bhattacharya Prabir C.
Published: October 2002

This paper provides a test—using an India data set—of both the Todaro‐type probabilistic models of migration and a distinctly different view of the labour migration process which sees the rural–urban migration flow as consisting of two distinct streams, with separate incentives—one group migrating to the informal sector where wages are competitively determined and the other group to the formal sector with jobs mostly prearranged (and with rural–urban migration not contributing to an increase in unemployment in any meaningful sense). The policy implications of this alternative view of the labour migration process are clearly substantially different from those derived from the Todaro and the Harris–Todaro‐type models. The evidence presented in this paper are seen to support this alternative view. The paper also considers the role of the social factors in migration decisions and examines the extent to which the variables which explain the migration for employment also explain the migration behaviour of those who gave various reasons other than employment for migration. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of deuterium‐labelled coenzyme Q10
Authors: Hamamura Kimio , Yamagishi Yoji , Kijima Shizumasa , Suzuki Takeshi , Mori Yutaka , Nakamura Tetsuya
Published: October 2002

Deuterium‐labelled coenzyme Q10 ([2‐CD3‐1′‐CD2]coenzyme Q10, coenzyme Q10‐d5 ) was synthesized by condensation of 2,3‐dimethoxy‐[5‐CD3]methyl‐1, 4‐hydroquinone with [1‐CD2]decaprenol. Five positions were selected for deuteration as replacement at these positions allowed examination of every step of the synthesis. This examination was carried out by a combination of 1H‐ and 13C‐nuclear magnetic spectrometry and mass spectrometry. Further, these positions have been proved to be metabolically stable. This reagent makes simultaneous quantification of the source of coenzyme Q10 (exogenously supplied or endogenously supplied) possible in biological samples by measurements on gas chromatography–mass spectrometry. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of [3′‐14C] coenzyme Q10
Authors: Hamamura Kimio , Yamatsu Isao , Minami Norio , Yamagishi Yoji , Inai Yuichi , Kijima Shizumasa , Nakamura Tetsuya
Published: October 2002

Radio‐labelled coenzyme Q10, labelled at the 3′‐position with 14C, was synthesized starting from natural solanesol and ethyl [3‐14C] acetoacetate. The radiochemical yield was 8.0% from ethyl [3‐14C] acetoacetate. The specific radioactivity of the product was 44.8 μCi, 1.66 MBq/mg. The specific radioactivity and radiochemical purity are sufficiently high to enable us to use this labelled form of coenzyme Q10 in metabolic studies. Copyright © 2002 John Wiley & Sons, Ltd.
Efficient synthesis and formulation of (R)‐(−)‐[11C]Deprenyl, a selective radioligand for the quantification of MAO‐B activity using PET
Authors: Dolle Frédéric , Bramoulle Yann , Hinnen Françoise , Fowler Joanna S.
Published: October 2002

Carbon‐11 labeled (R)‐(−)‐Deprenyl is the tracer of reference for the quantification of monoamine oxidase (MAO)‐B activity with PET. In this paper, its radiosynthesis is re‐investigated and oriented towards the preparation of multi‐milliCuries of radiotracer. Typically, using no‐carrier‐added [11C]methyl triflate as the alkylating agent, 140–190 mCi (5.1–7.0 GBq) of (R)‐(−)‐[11C]Deprenyl was obtained within 30 min of radiosynthesis (including HPLC purification and formulation) with specific radioactivities ranging from 0.8 to 1.2 Ci/μmol (29.6–44.4 GBq/μmol). The high efficiency of these radiosyntheses allows for multi‐injection protocols and kinetic approaches for absolute quantification of the tracer. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis and preliminary PET study of the 5‐HT7 receptor antagonist [11C]DR4446
Authors: Zhang Ming‐Rong , Haradahira Terushi , Maeda Jun , Okauchi Takashi , Kida Takayo , Obayashi Shigeru , Suzuki Kazutoshi , Suhara Tetsuya
Published: October 2002

DR4446 (1‐methyl‐2a‐[4‐(4,5,6,7‐tetrahydrothieno[3,2‐c]pyridin‐5‐yl)butyl]‐2a,3,4,5‐tetrahydro‐1H‐benz[cd]indole‐2‐one) is a potent 5‐HT7 receptor antagonist (Ki=9.7 nM) with a high selectivity over other 5‐HT family receptors (Ki for 5‐HT1A: 770 nM; for other 5‐HT receptors: >1000 nM). As a positron emission tomography (PET) tracer for the 5‐HT7 receptor, [11C]DR4446 was synthesized at high radiochemical purity ( >98%) with specific activity of 73–120 GBq/μmol at the end of synthesis by the alkylation of the desmethyl precursor (1) with [11C]CH3I in the presence of NaH. A PET study in monkey demonstrated that [11C]DR4446 had good permeability into the brain, and had a specific binding component in the brain regions including the thalamus, possibly an area in the 5‐HT7 receptors. Metabolite analysis showed that [11C]DR4446 was relatively stable and low percentages of two radio‐labeled metabolites were detected in the plasma of monkey using HPLC. Copyright © 2002 John Wiley & Sons, Ltd.
From chiral bromo[13,14Cn]acetyl sultams to complex molecules singly/multiply labelled with isotopic carbon
Authors: Voges R.
Published: October 2002

The chiral bromo[13,14Cn]acetyl sultams (+)‐ and (−)‐[13,14Cn]BABS 1a, 1b have been demonstrated to be highly efficient, versatile and practical synthons to numerous enantiomerically pure singly and multiply labelled building blocks. The trichlorotitanium enolates derived from 1a, 1b undergo aldol addition reactions with aldehydes providing easily purified, crystalline syn‐2‐bromo‐3‐hydroxy [13,14Cn]carboxylic acid derivatives with excellent diastereo‐selectivity. These can serve as starting materials for e.p. singly/multiply labelled α‐substituted β‐hydroxy acids, β‐substituted/branched α‐hydroxy acids and α‐unsubstituted β‐hydroxy acids. Furthermore, 1a, 1b can be easily converted to the (+)/(−)‐[13,14Cn]DPMGBS 6, (+)/(−)‐[13,14Cn]ITCABS 8 and (+)/(−)‐[13,14Cn]PABS 10 synthons, which significantly enlarges the spectrum of readiliy accessible intermediates. 6 Provides e.p. labelled α‐amino acids, 8 can be employed for the preparation of e.p. labelled α‐amino‐β‐hydroxy acids (threonine type). Synthon 10 reacts with aldehydes to chiral E‐configured enoyl sultams 11 which serve as starting materials for a broad variety of e.p. singly/multiply labelled α,β‐substituted/branched, acyclic and cyclic carboxylic acid derivatives. Finally, aldehydes, generated by reductive cleavage of the auxiliary from the primary α,β‐substituted acyl sultams, react with Ph3P=COOR to give γ,δ‐substituted α,β,‐unsaturated esters, which in turn can be readily converted to highly functionalized e.p. labelled intermediates. This methodology has been extensively exploited for the synthesis of a broad spectrum of carbon‐14 labelled drug substances e.g. Taxol, Valsartan, Everolimus, Lipid X, NVP IMM125, SDZ ISQ844, SDZ PRI05 and the cyclosporin derivatives Valspodar, NVP IMM125, NVP NIM811. Copyright © 2002 John Wiley & Sons, Ltd.
Development of phenotypic differences in sensillum populations on the antennae of a grasshopper, Schistocerca americana
Authors: Chapman R.F.
Published: October 2002

The development of diet‐induced phenotypic differences in numbers of sensilla on the antennae of the grasshopper Schistocerca americana was studied using the exuviae produced at each molt. This made it possible to follow changes within an individual insect. In the first instar, insects had similar numbers of four sensillum types: uniporous trichoid sensilla, coeloconic sensilla, and large and small multiporous basiconic sensilla. Rearing on lettuce resulted in sixth instars with greater numbers of three sensillum types than siblings reared on an artificial diet. The first statistically significant differences between treatments in numbers of trichoid sensilla and large basiconic sensilla occurred in the third and fourth instars, respectively. No major reductions in sensillum numbers occurred at any time and the phenotypic differences resulted from differences in the numbers added at each molt. J. Morphol. 254:186–194, 2002. © 2002 Wiley‐Liss, Inc.
Nuclear medicine applications in molecular imaging
Authors: Blankenberg Francis G. , Strauss H. William
Published: October 2002

With the emergence of the new field of molecular imaging, there is an increasing demand for development of sensitive and safe novel imaging agents that can be rapidly translated from small animal models into patients. Nuclear medicine and positron emission tomography (PET) techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes, usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at doses free of pharmacologic side effects, unlike the current generation of intravenous agents required for magnetic resonance (MR) and computed tomography (CT) scanning. In this article, we will review a representative sampling of the wide array of radiopharmaceuticals developed specifically for nuclear medicine radionuclide imaging that have been approved for clinical use, and those in pre‐clinical trials. We will also review the existing strategies used to select the appropriate biologic markers and targets for radionuclide labeling that have been employed in the development of novel radiotracers and the imaging of small animals with new microSPECT (single photon emission computed tomography) technologies. J. Magn. Reson. Imaging 2002;16:352–361. © 2002 Wiley‐Liss, Inc.