bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of diabetes on plasma nitrotyrosine levels
Authors: Wang X. L. , Rainwater D. L. , Leone A. , Mahaney M. C.
Published: May 2004

Background  Oxidative stress plays a major role in disease processes such as atherosclerosis and diabetes. Peroxynitrite is a reaction product of nitric oxide (NO) and superoxide and a potent oxidant. The peroxynitrite‐mediated tyrosine nitration, which forms nitrotyrosine (NT), is associated with several pathological conditions.

Methods  We measured plasma NT levels using the HPLC method in 40 Mexican Americans with diabetes, but not taking medications, and 40 age‐ and sex‐matched euglycaemic controls.

Results  Plasma‐free NT levels were not different between subjects with diabetes (11.0 ± 1.7 nmol/l, n = 40) and with non‐diabetes (10.4 ± 1.5 nmol/l, n = 40). There was also no association with levels of fasting glucose (r = −0.049, P = 0.663) or 2‐h glucose (r = −0.099, P = 0.390). However, females had significantly lower free NT level (7.6 ± 1.4 nmol/l, n = 40) than males (13.8 ± 1.7 nmol/l, n = 40, P = 0.005), which were not affected by age, smoking status, BMI and glucose levels.

Conclusions  In contrast to some earlier reports, our study shows that diabetes has no effect on plasma NT levels in Mexican Americans. We have also demonstrated lower free NT levels in females than males, which may partly explain the lower risk profile to vascular disease in women.
Strong association of C‐reactive protein with body mass index and 2‐h post‐challenge glucose in non‐diabetic, non‐smoker subjects without hypertension
Authors: Hashimoto K. , Kasayama S. , Yamamoto H. , Kurebayashi S. , Kawase I. , Koga M.
Published: May 2004

Aims  Increases in C‐reactive protein (CRP) levels have been shown to be associated with cardiovascular diseases as well as asymptomatic atherosclerosis and to be closely related to traditional cardiovascular risk factors. The aim of this study was to determine the clinical and biochemical characteristics associated with CRP in non‐diabetic, non‐smoker subjects without hypertension.

Methods  A 75‐g oral glucose tolerance test was performed on 305 Japanese subjects aged 40–70 years who were undergoing health examinations. We recruited non‐diabetic, non‐smoker subjects without hypertension. Subjects with known cardiovascular diseases, chronic or acute inflammation, malignant diseases, or autoimmune disorders were excluded. Plasma high‐sensitivity CRP was measured in 125 subjects who satisfied the admission criteria.

Results  Plasma CRP levels were significantly higher in the 28 subjects with impaired glucose tolerance (IGT) than that in the 97 subjects with normal glucose tolerance (NGT) (median 0.53, range 0.18–1.10 mg/l vs. median 0.32, range 0.17–0.49 mg/l; P = 0.032). There was a positive correlation of CRP with body mass index (BMI), triglycerides, uric acid, fasting glucose, oral glucose tolerance test (OGTT) 1‐h glucose, OGTT 2‐h glucose, and a negative correlation with HDL cholesterol. Multivariate regression analysis identified BMI (F = 8.57, P = 0.004) and OGTT 2‐h glucose (F = 5.96, P = 0.016) as independent predictors for CRP.

Conclusions  BMI and OGTT 2‐h glucose are the most important predictors for plasma CRP in non‐diabetic, non‐smoker subjects without hypertension.
Integrons and multidrug resistance among Escherichia coli causing community‐acquired urinary tract infection in southern India
Authors: MATHAI ELIZABETH , GRAPE MALIN , KRONVALL GÖRAN
Published: May 2004

Antimicrobial resistance genes are often clustered in integrons, genetic elements capable of recombination. There is a paucity of data on the prevalence and role of integrons from community‐acquired infections in developing countries where resistance to co‐trimoxazole is high. We determined the prevalence of integrons among Escherichia coli causing community‐acquired urinary tract infection (UTI). Consecutive isolates of E. coli obtained from UTI of pregnant women at the Christian Medical College Hospital, Vellore, India, during 2002 were included. All isolates were tested for susceptibility to 16 antimicrobials using the disc diffusion method and for integrons of classes 1 and 2 by PCR. Of the 58 isolates tested, 28 (48.3%) were resistant to co‐trimoxazole and trimethoprim. All these isolates carried integrons. Three additional isolates were sulfonamide resistant but integron negative. Class 1 integrons were present in 21 (36.2%) isolates. Resistance to ampicillin (p=0.000), nalidixic acid (p=0.001), chloramphenicol (p=0.02), tetracycline (p=0.004) and gentamicin (p=0.02) was significantly more common in isolates with integrons. DNA sequencing of two isolates with integrons showed the presence of aadA, dfr1 and dfr7 genes. This study demonstrated that integrons are widely prevalent in India and that they might play a role in multidrug resistance in E. coli from community‐aquired UTI.
Geographically dependent distribution of gyrA gene mutations at codons 83 and 87 in Salmonella Hadar, and a novel codon 81 Gly to His mutation in Salmonella Enteritidis
Authors: LINDSTEDT B. A. , AAS L. , KAPPERUD G.
Published: May 2004

In all, 90 nalidixic acid‐resistant clinical strains of Salmonella Hadar and Salmonella Enteritidis isolated in Norway but of predominantly foreign origin were subjected to sequencing of the gyrA, gyrB, parC and parE genes. All the isolates contained at least one mutation in gyrA codon 83 or codon 87. A highly significant correlation between mutations in gyrA codon 83 and strains originating from Southeast Asia was found in S. Hadar but not in S. Enteritidis. A novel gyrA codon 81 Gly to His mutation was discovered in one S. Enteritidis isolate. One amino‐acid (aa) changing mutation was found outside the quinolone resistance‐determining region (QRDR) of S. Hadar parC at codon 57, which has previously only been observed once in Salmonellae.
Relationship between area deprivation and the anticaries benefit of an oral health programme providing free fluoride toothpaste to young children
Authors: Ellwood R. P. , Davies G. M. , Worthington H. V. , Blinkhorn A. S. , Taylor G. O. , Davies R. M.
Published: May 2004

Abstract – Objective: To determine the effectiveness of providing free toothpaste containing either 1450 or 440 ppm F on caries experience in 5‐year‐old children living in areas with different levels of material deprivation.Design:  Five‐year, examiner‐blind, randomized, controlled, parallel‐group, clinical trial. Children were randomly assigned to three groups.Setting:  Health Districts in the north‐west of England with high levels of dental caries. Clinical examinations were performed in schools during the period October 1999 to April 2000 when the children were 5–6 years old.Participants:  Children from 3‐month birth cohorts resident in nine, nonfluoridated health districts.Interventions:  Toothpaste containing either 440 or 1450 ppm F and dental health literature posted at 3‐month intervals and toothbrush provided annually from the age of 1–5 years. Comparison group received no intervention.Main outcome measures:  Mean dmft and proportion of participants with dmft > 0, dmft ≥ 4, upper primary incisor caries and extraction of one or more primary teeth. Outcomes tabulated for quartiles of participants based on the distribution of the Townsend index of material deprivation.Results:  A total of 3467 children were included in the final data analysis. The Townsend index was found to be useful in identifying groups of children with increased caries risk. Overall, participants in the programme using the high‐fluoride toothpaste had significantly (P < 0.002) less caries than the comparison group with similar absolute reductions in mean dmft for the most‐ and least‐deprived groups. Relative to the comparison group the association between deprivation and dental caries was changed so that in the most‐deprived quartile those using the low‐fluoride toothpaste tended to have less dental caries than the comparison group whereas in the least deprived they tended to have more. This difference in the association (slope) was statistically significant (P < 0.05). Provision of both low‐ and high‐fluoride toothpaste appeared to reduce the risk of extractions for participants in the most‐deprived quartile (P < 0.05).Conclusion:  The relative benefits of the programmes supplying the two toothpastes considered in this study are different depending on the deprivation status of the participants. For the most‐deprived groups postal provision of either a low‐ or high‐fluoride toothpaste provides similar levels of benefit. In the less deprived groups only provision of the high‐fluoride toothpaste provided a benefit. The absolute caries reduction seen for provision of the high‐fluoride toothpaste was not related to the deprivation status and hence the programme did not reduce deprivation‐related health inequalities. Targeting the programme using the methods employed in this study is unlikely to improve the effectiveness of the programme.
The effectiveness of a 6‐year oral health education programme for primary schoolchildren
Authors: Vanobbergen Jacques , Declerck Dominique , Mwalili Samuel , Martens Luc
Published: May 2004

Abstract –  Objectives: The aim of this study was to evaluate the effect of a 6‐year oral health education programme in primary schoolchildren. Methods: This programme was part of the Signal‐Tandmobiel® project, a longitudinal collaborative project combining the registration of oral health data and oral health promotion. The intervention group comprised 3291 children with a mean age of 7.1 years (SD 0.43) at the start of the programme. Every year these children were examined clinically and a questionnaire, to be filled in by the parents, was administered to assess oral health behaviour. These children received an oral health education programme which consisted of a yearly 1‐h instruction. Data collected using the same questionnaire and clinical examination in 676 12‐year‐old children were included as control group. The samples were obtained using stratified cluster sampling. The effect of the interventional programme was assessed by measuring differences in caries prevalence and incidence, levels of dental care and reported oral health behaviour. Results: Mean DMFT/S values, although higher in the control group, were not significantly different. The reported frequency of brushing was the same in both groups. Significant differences in favour of the intervention group were found in the number of between‐meal snacks (P < 0.001) and the proper use of topical fluorides (P < 0.05). Children in the control group showed a significantly lower proportion of filled teeth than those in the intervention group (P < 0.01), with a care index of 73% versus 80%.Conclusion: In conclusion, the implemented minimal school‐based oral health education programme did not result in a significant reduction of the caries prevalence measured. The programme has been effective in improving reported dietary habits and the proper use of topical fluorides and resulted in a higher care index.
Determining the optimal concentration of fluoride in drinking water in Pakistan
Authors: Khan Ayyaz Ali , Whelton Helen , O'Mullane Denis
Published: May 2004

Abstract –  Objectives: This study was designed to determine the optimal concentrations of fluoride for drinking water in Pakistan. Clinical dental examination of 1020 school children aged 12 years was carried out in 19 cities of Pakistan. Correlation between concentrations of water fluoride, caries and fluorosis was investigated by analyzing the data on fluoride concentrations in drinking water in the sampled population for which the caries and the fluorosis levels were also measured. Methods: The optimal level of fluoride in drinking water is universally calculated by applying the equation of Galagan and Vermillion, which permits the calculation of water intake as a function of temperature. The annual mean maximum temperatures (AMMT) recorded during the last 5 years were collected from the meteorological centres of the 28 divisional headquarter stations. The average AMMT of Pakistan is 29°C at which the optimal fluoride in drinking water of Pakistan was calculated to be 0.7 ppm. As drinking habits differ in various parts of the world, determination of optimal concentration of fluoride for drinking water in Pakistan was performed using a modified Galagan and Vermillion equation, which applies a correction factor of 0.56 to the equation. The optimal fluoride in drinking water in Pakistan using this modified equation was determined to be 0.39 ppm. Results: Observation of the correlation showed that a fluoride concentration of 0.35 ppm in drinking water was associated with maximum reduction in dental caries and a 10% prevalence of fluorosis. Conclusions: Determining the most appropriate concentrations of fluoride in drinking water is crucial for communities. It is imperative that each country calculates its own optimal level of fluoride in drinking water based on the dose–response relationship of fluoride in drinking water with the levels of caries and fluorosis. Climatic conditions, dietary habits of the population and other possible fluoride exposures need to be considered in formulating these recommendations.
The effect of pre‐operative information in relieving anxiety in oral surgery patients
Authors: Ng Sam K. S. , Chau Albert W. L. , Leung W. Keung
Published: May 2004

Abstract – Appropriate stress management of patients is essential for smooth running of invasive or surgical dental procedures conducted under local anaesthesia.Objective: The current study analysed the effectiveness of pre‐operative information provision for anxiety reduction during dentoalveolar surgery in patients with high‐ or low‐trait anxiety.Methods: Patients scheduled for oral surgical procedures performed by six private dental practitioners were invited to participate in the study. They were randomly assigned to four groups and received the following pre‐operative information: (i) basic information only, (ii) basic information with details of the operative procedures, (iii) basic information with details of the expected recovery, and (iv) basic information with details of both the operative procedures and recovery. The participants’ trait anxiety level was measured with the Depression Anxiety Stress Scales (DASS), then they were divided into high‐ or low‐trait anxiety groups with the method of median‐split on the basis of the DASS score. Self‐rated anxiety was recorded immediately before, during and 10 min after the surgical procedures.Results: High‐trait anxiety subjects gave higher self‐reported anxiety levels (repeated‐measures ANOVA,P < 0.05). Pre‐operative provision of details about the expected recovery only or details concerning both the operative procedures and recovery led to significant reduction in self‐reported anxiety among the participants throughout the procedure (P < 0.01). However, information on operative procedures led to anxiety reduction in low (P < 0.05) but not high‐trait anxiety participants.Conclusion: Provision of pre‐operative information of the recovery process leads to significant anxiety reduction in all patients who undergo surgical/invasive procedures with local anaesthesia.
EXCHANGE–CORRELATION KERNEL IN TIME-DEPENDENT DENSITY FUNCTIONAL THEORY DERIVED FROM MANY-BODY THEORY
Authors: KARLSSON K. , ARYASETIAWAN F.
Published: May 2004

We derive a simplified Bethe–Salpeter equation for calculating optical absorption based on the assumption of a local electron–hole interaction. The original four-point equation for the kernel is reduced to a two-point one. A connection to the exchange–correlation kernel in time-dependent density functional theory can be established. The resulting fxc is found to be -W/2 where W contains only the short-range (local) part of the Coulomb screened interaction. This simple approximation was successfully applied to optical absorption spectra of some excitonic crystals, reproducing not only the continuum excitons but also the bound ones.
BOSE–EINSTEIN CONDENSATES WITH LASER-INDUCED DIPOLE–DIPOLE INTERACTIONS BEYOND THE MEAN-FIELD APPROACH
Authors: KURIZKI G. , MAZETS I. E. , O'DELL D. H. J. , SCHLEICH W. P.
Published: May 2004

We present a brief review of our recent results concerning non-mean-field effects of laser-induced dipole–dipole interactions on static and dynamical properties of atomic Bose–Einstein condensates.
BURNSIDE AND KUROSH PROBLEMS
Authors: HAMMOUDI LAKHDAR
Published: May 2004

For any integer d≥2 and over any field [Formula: see text], we construct a residually finite nonnilpotent nil algebra over [Formula: see text] generated by d elements such that any d-1 elements generate a nilpotent subalgebra. This leads to analogous results for nonassociative algebras and groups. In our proof we do not use the well-known Golod-Šafareviš lemma.
COMPUTING 2 NORM OF TRANSFER FUNCTIONAL SPACE OF THE CALCIUM ION GATING CHANNEL SYSTEM BY THE H2 CONTROL PRINCIPLE
Authors: HIROHUMI HIRAYAMA
Published: May 2004

We propose the H 2 control principle to evaluate the calcium ion channel gating function by allosteric modeling. Calcium ion channel was described by four sub-units — four voltage sensitive S4 molecules allosteric modeling. The allosteric properties were characterized by cooperative positional changes of voltage sensitive S4 molecule in each of the sub-unit and concerted conformational changes of all the sub-units. We applied the H 2 control strategy for minimizing the influence of noise on the output of the channel system. The allosteric cooperative behavior of four S4 molecules and concerted channel opening were expressed by allosteric parameter fn where n indicates number of activated voltage sensor in one channel molecule. The channel states were associated to ten which are composed of each five for closed and open states characterized by one to four of active positioned voltage sensor molecules S4. The temporal changes in amount of channel species were described by ten differential equations. By applying the H 2 control principle, a set of differential equations that minimize the influence of noise on the output were obtained in combination with related Riccati equations for the system state and system observers. The potency of minimizing the control input for state transitions was measured by the weighting coefficients timed by that control input. The influence of noise on the system was measured by computing 2 norm of the transfer function from noise to output under H 2 principle.

Increases in weighting coefficients of control input for the cooperative activation process of open channel states and concerted opening process reduced the magnitude of 2 norm of the transfer function from noise to output of the system. The 2 norm decreased as allosteric parameter f decreased when one voltage sensor was activated while the 2 norm decreased as f increased when four voltage sensors here activated. The influence of changes in f was contrasted between closed states and open states. The present work will be available for measuring the influence of noise on the ion channel.
WAVELET-BASED MEDICAL IMAGE COMPRESSION USING EZW: OBJECTIVE AND SUBJECTIVE EVALUATIONS
Authors: LOW YIN FEN , BESAR ROSLI
Published: May 2004

Recently, the wavelet transform has emerged as a cutting edge technology within the field of image compression research. Wavelet methods involve overlapping transforms with varying-length basis functions. This overlapping nature of the transform alleviates blocking artifacts, while the multi-resolution character of the wavelet decomposition leads to superior energy compaction and perceptual quality of the decompressed image. Embedded zerotree wavelet (EZW) coder is the first algorithm to show the full power of wavelet-based image compression. The main purpose of this paper is to investigate the impact and quality of orthogonal wavelet filter in compressing medical image by using EZW. Meanwhile, we also look into the effect of the level of wavelet decomposition towards compression efficiency. The wavelet filters used are Haar and Daubechies. The compression simulations are done on three modalities of medical images. The objective (based on PSNR) and subjective (perceived image quality) results of these simulations are presented.
ESTIMATION OF LOW BONE MASS FOR THE ASSESSMENT OF OSTEOPOROSIS FRACTURE RISK IN INDIAN MEN AND WOMEN USING QUANTITATIVE ULTRASOUND AND DUAL ENERGY X-RAY ABSORPTIOMETRY
Authors: HOLI MALLIKARJUN S. , RADHAKRISHNAN S.
Published: May 2004

The objective of the present work is to estimate the prevalence of low bone mass in Indian men and women for the assessment of osteoporosis and fracture risk using quantitative ultrasound and dual energy X-ray absorptiometry (DEXA) and carryout a comparative evaluation for early prediction of osteoporosis. Data collected in this study is analyzed to assess the diagnostic performance of the ultrasound and how its performance compares to DEXA bone mineral density (BMD). Quantitative ultrasound assessment of osteoporosis is carried out by measuring broadband ultrasound attenuation (BUA) and speed of sound (SOS) through calcaneus bone to provide a clinical measure called the stiffness index (SI). The SI is a measure of bone density used to predict the risk of bone fracture due to osteoporosis. Bone mineral density (BMD) measurement is performed in lumbar region (L1–L4) of the spine in anterior-posterior direction using DEXA. In both studies the data is found to be significant in men and women subjects with p<0.0005 and percentage bone loss in men and women are significantly matching in both studies. Ultrasound performance correlates moderately well with DEXA (r=0.60 to 0.68) and provides comparable diagnostic sensitivity to spine BMD in predicting osteoporotic fractures.
SPATIAL AND MECHANOEMISSION CHAOS OF MECHANICALLY DEFORMED TUMOR CELLS
Authors: OREL VALERIY E. , DZYATKOVSKAYA NATALIYA N. , DANKO MICHAIL I. , ROMANOV ANDRIY V. , MEL'NIK YURI I. , GRINEVICH YURI A. , MARTYNENKO SVETLANA V.
Published: May 2004

The development and spreading of tumor process is accompanied by changes in nonlinear (chaotic) dynamics of mechanochemical interaction process in the group of cells. Taking into consideration spatial irregularity and heterogeneity of internal structures of tumor cells, we suggested that treatment by mechanically deformed (MD) syngeneic tumor cells (STC) would be accompanied by changed influence on malignant growth. The objective of this work was to compare spatial, mechanoemission (ME) chaos of MD STC of carcinoma Lewis and melanoma B16 and their malignant growth. MD STC preparation included the aseptic removal of the animal tumor, lyophilization and next mechanical deformation in the microvibratory mill. The suspension of non-deformed or MD STC was injected intraperitoneally. Morphological, morphometric and mechanoemission studies used for estimate of spatial chaos and heterogeneity structure in tumor cells and blood. For Lewis carcinoma the reduction of spatial and ME chaos of cells is accompanied by regression in tumor growth and metastasis. For melanoma B16 the decrease of spatial chaos and the increase of ME chaos in cells is accompanied by initiation of tumor growth and metastasis. These results illustrated equivalent tendencies in chaos changing in spatial and ME chaos for carcinoma Lewis, while opposite tendencies were observed for melanoma B16. Blood ME of mice with melanoma B16 have greater ME chaos in comparison with animals with Lewis carcinoma. This confirmed that the concept of deterministic chaos is hierarchical for the host during cancer process. Results of comparative analysis between spatial, mechanoemission chaos of MD STC and malignant growth could be useful for gain a better understanding relationship of nonlinear biomechanical processes to tumor cells.
Perinuclear localization of Na-K-Cl-cotransporter protein after human cytomegalovirus infection
Authors: Maglova Lilia M. , Crowe William E. , Russell John M.
Published: May 2004

We ( 41 ) previously reported that Na-K-Cl-cotransporter (NKCC) function and microsomal protein expression are both dramatically reduced late in human cytomegalovirus (HCMV) infection of a human fibroblast cell line (MRC-5). We now report DNA microarray data showing that no significant HCMV-dependent NKCC gene repression can be detected 30 h postexposure (PE) to the virus. Consequently, we used plasma membrane biotinylation and subsequent subcellular fractionation in combination with semiquantitative immunoblotting and confocal microscopy to investigate the possibility that intracellular redistribution of the NKCC protein after HCMV infection could be a cause of the HCMV-induced loss of NKCC ion transport function. Our results show that the lifetime of plasmalemmal NKCC protein in quiescent, uninfected MRC-5 cells is ∼48 h, and <20% of the total expressed NKCC protein are in the plasma membrane. The remainder (∼80%) was detected as diffusely distributed, small punctate structures in the cytoplasm. Following HCMV infection: 1) NKCC protein expression in the plasmalemma was sharply reduced (∼75%) within 24 h PE and thereafter continued to slowly decrease; 2) total cellular NKCC protein content remained unchanged or slightly increased during the course of the viral infection; and 3) HCMV infection caused NKCC protein to accumulate in the perinuclear region late in the HCMV infection (72 h PE). Thus our results imply that, in the process of productive HCMV infection, NKCC protein continues to be synthesized, but, instead of being delivered to the plasma membrane, it is clustered in a large, detergent-soluble perinuclear structure.
Dual effect of insulin-like growth factor on the apical 70-pS K channel in the thick ascending limb of rat kidney
Authors: Wei Yuan , Chen Yu-Jung , Li Dimin , Gu Ruimin , Wang Wen-Hui
Published: May 2004

We used the patch-clamp technique to study the effect of insulin-like growth factor I (IGF-I) on the apical 70-pS K channel in the isolated thick ascending limb (TAL) of the rat kidney. The isolated TAL was cut open to gain access to the apical membrane. Addition of 25 nM IGF-I stimulates the apical 70-pS K channel and increases channel activity, defined by the product of channel open probability and channel number, from 0.31 to 1.21. The stimulatory effect of IGF-I is not mediated by nitric oxide- or protein tyrosine phosphatase-dependent mechanisms, because inhibition of nitric oxide synthase or blocking protein tyrosine phosphatase did not abolish the stimulatory effect of IGF-I on the 70-pS K channel. In contrast, inhibition of mitogen-activated protein (MAP) kinase with PD-98059 or U0126 abolished the stimulatory effect of IGF-I. This suggests that MAP kinase is responsible for mediating the effect of IGF-I on the apical K channels. Moreover, the effect of IGF-I on the apical 70-pS K channel is biphasic because high concentrations (>200 nM) inhibit apical 70-pS K channels. Application of 400 nM IGF-I decreased channel activity from 1.45 to 0.2. The inhibitory effect of IGF-I is not blocked by calphostin C (an inhibitor of PKC), but inhibition of protein tyrosine kinase with herbimycin A abolished the IGF-induced inhibition. We conclude that IGF-I has a dual effect on the apical 70-pS K channel in the TAL: low concentrations of IGF-I stimulate, whereas high concentrations inhibit the channel activity. The stimulatory effect of IGF-I is mediated by a MAP kinase-dependent pathway, whereas the inhibitory effect is the result of stimulation of protein tyrosine kinase.
Parkin and relatives: the RBR family of ubiquitin ligases
Authors: Marín Ignacio , Lucas J. Ignasi , Gradilla Ana-Citlali , Ferrús Alberto
Published: May 2004

Mutations in the parkin gene cause autosomal-recessive juvenile parkinsonism. Parkin encodes a ubiquitin-protein ligase characterized by having the RBR domain, composed of two RING fingers plus an IBR/DRIL domain. The RBR family is defined as the group of genes whose products contain an RBR domain. RBR family members exist in all eukaryotic species for which significant sequence data is available, including animals, plants, fungi, and several protists. The integration of comparative genomics with structural and functional data allows us to conclude that RBR proteins have multiple roles, not only in protein quality control mechanisms, but also as indirect regulators of transcription. A recently formulated hypothesis, based on a case of gene fusion, suggested that RBR proteins may be often part of cullin-containing ubiquitin ligase complexes. Recent data on Parkin protein agrees with that hypothesis. We discuss the involvement of RBR proteins in several neurodegenerative diseases and cancer.
A density theorem for locally convex lattices
Authors: Kravvaritis Dimitrie , Păltineanu Gavriil
Published: May 2004

Let E be a real, locally convex, locally solid vector lattice of
(AM)‐type. First, we prove an approximation theorem of
Bishop′s type for a vector subspace of such a lattice. Second,
using this theorem, we obtain a generalization of Nachbin′s
density theorem for weightedspaces.
On a nonlocal Cauchy problem for differential inclusions
Authors: Gatsori E. , Ntouyas S. K. , Sficas Y. G.
Published: May 2004

We establish sufficient conditions for the
existence of solutions for semilinear differential
inclusions, with nonlocal conditions. We rely on a fixed‐point
theorem for contraction multivalued maps due to Covitz and Nadler
andon the Schaefer′s fixed‐point theorem combined with lower
semicontinuous multivalued operators with decomposable values.
Th1/Th2 Paradigm in Pregnancy: Paradigm Lost?
Authors: Chaouat Gérard , Ledée-Bataille Natalie , Dubanchet Sylvie , Zourbas Sandrine , Sandra Olivier , Martal Jacques
Published: May 2004

In this paper, we briefly survey the history of concepts in reproductive immunology from antibody-mediated tolerance to the ‘fetal allograft’ to the current concept of an embryo ‘bathing in a sea of cytokines’. We then review the paradigm that ‘allopregnancy is a Th2 phenomenon’ and some of the evidence gained in animals and humans supporting it. We continue by discussing the light it sheds on immunologically caused recurrent abortion, and the present status of the concepts. We next show the limits of the Th1/Th2 paradigm by reviewing the role of ‘inflammatory’ cytokines in implantation (as first seen with leukemia inhibitory factor). We go on to discuss recent data showing that interferon-γ is not solely a ‘bad guy’, e.g. abortifacient as the paradigm would predict, but is needed at low doses for the vascular development and transformation of uterine spiral arteries required for implantation and successful pregnancy. We conclude by discussing the emerging role of NK and IL-12, IL-15, IL-18 tripods and other cytokines in local angiogenesis and tissue remodelling, a series of new data bringing us well beyond the Th1/Th2 paradigm in pregnancy which, in this context, appears now obsolete and an oversimplification, although it has indeed been useful at first. Rather, step-specific events have to be considered and a key role is seen in local tissue remodelling, in which immune cytokines play an important role while not always being secreted by immune cells.
Phase II Study of Cisplatin and 5-Fluorouracil (PF) and Mitomycin C, Vincristine, Cisplatin and 5-Fluorouracil (MVPF) in Patients with Metastatic Large Bowel Cancer: An Eastern Cooperative Oncology Group Study (EST 1285)
Authors: Pandya Kishan J. , Lefkopoulou Myrto , Petrelli Nicholas J. , Vaughn David J. , Smith Thomas J. , Harris Jules E. , Haller Daniel G.
Published: May 2004

Purpose: To compare the efficacy and the toxicity of cisplatin and 5-fluorouracil (PF) and mitomycin C, vincristine, cisplatin and 5-fluorouracil (MVPF) in patients with metastatic large bowel cancer. Patients and Methods: A total of 94 patients with no prior chemotherapy and measurable metastatic large bowel cancer were randomly assigned to one of the two treatment regimens. Eastern Cooperative Oncology Group (ECOG) criteria were used to evaluate response and toxicity. Results: Fifty patients were randomized to PF and 44 to MVPF. Toxicity was evaluable in all patients except one; response was evaluable in 40 and 31, with response rate of 13 and 42%, respectively. Intent-to-treat analysis showed a response rate of 12 and 32%, respectively (p = 0.076), where it was assumed that none of the ineligible or unevaluable patients responded. Median survival for all patients was 9 months, with no difference between PF and MVPF. ECOG Performance Status (0 vs. 1), weight loss (≤10 vs. >10%) and site of metastatic lesion had statistically significant impact on survival. MVPF was definitely more toxic than PF (p < 0.000005). Conclusion: Both treatment regimens showed clinical activity. The MVPF regimen resulted in more responses than PF, no improvement in survival, and more toxicity.
Serum HCGβ and CA 72-4 Are Stronger Prognostic Factors than CEA, CA 19-9 and CA 242 in Pancreatic Cancer
Authors: Louhimo Johanna , Alfthan Henrik , Stenman Ulf-Håkan , Haglund Caj
Published: May 2004

Objective: In pancreatic cancer, the extent of the spread of the disease is considered to be the strongest prognostic factor. In addition, tumor markers, particularly CA 19-9, may also provide prognostic information. In this study, we evaluated the prognostic value of serum tumor markers CEA, CA 19-9, CA 242, CA 72-4 and hCGβ in pancreatic cancer. Methods: Preoperative serum samples were obtained from 160 patients with pancreatic cancer, including 10 with stage I, 25 with stage II, 24 with stage III and 101 patients with stage IV cancer. Quantitation of CEA, CA 19-9, CA 242, and CA 72-4 in serum was performed with commercial assays. HCGβ was measured with an in-house immunofluorometric assay based on monoclonal antibodies specific for the free β-subunit of hCG. Survival analysis was performed with univariate Kaplan-Meier life-tables and log-rank test, and with multivariate Cox regression analysis. Results: Of the tumor markers studied, CA 19-9 was most frequently elevated. Overall 2-year survival was 10%. Stage, tumor location and size, curative resection, and CEA, CA 72-4 and hCGβ were all found to be prognostic factors (p < 0.026) in univariate analysis. In multivariate analysis, each marker had independent prognostic value (p < 0.011) when analyzed individually but adjusting for stage. When all the covariates were included in the same model, the strongest prognostic factor was hCGβ followed by CA 72-4 and stage. The other clinical characteristics and serum tumor markers contributed insignificant prognostic information. Conclusions: All the tumor markers studied (CEA, CA 19-9, CA 242, CA 72-4, and hCGβ) had prognostic value in pancreatic cancer, and hCGβ, CA 72-4, and stage were the strongest independent prognostic factors in this study.
Efficacy of Treatment with Irinotecan and Oxaliplatin Combination in FU-Resistant Metastatic Colorectal Cancer Patients
Authors: Bajetta Emilio , Beretta Elena , Di Bartolomeo Maria , Cortinovis Diego , Ferrario Erminia , Dognini Giuseppina , Toffolatti Luisa , Buzzoni Roberto
Published: May 2004

Objectives: As single agents, irinotecan and oxaliplatin are active in colorectal cancer after fluorouracil (FU)-containing regimen failure. Their synergistic activity and non-overlapping toxicity profile are well documented, but more data are needed to explore their exact sequence. The aim of this study was to evaluate the activity and tolerability of irinotecan followed by oxaliplatin in patients with FU-resistant colorectal cancer. Methods: FU resistance was defined as disease progression during or within 6 months of discontinuing first-line or adjuvant FU/leucovorin chemotherapy. The study treatment consisted of irinotecan 150 mg/m2 on days 1 and 8 followed by oxaliplatin 85 mg/m2 on day 1 every 3 weeks. In order to improve the safety profile, we changed the schedule during the study to irinotecan 300 mg/m2 on day 1 and oxaliplatin 85 mg/m2 on day 2 every 3 weeks. Results: Of 54 patients treated, the 45 patients with measurable disease were assessed in the efficacy analysis, whereas all patients receiving at least one cycle were evaluated in the safety analysis. Of the patients assessed for efficacy analysis, 19 cases received the first schedule and 26 patients received the second schedule. Twenty-two patients (49%) responded, 10 of the first schedule and 12 of the second schedule group. Stable disease was observed in 35% of all patients. The median response duration was 6.5 months (range 3–10), the median time to progression was 8 months (range 6–10), and the overall survival was 15 months (10–26+). The NCI-CTC grade 3 side effects documented in all of the treated patients were: nausea/vomiting (11%), diarrhea (18%), and neutropenia (7%); grade 4 diarrhea was observed in 2% of patients. Conclusion: The combination of irinotecan followed by oxaliplatin combination is well tolerated and highly active in FU-resistant metastatic colorectal cancer patients.
Canine Long-Term Bone Marrow Culture Neutrophil Production and Functionality
Authors: Fermín M.L. , Gaitán S. , Fragío C. , Léon L.G. , Ostronoff L.K. , Kremmer E. , Kolb H.J. , Tejero C.
Published: May 2004

This in vitro study has been conducted to determine the optimal experimental conditions under which to produce canine neutrophils in long-term bone marrow cultures (LTBMC), establish functional parameters of neutrophils obtained from LTBMC and peripheral blood and to ascertain whether these cells display physiological similarities. Our aim is to provide an experimental model, enabling a correlation between hemopoietic injury and neutrophil functionality. The authors demonstrate for the first time that canine neutrophils grown in cultures are able to produce oxyradicals capable of killing bacterial products. Moreover, culture-grown neutrophils contain gelatinase granules, a marker of terminal neutrophil differentiation, and express a specific surface antigen. The results described in this article illustrate the development of a dynamic system that mimics physiological hemopoiesis.
Water Metabolism in Rats Subjected to Chronic Alcohol Administration
Authors: Parlesak Alexandr , Pohl Claus , Bode J. Christian , Bode Christiane
Published: May 2004

Aim: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion and certain renal functions in rats during a period of 12 months. Animals and Study Design: Male Wistar rats received either alcohol (15% v/v; group A, n = 65) or tap water (group C, n = 35) as drinking fluid. Urine and faeces were collected from 6 rats of each group during 7 days, at monthly intervals. In further experiments, the animals received a low-protein/high-fat diet with and without alcohol. Results: When the rats were fed the standard diet, 24-hour urine excretion was significantly reduced in group A compared with group C. This difference was even more pronounced when the animals were fed the low-protein/high-fat diet. The reduced urine excretion was not due to lower liquid consumption and the pattern of daily excretion of faeces was comparable with that observed for urine excretion. Both sodium and potassium excretion and the diuretic response to an acute water load were significantly reduced in group A compared with group C. The changes in water balance induced by chronic alcohol consumption were reversible within a few days when the rats received water instead of 15% alcohol. Conclusions: Chronic alcohol consumption has an antidiuretic effect in rats. The percentage of total ingested fluid leaving the body as hidden water loss increases after alcohol consumption by up to 25–26% over control values.
Modulatory Effect of the 23-kD Calcium Oxalate Monohydrate Binding Protein on Calcium Oxalate Stone Formation during Oxalate Stress
Authors: Asokan D. , Kalaiselvi P. , Varalakshmi P.
Published: May 2004

Aims: To isolate, characterize, and quantify the 23-kD calcium oxalate monohydrate (COM) binding protein in the urine of controls and calcium oxalate stone formers and to study its role in kidney stone formation. Methods: Calcium oxalate crystals were prepared and allowed to interact with human control kidney homogenate as well as urine of controls and calcium oxalate stone formers. EDTA extract was used for the separation of the 23-kD COM-binding protein (partially purified). This partially purified 23-kD COM-binding protein was further separated by DEAE-cellulose column chromatography. SDS-PAGE confirmed the molecular weight. An antibody was raised against the renal 23-kD COM-binding protein in rabbits. The 23-kD COM-binding protein was quantified in the urine from controls and stone formers by ELISA. Thiol group quantification, oxalate-binding assay, and calcium oxalate crystal nucleation and aggregation were performed. Morphological changes of the calcium oxalate crystals induced by the urinary 23-kDa protein were determined using scanning electron microscopy. The expression of this protein using different concentrations of oxalate was also determined in an in vitro model. Results: The urinary excretion of the 23-kD COM-binding protein varies between 0.5 and 1.5 mg/24 h in controls, while in stone former its excretion was found to range from 5 to 7 mg/24 h. The protein isolated from urine was found to inhibit crystal nucleation and aggregation in controls, while the protein isolated from stone formers exhibited less inhibitory activity with reduced thiol groups. The 23-kD COM-binding protein derived from control urine formed COM crystals and intertwined calcium oxalate dihydrate crystals in a crystal growth system, while protein isolated from stone formers’ urine induced aggregation of COM crystals. This protein expression was found to be increased with increasing concentration of oxalate in renal epithelial cells of the African green monkey kidney (VERO) cell line. Conclusions: Increased expression and excretion of the 23-kD protein was observed in oxalate stress conditions, and in stone formers this protein exhibited a promoting activity. The increased excretion of this protein with promoting activity favors the lithogenic process in stone formers.
Adjuvant Intravesical Mitoxantrone versus Recombinant Interferon-α after Transurethral Resection of Superficial Bladder Cancer: A Randomized Prospective Study
Authors: Papatsoris A.G. , Deliveliotis C. , Giannopoulos A. , Dimopoulos C.
Published: May 2004

Objective: To determine the efficacy and safety of two different doses of intravesical mitoxantrone and of recombinant interferon-α (IFNα-2b), instilled after transurethral resection (TUR) of superficial transitional cell carcinoma (TCC) of the bladder. Material and Methods: 208 patients (mean age 62.05 years) with primary or recurrent superficial (TaG1, T1G1, T1G2) bladder cancer were randomly allocated into four groups, after TUR of all visible tumors. Group A (45 patients) received no further therapy; group B (56 patients) received 10 mg of mitoxantrone (6 weekly and 20 fortnightly instillations), group C (54 patients) 20 mg of mitoxantrone (3 fortnightly and 10 monthly instillations) and group D (53 patients) received 100 MU of IFNα-2b (8 weekly, 8 fortnightly and 6 monthly instillations). Results: During the follow-up (mean 21.09 months), 29 (64.44%) patients in group A had recurrence, compared with 19 (33.92%) in group B, 17 (31.48%) in group C and 15 (28.3%) patients in group D (p < 0.005). Furthermore, the differences in simple recurrence rates were statistically more significant (p < 0.05), when group A was compared with the three other groups in the terms of T1G2, recurrent and multiple neoplasms. Twenty-nine patients (10, 7, 8, and 4 in groups A–D) experienced tumor progression, and the differences between the four groups were not statistically significant (p > 0.05). The mean recurrence time was 9.03 months in group A, 13.74 in group B, 14.24 in group C and 17.4 months in group D (p < 0.001), and the recurrence rate per 100 patient-months was 4.39, 1.57, 1.48 and 1.06, respectively (p < 0.05). Toxicity (grade 1–3) was recorded in 23.21% in group B, in 31.48% in group C and in 9.43% in group D (p < 0.01). Conclusion: The two doses of mitoxantrone resulted in similar efficacy for the prevention of superficial bladder cancer recurrences, with the dose of 10 mg of mitoxantrone being related to fewer side effects. In comparison with mitoxantrone, the adjuvant intravesical immunotherapy with 100 MU of IFNα-2b showed a better combination of efficacy and safety.
Importance of Serum p53 Antibodies during Follow-Up after Treatment of Invasive Bladder Tumors
Authors: Gumus Eyup , Demirel Gulderen , Tanriverdi Orhan , Horasanli Kaya , Özmen Gökhan , Miroglu Cengiz
Published: May 2004

Introduction: To investigate the prognostic importance of the changes in serum p53 antibody titrations during follow-up of patients who had anti-p53 antibody-positive invasive bladder tumors with transitional epithelial cells. Materials and Methods: The study group consisted of 23 clinically T3≤, N0, M0 patients with positive serum anti-p53 antibodies before treatment. 23 cases with negative serum anti-p53 antibodies who were comparable in age, comorbidity and stage with the study group were selected as a control group. The cases whose serum anti-p53 titrations decreased to normal levels after treatment were compared for metastases, death rates and survival with cases who remained serum anti-p53-positive and those who were serum p53 antibody-negative before treatment. Serum anti-p53 antibody titration was determined by ELISA. Results: While serum anti-p53 antibody titrations became negative in 8 (35%) of the 23 seropositive patients, it did not change in 15 patients (65%). There was a correlation between the maintenance of seropositivity, local progression/metastasis and death (p < 0.05). Survival was found to be better in cases who were seronegative after treatment compared with cases who remained positive and also those who were seronegative before treatment (p < 0.05). Conclusion: The normalization of serum anti-p53 antibody positivity after treatment of invasive bladder tumors seems to be a good and reliable prognostic indicator.
Clinical Manifestations and Treatment of Caries from 1953 to Global Changes in the 20th Century
Authors: König K.G.
Published: May 2004

Manifestations and treatment of caries are strongly dependent on caries risk and the severity of the attacking factors which determine the degree of caries activity. Caries activity in turn will be modified and can be minimized by effective preventive measures. Exemplary cases and events will be discussed to illustrate what has happened since the establishment of ORCA 50 years ago.
Diagnosis versus Detection of Caries
Authors: Nyvad B.
Published: May 2004

Caries diagnosis is the art or act of identifying a disease from its signs and symptoms. This is distinct from the detection of the signs and symptoms themselves. The diagnosis forms the basis for making informed treatment decisions. Hence, if there is no diagnostic step expressed in terms of the probability of present and future occurrence of disease, practitioners may resort to treatments guided by previous experiences with similar clinical manifestations. This paper reviews various methodological aspects of caries diagnostic testing. It is concluded that rather than continuing to search for the truth of the diagnosis, it may be more informative to consider the consequences of the diagnosis. This view is supported by results from caries-preventive trials in which the activity of carious lesions has been monitored longitudinally over years.