bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Subforms of Free Prostate-Specific Antigen in Serum by Two-Dimensional Gel Electrophoresis: Potential to Improve Diagnosis of Prostate Cancer
Authors: Jung Klaus , Reiche Janett , Boehme Axel , Stephan Carsten , Loening Stephan A , Schnorr Dietmar , Hoesel Wolfgang , Sinha Pranav
Published: October 2004

Background: The aim of this study was to develop a method to separate and quantify subforms of free prostate-specific antigen (fPSA) in serum by two-dimensional electrophoresis and to assess the diagnostic accuracy of these subforms for prostate cancer (PCa) diagnosis in comparison with total PSA (tPSA) and the ratio of fPSA to tPSA (%fPSA).

Methods: Sera from 50 patients with and without PCa, respectively, were studied. PSA was isolated by immunoadsorption on streptavidin-coated magnetic beads with biotinylated anti-PSA antibodies and separated by two-dimensional electrophoresis. After semidry blotting, the intensities of the fPSA spots were quantified by chemiluminescence using an imager analyzer.

Results: The method detected subforms to a concentration of 0.1 μg/L fPSA with an imprecision (CV) <16%. We detected 15 immunoreactive fPSA spots of different intensities. Spots F2 and F3 were present in all samples. F2 was lower in samples from non-PCa patients (median, 23%) than in samples from PCa patients (49%), whereas F3 behaved inversely (non-PCa, 73%; PCa, 45%). Ratios of F2 to F3 and F2/F3 to %fPSA, respectively, showed improved diagnostic accuracy compared with tPSA and %fPSA. Better differentiation by F2/F3 or by F2/F3 to %fPSA was particularly evident in patients with %fPSA values >15%. There were no associations between the PCa grading scale and fPSA subforms.

Conclusions: fPSA subforms separated by two-dimensional electrophoresis may improve both sensitivity and specificity in prostate cancer diagnostics compared with tPSA and %fPSA. The development of a practicable assay based on the immunologic properties of these different fPSA subforms seems to be promising.
A Learning-Based Model for Imputing Missing Levels in Partial Conjoint Profiles
Authors: Bradlow Eric T. , Hu Ye , Ho Teck-Hua
Published: October 2004

Respondents in a conjoint experiment sometimes are presented with successive partial product profiles. First, the authors model how respondents infer missing levels of product attributes in a partial conjoint profile by developing a learning-based imputation model that nests several extant models. The advantage of this approach over previous research is that it infers missing levels of an attribute not only from prior levels of the same attribute but also from prior levels of other attributes, especially ones that match the attribute levels of the current product profile. Second, the authors provide an empirical demonstration of their approach and test whether learning in conjoint studies occurs; to what extent; and in what manner it affects responses, partworths, and the relative importance of attributes. They show that the relative importance of attribute partworths can shift when subjects evaluate partial profiles, which suggests that consumers may construct rather than retrieve partworths and are sensitive to the order in which the profiles are presented. Finally, the results show that consumers' imputation processes can be influenced by manipulating their prior information about a product category. This research is of both theoretical and practical importance. Theoretically, this research sheds light on how customers integrate different sources of information in evaluating products with incomplete attribute information; practically, it highlights the potential pitfalls of imputing missing attribute levels using simple rules and develops a better behavioral model for describing and predicting customers' ratings for partial conjoint profiles.
Coordinating Price Reductions and Coupon Events
Authors: Anderson Eric T. , Song Inseong
Published: October 2004

In this article, the authors use an economic model to show that it may be optimal to lower the retail price during a coupon event when marginal consumers have moderate hassle costs of coupon redemption. Results from the model offer predictions on the relationships among coupon redemptions, shelf price, and coupon face value. The authors test these predictions on a large data set of hundreds of coupon events across six packaged goods categories. The data show that when a small coupon face value is offered, the shelf price is likely to be reduced. They also find that coupon efficiency increases when there is a lower retail price. The results are of interest to managers planning a promotion calendar and deciding whether to coordinate price promotions with coupon events, and they contribute to economic theory. When a firm moves from uniform pricing (e.g., no coupons) to second-degree price discrimination (e.g., coupons), all consumers may face a lower price. This finding has public policy implications because second-degree price discrimination may increase the welfare of every consumer.
Analyzing Brand Competition across Subcategories
Authors: Wedel Michel , Zhang Jie
Published: October 2004

The authors develop a sales model that can be used to assess cross-category price effects that are specific to individual items (stockkeeping units) from store-level sales data. Previous cross-category studies have typically assumed that the cross-category effects are the same across brands or items because the potential number of price effects to be estimated is large. The authors address this problem by decomposing the variability of cross-category price effects into two components: variability across items and across stores. They capture the variability across items by representing the item-level parameters as draws from distributions with category-level means. They account for variability across stores through a random-effects factor structure that represents the variation of within- and between-category price effects separately. The model is calibrated on weekly store sales data of items in three orange juice subcategories (refrigerated, frozen, and shelf-stable). The authors study competition between national brands and private labels across the subcategories, for which their model lends itself well. The results show asymmetrical price competition not only within but also across subcategories: the cross-subcategory impact of national brands on store brands appears to be substantially greater than that of store brands on national brands. In addition, the model supports the implementation of price zones at a more granular level than the current practice.
Incidental Prices and Their Effect on Willingness to Pay
Authors: Nunes Joseph C. , Boatwright Peter
Published: October 2004

Previous research has explored how both internal and external references prices affect consumer perceptions and consequently the price that consumers are willing to pay for a product or service. Historically researchers have examined the effects of exposure to prices for the same product, the same brand, or products in the same category. This research explores the effect of incidental prices on the consumer's willingness to pay. The authors define incidental prices as prices advertised, offered, or paid for unrelated products or goods that neither sellers nor buyers regard as relevant to the price of an item that they are engaged in selling or buying. More specifically, the authors examine how prices for products that buyers encounter unintentionally can serve as anchors, thus affecting willingness to pay for the product that they intend to buy. The findings have important implications for auction houses and online vendors as well as for conventional retailers.
Vertical Marketing Systems for Complex Products: A Triadic Perspective
Authors: Wuyts Stefan , Stremersch Stefan , Van Den Bulte Christophe , Franses Philip Hans
Published: October 2004

Products that require extensive and complex information flows among suppliers, intermediary vendors, and customers often pose particular challenges to the vertical marketing system. Using social network theory, the authors investigate buyers' preferences for specific patterns of relationships among buyers, intermediary vendors, and suppliers of complex products. Using a conjoint experiment with actual and prospective buyers of integrated computer networks and services, the authors find that beyond their dyadic interaction with a vendor, buyers take into account the buyer-vendor-supplier triad. Specifically, buyers value sequences of selective strong ties as well as sequences of more numerous weak ties. This is consistent with theoretical propositions that strong ties facilitate the mobilization of support and the transfer of complex knowledge, whereas nonoverlapping weak ties facilitate the gathering of intelligence and the monitoring of new developments. The authors find only mixed evidence that buyers value direct access to suppliers when strong ties exist between the vendor and suppliers, as predicted by the third-party sanctioning argument in social network theory. In addition, they find that interaction intensity and valence do not always have the same effects, thus providing criterion validation to the bidimensional nature of tie strength that has been documented in previous research.
Paraoxonase as a Risk Marker for Cardiovascular Disease: Facts and Hypotheses
Authors: Laplaud P. Michel , Dantoine Thierry , Chapman M. John
Published: October 2004

Paraoxonase (PON1) is a Ca2+-dependent enzyme whose mechanism of action is incompletely elucidated. PON1 was originally found to be responsible for the hydrolysis of paraoxon, a catabolite of the insecticide parathion, but this enzyme is equally able to hydrolyze other substrates such as phenyl acetate. PON1 exhibits two sequence polymorphisms, Arg →Gln 192 and Met →Leu 55, respectively, of which the former is responsible for the distinct catalytic activity of the two corresponding allozymes against paraoxon. The PON1 gene is a member of a family of at least three related genes. Although the physiologic substrate of PON1 is unknown, a protective role against the oxidative degradation of serum lipoproteins has been attributed to this enzyme. Indeed, PON1 is a component of a spectrum of circulating high density lipoprotein particles and can hydrolyze oxidized phospholipids and cholesteryl ester hydroperoxides. Studies have been conducted to evaluate the possible “protective” role of PON, and especially the influence of the Arg→Gln 192 polymorphism, in coronary artery disease. Results from these investigations are conflicting, and recent data suggest a complex pattern with influences from other polymorphisms in either the PON1 and/or the PON2 and PON3 genes, or even another region of the gene cluster. A number of related factors, which include the heterogeneity of the high density lipoprotein particles incorporating PON(s), the metabolism of associated apolipoproteins such as apoJ/clusterin, the respective roles of PON(s) and other high density lipoprotein-associated enzymes such as platelet-activating-factor acetyl-hydrolase and lecithin-cholesterol acyltransferase, modifications of high density lipoprotein composition and activity under acute-phase conditions, the dietary and environmental regulation of PON(s), and the actualin situavailability of PON in the atherosclerotic artery wall, must equally be taken into account.
Influence of Time and Temperature on Coagulation Analytes in Stored Plasma
Authors: Heil Wolfgang , Grunewald Regina , Amend Martin , Heins Michael
Published: October 2004

There is no comprehensive study on the stability of coagulation analytes in plasma. We therefore determined the influence of storage time and temperature on prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, factors V and VIII, antithrombin III, protein C and S in plasma from 20 healthy subjects and 20 patients receiving heparin therapy. The stability in plasma, defined as the period during which there was a change of less than 10 % from the initial value, was 8 hours for activated partial thromboplastin time, 24 hours for prothrombin time, 48 hours for factor V and 7 days for thrombin time, fibrinogen, protein C and antithrombin III in healthy subjects at 6 °C. Factor VIII and protein S showed 19 and 12 % reduction in activity, respectively, after 8 hours.

In volunteers not treated with heparin therapy, activated partial thromboplastin time was stable for 8 hours; prothrombin time for 48 hours; and thrombin time, fibrinogen and antithrombin III for 7 days with sample storage at room temperature. Factor VIII showed a decrease of 18 % after 8 hours.

For patients receiving heparin therapy, the stability of the analytes in plasma stored at 6 °C was 8 hours for thrombin time, 24 hours for prothrombin time and activated partial thromboplastin time and 7 days for fibrinogen and antithrombin III. Factors V and VIII showed a decrease of 13 % and 20 % respectively after 8 hours.

When the plasma of these patients was stored at room temperature, factor V was stable for 8 hours, and prothrombin time for 24 hours, whereas fibrinogen and antithrombin III remained unchanged for 7 days. Activated partial thromboplastin time showed an increase of 13 %, thrombin time a fall of 16 %, and factor VIII a decrease of 18 % after 8 hours.
Biological Day-to-Day Variation and Daytime Changes of Testosterone, Follitropin, Lutropin and Oestradiol-17β in Healthy Men
Authors: Ahokoski Outi , Virtanen Arja , Huupponen Risto , Scheinin Harry , Salminen Eeva , Kairisto Veli , Irjala Kerttu
Published: October 2004

Information on biological day-to-day variation is needed for detecting within-subject changes over time. In this study the daytime changes and the biological day-to-day variation of serum testosterone, follitropin, lutropin and oestradiol-17β concentrations were investigated in 31 healthy males.

To analyse daytime changes, blood specimens were taken at 0800 h, 1200 h, 1600 h and 2000 h during one day (n=31) and two days (n=8). The day-to-day variation was analysed from blood specimens collected at 0800 h on days 1 and 2 (n=31) and additionally on days 3, 4, 6 and 9 (n=8). The evaluation of the day-to-day variation was based on calculations of the within-subject (CVA+I) and between-subject (CVG) coefficients of variation. When the within-subject day-to-day variances were not too heterogeneous, they were used for the calculation of 95 % reference change limits.

Serum testosterone and oestradiol-17βconcentrations showed a significant daytime variation; testosterone had higher serum concentrations at 0800 and 1200 h. A peak in the serum concentration of oestradiol-17β occurred at 1200 h with a decrease towards the evening. There were no clear daytime changes in the serum concentrations of follitropin or lutropin.

For different analytes the reference change limits were: serum testosterone ± 32.0 %, serum follitropin ± 24.1 % and serum oestradiol-17β ± 38.3 %. The reference change limit was not calculated for serum lutropin, as a high degree of heterogeneity and individuality was found.

The interpretation of the results of hormone measurements requires recognition of the biological daytime and day-to-day changes of hormones. The reference change limits determine what changes are significant when monitoring the patient.
Mutation Detection and Mutation Databases
Authors: Cotton Richard G. H.
Published: October 2004

Detection of mutations in genes is vital throughout biology, however, this activity is time-consuming, expensive and requires a high degree of skill. This is unsatisfactory in a field which is increasing importance. Around 10–12 methods are commonly used with some predominating. All have their advantages and disadvantages and none is perfect. Sequencing is said to be the gold standard for detecting new mutations (and must be used to define it), but six or so methods have been described to make the search quicker to avoid sequencing the whole gene. These are called scanning methods. Other methods are used to detect known mutations and referred to as diagnostic methods. These methods will be briefly reviewed. Once mutations are described, they are usually published. The mutation lists are collected for convenience, analysis or research. In recent years, it has been realised that these lists are vital for research, patient care and commercial activities. These activities will be reviewed and the co-ordinating role of the HUGO Mutation Database Initiative will be outlined.
Oligonucleotide-Based Gene Therapy for Cardiovascular Disease
Authors: Morishita Ryuichi , Nakagami Hidenori , Taniyama Yoshiaki , Matsushita Hidetsugu , Yamamoto Kei , Tomita Naruya , Moriguchi Atsushi , Matsumoto Keiko , Higaki Jitsuo , Ogihara Toshio
Published: October 2004

Gene therapy is emerging as a potential strategy for the treatment of cardiovascular disease such as restenosis after angioplasty, vascular bypass graft occlusion, transplant coronary vasculopathy, homozygous familial hypercholesterolemia and cystic fibrosis, for which no known effective therapy exists. Gene therapy requires efficient in vivo gene transfer technology. During the past decade, many gene transfer methods including viral transfer techniques have been developed, and some are being applied clinically in human gene therapy studies. Molecular biology and pathophysiology of the cardiovascular system have started to emerge, and the time is ripe for the introduction of gene therapy to the management of cardiovascular disorders. In this review, we have focused on the future potential of oligonucleotide-based gene therapy for the treatment of cardiovascular disease.
Simple and Broadly Applicable Sample Preparation by Use of Magnetic Glass Particles
Authors: Bartl Knut , Wenzig Peter , Kleiber Joerg
Published: October 2004

A key issue in nucleic acid-based assays related to infectious disease testing and genetic testing is the sample preparation. This has to be convenient, efficient and suitable for automation.

We describe a new method based on the use of glass magnetic particles. The steps involved are the lysis of bacterial cells and viral particles by chaotropic salts, binding of released nucleic acids to the magnetic glass particles, the removal of inhibitors and the release of purified nucleic acids ready for PCR amplification. The method fulfills most of the requirements for sample preparation such as sensitivity, universality and suitability for automation.
Optimized Non-Radioactive Protein Truncation Test for Mutation Analysis of the Adenomatous Polyposis Coli (APC) Gene
Authors: Kirchgesser Michael , Albers Andreas , Vossen Rolf , den Dunnen Johan , van Ommen Gert-Jan , Gebert Johannes , Dupont Cecile , Herfarth Christian , von Knebel-Doeberitz Magnus , Schmitz-Agheguian Gudrun
Published: October 2004

Germline mutations in the adenomatous polyposis coli gene cause familial adenomatous polyposis, a colon cancer predisposition syndrome. More than 95% of the identified mutations result in the generation of stop codons or reading frame shifts and encode a truncated gene product, a mutation profile also found in other tumor predisposition genes such as the breast cancer or the hereditary non-polyposis coli. Therefore the protein truncation test is ideally suited for screening of mutations in these genes, starting from simple blood samples. Gene segments of interest are amplified from genomic DNA or mRNA, thereby incorporating a T7 promoter at the 5′-end. After in vitro transcription and translation of the PCR products, the resulting protein is analysed by gel electrophoresis. Truncated translation products indicate the presence of a stop mutation. We have developed a non-radioactive protein truncation test that uses a biotinylated Lys-t-RNA to label the translation products and allows a chemiluminescent detection instead of the standard radioactive method. This generic protein truncation test kit was then used to develop a parameter-specific protein truncation test for adenomatous polyposis coli. The adenomatous polyposis coli gene was divided in 5 overlapping segments, and primers were optimized to produce distinct bands with very low background in the protein truncation test. The assay was tested on 20 familial adenomatous polyposis patient samples, where 18 mutations were found, demonstrating the efficiency of this method.
Monitoring of Inhibitors of Enzymatic Amplification in Polymerase Chain Reaction and Evaluation of Efficacy of RNA Extraction for the Detection of Hepatitis C Virus Using the Internal Control
Authors: Miyachi Hayato , Masukawa Atsuko , Ohshima Toshio , Fusegawa Hisae , Hirose Toru , Impraim Chaka , Ando Yasuhiko
Published: October 2004

Inhibitors of enzymatic amplification in serum may cause false-negative results for direct detection of hepatitis C virus (HCV) by polymerase chain reaction (PCR). This study was undertaken to demonstrate the importance of the internal control in a PCR assay for detection of HCV-RNA to monitor false-negatives due to inhibitors. HCV-RNA was extracted using RNA extraction kit (SepaGene RV-R, Sanko Junyaku) and a prototype instrument for automated specific capture of HCV-RNA with probes and magnetic bead/fluid separation (Roche Molecular Systems). The extracted HCV-RNA and internal control were detected by an automated PCR machine (Cobas Amplicor, Roche Diagnostic Systems). Addition of hemoglobin (up to 4.5 g/l) to the sera followed by RNA extraction with SepaGene RV-R had no inhibitory effect on the detection of either HCV-RNA or the internal control. In contrast, addition of heparin to the sera showed an inhibitory effect with a dose-dependent manner on the detection of both HCV-RNA and the internal control, with a greater effect at lower copy number of HCV. When HCV-RNA was extracted by the automated system, the inhibitory effect of heparin was successfully eliminated. In the assays of 65 serum samples positive for anti-HCV antibodies, positivity for the internal control indicated efficient amplification and validated 14 negative and two equivocal results for detection of HCV-RNA. Detection of the internal control was negatively correlated with viral copy number in sera suggesting competitive inhibition of high viral copy number on amplification of the internal control. Extraction, coamplification and detection of the internal control appears useful for estimating effects of inhibitors on amplification in each assay for the detection of HCV-RNA, and for evaluating efficacy of RNA extraction methods.
Automation of Polymerase Chain Reaction-Based Systems for Detection of Hepatitis C Virus RNA
Authors: Kessler Harald H. , Pierer Karen , Santner Brigitte I. , Vellimedu Srinivas K. , Stelzl Evelyn , Marth Egon
Published: October 2004

Polymerase chain reaction-based molecular assays are gaining increasing importance in the diagnosis and monitoring of infectious diseases. Over the past several years, the development and application of these techniques has initiated a revolution in the diagnosis and monitoring of hepatitis C infection. Presently, molecular assays are exclusively done in especially dedicated laboratories. Advances in automation will bring these technologies into routine diagnostic laboratories and will make them widely used.
Restriction Digest PCR (RD-PCR) for the Analysis of Gene Mutations. Application to Ki-ras
Authors: Huber Klaus Roland , Bittner Jürgen , Bauer Kurt , Trümper Lorenz , Sek Alexandra , Sebesta Christian , Rosen Harald , Tragl Karl-Heinz
Published: October 2004

The Kirsten-ras (onco)gene codes for a GTP-binding membrane protein that is involved in signal transduction. Activated ras triggers a cascade of protein-phosphorylations that ultimately lead to cell proliferation. Ras-mutations are the main cause for adenocarcinomas of the pancreas besides some mutations in the tumor suppressor gene p53 and the c-erbB-2 oncogene. The site of ras mutations in pancreatic cancer is restricted to codon 12 that normally encodes a glycine. For analysis of codon-12 mutations, DNA is extracted from cells in pancreatic fluid and amplified by PCR. Because most of these cells originate from normal tissue with only a few tumor cells in the fluid, “enrichment PCR” must be utilized: In a first round of the PCR, ras sequences from all cells are amplified. By utilizing an appropriate restriction enzyme, wild-type sequences can be digested and the remaining fragments containing mutated sequences be amplified again. An artificial restriction site must be introduced by the 5′ primer (…GGA C̱CT GGT…) for an enzyme (BstNI) (5′CC!WGG 3′) to differentiate between wild-type sequence (…GGA G̱CT GGT…) (during amplification, the G̱ is replaced by a C̱) and mutated sequences (̱…GGA GCT (GTT), (CGT), (CCT), etc.). The necessary manipulations pose a considerable risk for contamination for the second round of the PCR procedure. Therefore, we considered whether it would be feasible to perform the restriction digest simultaneously with the first PCR reaction, and avoiding the secound round altogether.

The results of our experiments demonstrate that one tumor cell in 1000 normal cells can be determined readily, paralleling the results with the original two step-assay. The restriction enzyme used to enrich mutated sequences is stable long enough to be included into the PCR procedure. By this, wild-type sequence amplicons are digested while they are formed and mutated sequences can be enriched selectively.
Direct Detection of Mycobacterium tuberculosis in Respiratory Specimens Using an Automated DNA Amplification Assay and a Single Tube Nested Polymerase Chain Reaction (PCR)
Authors: Yam Wing Cheong , Yuen Kwok Yung , Seto Wing Hong
Published: October 2004

The performance of an automated DNA amplification assay (Roche Cobas® Amplicor™ Mycobacterium Tuberculosis Test (aPCR) was compared with an in-house single tube nested polymerase chain reaction (nPCR) for the direct detection of Mycobacterium tuberculosis in respiratory specimens. Among 385 specimens, 56 were culture positive for mycobacteria (44 positive for Mycobacterium tuberculosis and 12 positive for nontuberculosis mycobacteria). The diagnostic sensitivities of aPCR and nPCR were 86 % and 91 % whereas a 100 % diagnostic specificity of both assays was attained. By aPCR, inhibitors were detected in 6% of the clinical samples. For nPCR, the usage of a new thermostable DNA polymerase facilitated pre-PCR decontamination using uracil-N-glycosylase and “hot start” in single step procedure. The results of the study indicated that DNA amplification assays, either manual or automated, were rapid and specific tools for diagnosing pulmonary tuberculosis.
Angiotensin Converting Enzyme Gene Polymorphism in Coronary Artery Disease: The Indian Scenario
Authors: Joseph Ansamma , Nair Kappiareth Gopal , Ashavaid Tester Framroze
Published: October 2004

Angiotensin converting enzyme is a key component of the renin angiotensin system that plays an important role in cardiovascular regulation. It seems to modulate cardiovascular growth by virtue of its role in the conversion of angiotensin I to angiotensin II and degradation of kinins. A deletion polymorphism localized in intron 16 of the human angiotensin converting enzyme gene, corresponding to a 287 bp long Alu repetitive sequence, was found to be associated with increased risk of myocardial infarction in various subgroups, including European, French and Japanese coronary patients. This angiotensin converting enzyme gene I/D polymorphism was examined by the polymerase chain reaction in a cross-sectional study of 201 healthy Indian subjects and 150 patients (angiographically proven cases of coronary artery disease) whose serum angiotensin converting enzyme levels were concomitantly measured. The D/D, I/D and I/I genotypes were found in 20.66 %, 46.66 % and 32.66 % of the Indian coronary heart disease patients and in 23.38 %, 49.75% and 26.86 % of controls respectively. One of the reasons for not finding an association between the D allele and coronary artery disease in this study could be the ethnic heterogeneity and disease status heterogeneity among the patients and controls. However the phenotypic variance of serum angiotensin converting enzyme levels is strongly influenced by this polymorphism. In the Indian population, the angiotensin converting enzyme gene I/D polymorphism is not associated with risk for coronary artery disease although it is associated with plasma angiotensin converting enzyme activity. Hence the angiotensin converting enzyme gene I/D polymorphism does not seem to be a useful marker for coronary artery disease in the Indian population.
Mutation C677T of Methylenetetrahydrofolate Reductase Gene Is Not Associated with Coronary Artery Disease, but Possibly with Albuminuria, in Type 2 Diabetic Patients
Authors: Wirta Valtteri , Huang Xiao-Hong , Wirta Ole , Rantalaiho Vappu , Pasternack Amos , Jokela Hannu , Koivula Timo , Lehtimäki Terho
Published: October 2004

The missense mutation in the 677th nucleotide (C677T) of methylenetetrahydrofolate reductase gene causes substitution of valine (V) for alanine (A) resulting in three genotypes VV, VA and AA. The VV genotype causes hyperhomocysteinemia and may be a risk factor for coronary artery disease. We determined genotypes by polymerase chain reaction and subsequent restriction fragment length analysis and compared them in 84 patients with type 2 diabetes and in 115 non-diabetic subjects with and without coronary disease. Fractional urinary excretion rate of albumin was assessed by nephelometry. The VV, VA, and AA frequencies in the diabetic and in the control groups were 0.095, 0.357, 0.548 and 0.061, 0.417, 0.522, respectively (p = NS, diabetic vs. controls, χ2 test). Genotype frequencies did not differ in either diabetic or control subjects between those with or those without coronary disease (χ2 test). The fractional urinary excretion rate of albumin (mean ±SD) in diabetic patients with the VV genotype i.e. 1.59 ± 0.71 was lower (Kruskall-Wallis test p = 0.002) than in the other genotypes i.e. VA 5.98 ± 9.75 and AA 3.75 ± 4.77, respectively (post-hoc Mann-Whitney test VV vs. VA p = 0.005 and VV vs. AA p = 0.054, respectively). We found that in patients with type 2 diabetes the methylenetetrahydrofolate reductase VV genotype was associated with a low urinary albumin excretion but not with coronary artery disease or diabetes per se.
Analysis of Clonality in T-Lymphoproliferative Diseases by Multiplex PCR
Authors: Zadro Renata , Sučić Mirna , Aurer Igor , Metelko-Kovačević Jasminka , Labar Boris , Stavljenić Rukavina Ana
Published: October 2004

Distinction between benign and malignant T-cell lymphoproliferative diseases can be difficult using morphological criteria. Using multiplex polymerase chain reaction system we have tested a series of patients with various lymphoproliferative disorders to detect clonal T-lymphocyte populations.

Results show that clonal amplification products were obtained from all 10 patients with T-cell lymphoproliferative disorders while the amplification of DNA samples from B-cell neoplasms and normal individuals revealed polyclonal amplification products.

By splitting the multiplex primer mix, the patient specific T-cell receptor γ rearrangement was determined: five out of ten patients showed the exclusive presence of a single T-cell receptor γ gene rearrangement. Three patients exhibited two rearranged T-cell receptor γ genes, while in two patients positive reactions were obtained with three pairs of primers for variable and joining segments.

Molecular analysis of rearranged T-cell receptor genes by multiplex polymerase chain reaction represents a useful and rapid tool for confirming diagnosis, to determine the extent of disease and to monitor the response to therapy.
The Impact of Molecular Diagnosis on Familial Colorectal Cancer
Authors: Bennett Graeme , Rudzki Zbigniew , Cole Steve , Young Graeme , Suthers Graeme
Published: October 2004

We have shown the impact of molecular diagnostics related to mutation detection in an extensive family with a strong history of colorectal cancer. The nature and presentation of the cancers suggested that hereditary nonpolyposis colorectal cancer was the most likely cause. The strategies employed have enabled the detection and characterisation of the causative mutation in the proband and predictive testing in the remaining relatives where requested.

Using the chemical cleavage of mismatches technique and direct sequencing, the MSH2 and MLH1 genes of the proband were investigated. A single base substitution, C→T at nucleotide 350, codon 117, of the MLH1 gene was identified. Across the family pedigree at specific points, 22 other relatives have been tested for the mutation by direct DNA sequencing from genomic DNA. Of the total of 23 patients tested to date, 11 have the mutation.

In conjunction with appropriate genetic counselling, this service has clarified the genetic status of many individuals within this family. Predictive information provided prior to the development of symptoms enables individuals to make informed choices regarding disease management and the future, removing the anxiety associated with the unknown.
CGG Repeat Interruptions in the FMR1 Gene in Patients with Infantile Autism
Authors: Poon Priscilla M. K. , Chen Qian L. , Lai Kelly Y. C. , Wong Chung-Kwong , Pang Chi-Pui
Published: October 2004

We determined the CGG repeat length and AGG interruptions in the FMR1 gene in normal Chinese subjects and patients with infantile autism and mild mental retardation. Genomic DNA was investigated by PCR and Southern hybridisation for CGG repeat number and PCR with Mnl I restriction analysis for AGG interruption. Both the normal subjects and the patients with autism have 53 CGG repeats in FMR1, and the majority have two interspersed AGG. Our normal Chinese subjects have a similar number of interspersed AGG as other populations. When compared with the normal subjects, the autism patients have less AGG interruptions and a different pattern of AGG distribution. There was a significant difference in the CGG configurations between normal subjects and patients with autism. The latter had less interspersed AGG, as in fragile X patients, but they did not have fragile X. A study on mentally retarded patients with no infantile autism should also be carried out to ascertain whether mental retardation alone may have contributed to such AGG pattern.
Genetic Basis of Congenital Hypothyroidism: Abnormalities in the TSHβ Gene, the PIT1 Gene, and the NIS Gene
Authors: Tatsumi Ke-ita , Miyai Kiyoshi , Amino Nobuyuki
Published: October 2004

We have elucidated the molecular pathology of three types of congenital hypothyroidism. Thyrotropin (TSH) is the major regulator of thyroid function. In cases of isolated congenital TSH deficiency, we found that they are caused by a missense mutation in the conserved CAGYC region of the TSHβ gene. Pit-1/GHF-1 is a pituitary specific POU-domain DNA binding factor, which transactivates the growth hormone (GH), prolactin (PRL), TSHβ genes, and the PIT1 gene itself. In cases of combined deficiency of GH, PRL, and TSH, we found that they are caused by abnormalities in the PIT1 gene, either recessively or dominantly. Sodium dependent iodide symporter (NIS) actively transports iodide into the thyroid cells to produce thyroid hormones. In cases of iodide transport defect, we elucidated that a missense mutation in the transmembrane region of the NIS gene caused them.
Prostate-Specific Antigen and New Related Markers for Prostate Cancer
Authors: Daher Rose , Beaini Mona
Published: October 2004

Although prostate-specific antigen (PSA), or human kallikrein 3, is the most valuable tool available for the diagnosis and management of prostate cancer, as currently used it is insufficiently sensitive and specific for early detection or staging of the malignancy. Many new concepts have been introduced in order to optimize the clinical use of PSA measurements, but each one has its own drawbacks. The molecular forms of PSA, especially the free PSA, seem to be useful for the detection of prostate cancer in men with PSA concentrations falling in the 4–10 μg/l range. New molecular techniques, such as reverse transcriptase polymerase chain reaction for the detection of minimal amounts of PSA messenger RNA and prostate-specific membrane antigen, offer new promise for the prognosis and possibly staging of prostate cancer. On the other hand, human kallikrein 2, a serine protease closely related to PSA that is also expressed predominantly in the prostate, may be a new adjuvant marker for prostate cancer. As for its biological functions, PSA can no longer be regarded as a specific prostate molecule associated mainly with semen liquefaction when it has a possible role as a prognostic indicator in female breast cancer. The biological role of PSA in normal tissues and tumors may be much more complex than previously thought and requires further investigation.
Haunting Secrets: Tracey Moffatt's beDevil
Authors: Summerhayes Catherine
Published: October 2004

Abstract In her vividly textured, complicated, and passionate film, beDevil, Australian Aboriginal artist and filmmaker Tracey Moffatt avoids easy stereotypes of victims and oppressors. She not only inspects some of the repressed stories of indigenous Australians, but also looks at the bewildered, bedeviled ways in which non-indigenous and indigenous Australians live with each other. Moffatt draws on all aspects of her artistic practice in this feature-length film.
Stigmatizing Substance Use Terminology in Grant Abstracts Following High-Level Language Guidance
Authors: Eschliman Evan L. , Kokaze Haruka , Huang Long Jie , Choe Karen , Mauro Pia M.
Published: February 2025

This cross-sectional study examines the use of stigmatizing terms in US grants funded by the National Institute on Drug Abuse following changes to official guidance on the language of substance use disorders in 2017 and 2021.
Anisotropic Single‐layer Graphene/Nanodiamond Loaded PCL Conduits Provide Biophysical Cues to Manipulate Nerve Biomechanics and Bioelectric Function in the Restoration of Nerve Microenvironment
Authors: Zhan Lei , Wang Xu , Lv Yaowei , Deng Jixia , Nan Liping , Ke Qinfei , Guan Shibing , Huang Chen , Ouyang Yuanming
Published: February 2025

Impaired peripheral nerves are characterized by a disturbed nerve microenvironment where nerve mechanics and physiology are disrupted. Adequate biophysical cues on nerve scaffolds that resemble the mechanical and bioelectrical microenvironments represent an advanced technique for the realization of desirable neural interfaces. Considering that Schwann cells and axons are surrounded by a unique mechanical microenvironment and the electrically sensitive nature of peripheral nerve, a novel neural device is designed by incorporating single‐layer graphene (SLG) and nanodiamond (ND) into nanogrooved polycaprolactone (PCL) fibers. The combination of these nanomaterials with the anisotropic topography (formed by the nanogrooves on surfaces of PCL fiber and the micrometer gaps between neighboring fibers) from fibrous conduit shows extraordinary synergy in enhancing the nerve regeneration process. The SLG/ND/PCL nerve guidance conduit (NGC) successfully triggers the myelinating capacity of Schwann cells via Piezo1 signaling and further enables the concurrent activation of NFAT and Krox‐20 molecule. Cells on the scaffold also present higher mechano‐sensitivity, with the simultaneous suppression of fibrotic activity and the collagen production of fibroblasts. Taken together, the concept of combining nanomaterials with anisotropic topography can enable the myelinating capacity of Schwann cells, thus offering a platform strategy toward the fabrication of a desirable microenvironment for peripheral nerve regeneration.
High‐Load Shape Memory Microgripper with Embedded Resistive Heating and Magnetic Actuation
Authors: Wu Sizhu , Liu Yifan , Zhang Yachao , Zeng Lu , Fang Jinpeng , Chen Chao , Zhang Chenchu , Wu Dong , Lao Zhaoxin , Xia Haojie
Published: February 2025

Magnetically actuated soft grippers find extensive applications in robotics due to their rapid response, biological safety, and wireless control capabilities. However, these systems often require a continuously applied magnetic field during both the capture and release processes, which reduces load capacity and makes gripping ferromagnetic objects challenging. Here, an electrothermal‐magnetic actuated shape memory (EM‐SMP) microgripper is developed. By incorporating Fe₃O₄ particles into the shape memory polymer (SMP) and embedding resistive wires, the microgripper can respond to both electric current and magnetic field. The high thermal conductivity of the composite material, coupled with microscale dimensions achieved via femtosecond laser processing, significantly enhances the response speed (≈0.9 s). The magnetic field is applied only to open the gripper, while closure is realized through the electrothermal‐triggered shape memory effect, allowing sequential closure to safely grip delicate soft objects and magnetic objects without magnetic interference. Upon cooling, the closed state of the SMP gripper locks in place without energy consumption. Furthermore, the claw‐shaped design allows the gripper to enclose larger objects during grasping, thereby improving the load‐to‐weight ratio (≈2380). This gripper demonstrates broad application potential, effectively performing grasp and release tasks across diverse materials, sizes, shapes, states, and extreme environmental conditions (acidic and alkaline).
Designing Confined Thermal‐Recognized Hydrogen Bonding Nanochannels for Effective and Energy‐Efficient Water Isotopologue Sieving
Authors: Wen Rou‐Ming , Ye Hao , Wu Ming‐Bang , Luo Qiao , Ye Qi‐Hui , Hu Zhang‐Ting , Yu Yucong , Yao Juming , Zhang Chao
Published: February 2025

Water isotopologue sieving has been flagged as one of the biggest challenges in modern separation technologies owing to their extremely similar physicochemical properties. As a benchmark candidate, current membrane separation suffers from inferior water isotopologue sieving as imposed by the failure of the size exclusion in conventional membrane separation. Herein, a facile approach is presented to elaborate MXene/Cellulose nanofiber (CNF) membranes featuring confined thermal‐recognized hydrogen bonding nanochannels, enabling highly‐selective, energy‐efficient and durable deuterium water sieving under low‐grade heat. The key to such membranes lies in the meticulous utilization of CNF‐enabled rich thermal‐recognized hydrogen bonds within nanochannels, which attract more deuterium water and water via deuterium bond and hydrogen bond (─OD/─OH) meanwhile thermally recognizing deuterium water with stable ─OD interaction to create more significant diffusion kinetic differences over water under low‐grade heat. It is demonstrated that the MXene/CNF membranes deliver an extraordinary separation factor as high as 5.2 yet demanding energy consumption as low as 2.9 GJ kg−1, outperforming most of state‐of‐the‐art separation technologies. Moreover, the MXene/CNF membrane exhibits stable separation performance under long‐term operations and can be further integrated into multi‐stage separation device for augmenting separation and concentration of deuterium water, making it a step closer to the practical applications.
Enhanced Interfacial Polarization Loss of FeS/MoS2@N‐Doped Carbon Sandwich‐Walled Nanotubes Enables High‐Performance Electromagnetic Wave Absorption
Authors: Shen Yu , Ma Ziqian , Yan Feng , Zhu Chunling , Zhang Xitian , Chen Yujin
Published: February 2025

Multiple interfaces and hollow structures are vital to high‐performance electromagnetic wave (EMW) absorption of absorbers. However, it remains difficult to construct and tune such structures, and there is limited understanding regarding the relationships between their structural and dielectric loss properties. Herein, the theoretical simulations for the EMW absorption performance of the hollow sandwich and solid double‐layer structures are first carried out and it is found that the former exhibits a more pronounced power loss density than the latter. Then, a ligand‐exchange strategy following a vulcanization process to fabricate FeS/MoS2@N‐doped carbon sandwich‐walled nanotubes (FeMoS‐SWCNTs) is dveloped. The experimental results demonstrate that the FeMoS‐SWCNTs show significantly enhanced EMW absorption performance compared to the solid FeS counterparts, consistent with the simulation results. Further density functional theory calculations reveal that the enhanced dielectric properties of FeMoS‐SWCNTs are attributed to a stronger interfacial polarization resulting from electronic interactions at multiple interfaces (FeS/N‐doped carbon (NC), MoS2/NC, and FeS/MoS2), and enhanced conduction loss caused by higher density of states in the FeS/MoS2 heterostructure. These findings elucidate the relationship between the sandwich‐walled nanotube structures and their dielectric loss properties, and the developed method offers a feasible approach for the rational design of sandwich‐walled nanotubes for high‐performance EMW absorption applications.
Thick Hydrogel Membrane With Macro‐Channel for Rapid Uranium Extraction From Seawater
Authors: Zhou Guanbing , Chen Jianming , Gao Feng , Wang Hui , Yuan Yihui , Wang Ning
Published: February 2025

The growing demand for uranium driven by nuclear power development necessitates the creation of macroscale, cost‐effective, and efficient adsorbents for uranium extraction from seawater, a challenge yet to be fully addressed. Amidoxime‐based hydrogel adsorbents are promising candidates but suffer from performance limitations due to bound water obstructing pore channels and impeding uranyl ion migration. Herein, a thick macro‐channel poly(amidoxime)‐polyvinyl alcohol hydrogel membrane (MCHM) with a double cross‐linking structure is introduced, designed to enhance uranium adsorption. Unlike traditional powders and microfibers, the macroscale thick membrane facilitates deployment and recovery in marine environments, while its directional channel structure improves mass transfer properties and accessibility to amidoxime groups. Using COMSOL Multiphysics, design parameters such as channel size, membrane thickness, and arrangement are optimized, significantly enhancing performance while reducing costs. In natural seawater, the optimized MCHM with 2.0 mm channels, 20 times thicker than ultra‐thin hydrogel membranes demonstrated improvements of 99% in adsorption capacity and 179% in adsorption rate compared to non‐channel counterparts. This method uniquely combines material innovation with computational modeling, providing valuable insights into how the internal channel structure of adsorbents influences their performance. The findings provide a scalable design solution for hydrogel adsorbents, enabling sustainable uranium extraction from seawater.
A Library of Polyphenol‐Amino Acid Condensates for High‐Throughput Continuous Flow Production of Nanomedicines with Ultra‐High Drug Loading
Authors: Yi Zeng , Ma Xiaomin , Tong Qiulan , Ma Lei , Tan Yunfei , Liu Danni , Tan Chaoliang , Chen Junze , Li Xudong
Published: February 2025

Synthesizing high drug‐loading nanomedicines remains a formidable challenge, and achieving universally applicable, continuous, large‐scale engineered production of such nanomedicines presents even greater difficulties. This study presents a scalable library of polyphenol‐amino acid condensates. By selecting amino acids, the library enables precise customization of key properties, such as carrier capacity, bioactivity, and other critical attributes, offering a versatile range of options for various application scenarios. Leveraging the properties of solvent‐mediated disassembly and reassembly of condensates achieved an ultra‐high drug loading of 86% for paclitaxel. For a range of poorly soluble molecules, the drug loading capacity exceeded 50%, indicating broad applicability. Furthermore, employing a continuous microfluidic device, the production rate can reach 5 mL min−1 (36 g per day), with the nanoparticle size precisely tunable and a polydispersity index (PDI) below 0.2. The polyphenol‐based carrier demonstrates efficient cellular uptake and, in three distinct animal models, has been shown to enhance the therapeutic efficacy of paclitaxel without significant side effects. This study presents a streamlined, efficient, and scalable approach using microfluidics to produce nanomedicines with ultra‐high drug loading, offering a promising strategy for the nanoformulation of poorly soluble drugs.