bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental correlates of mammal species richness in South America: effects of spatial structure, taxonomy and geographic range
Authors: Ruggiero Adriana , Kitzberger Thomas
Published: May 2004

Although some consensus exists regarding the positive synergism between energy and heterogeneity in increasing species diversity, the role of environmental variability remains controversial. We examine how these factors interact to explain spatial variation in mammal species richness in South America. After taking into account the effects of spatial autocorrelation and area, elevation variability and energy mainly drive spatial variation in mammal species richness. The effect of environmental variability is less important. When different taxonomic groups of mammals are analyzed separately, three ways emerge whereby energy and heterogeneity interact to promote species richness. Heterogeneity may have no effect on species richness, habitat heterogeneity and energy availability contribute independently to species richness, or heterogeneity increases in importance with an increase in energy availability. The partition of species into range size quartiles shows that habitat heterogeneity and temporal instability in the resource supply account for the species richness pattern in the narrowest‐ ranging species. Habitat heterogeneity is significant also for intermediate ranging species but not for the widest‐ranging species. Energy alone drives the species richness pattern in the latter species. The interplay between ecology and biogeographic history may ultimately explain these differences given that narrow‐ and wide‐ranging species show distinct biogeographic patterns, and different taxonomic groups also unequally represent them.
Differential expression of p53, p63 and p73 protein and mRNA for DMBA‐induced hamster buccal‐pouch squamous‐cell carcinomas
Authors: Chen Yuk‐Kwan , Huse Shue‐Sang , Lin Li‐Min
Published: May 2004

Abnormalities in the p53 gene are regarded as the most consistent of the genetic abnormalities associated with oral squamous‐cell carcinoma. Two related members of the p53 gene family, p73 and p63, have shown remarkable structural similarity to p53, suggesting possible functional and biological interactions. The purpose of this study was to investigate the differential expression of p73, p63 and p53 genes for DMBA‐induced hamster buccal‐pouch squamous‐cell carcinoma. Immunohistochemical analysis for protein expression and reverse transcriptase‐polymerase chain reaction (RT‐PCR) for mRNA expression were performed for 40 samples of hamster buccal pouches, the total being separated into one experimental group (15‐week DMBA‐treated; 20 animals) and two control groups (untreated and mineral oil‐treated; 10 animals each). Using immunohistochemical techniques, nuclear staining of p53 and p73 proteins was detected in a subset of hamster buccal‐pouch tissue specimens treated with DMBA for a period of 15 weeks, whereas p63 proteins were noted for all of the 20 hamster buccal‐pouch tissue specimens treated with DMBA for 15 weeks as well as for all of the untreated and mineral oil‐treated hamster buccal‐pouch tissue specimens. Differential expression of p63, p73 and p53 protein for the experimental group was as follows: p63+/p73+/p53+ (n = 14; 70%); p63+/p73+/p53– (n = 2; 10%); p63+/p73–/p53– (n = 4; 20%) and p63+/p73–/p53– (untreated [n = 10] and mineral oil‐treated mucosa [n = 10]; 100% each). Upon RT‐PCR, ΔNp63mRNA was detected within all of the 20 hamster buccal‐pouch tissue specimens treated with DMBA for 15 weeks, whereas expression of TAp63 was not detected. Furthermore, p73 mRNA was identified for 16 of the hamster buccal‐pouch tissue specimens treated with DMBA for 15 weeks, whereas p53 mRNA was noted for 14 15‐week DMBA‐treated pouches. The proportional (percentage) expression of ΔNp63, p73 and p53 mRNA for the hamster buccal‐pouch tissue specimens treated with DMBA for 15 weeks was noted to be consistent with the findings using immunohistochemical techniques. A significant correlation between p53, p63 and p73 expression (protein and mRNA) was demonstrated for the hamster buccal‐pouch carcinoma samples. Our results indicate that both p73 and p63 may be involved in the development of chemically induced hamster buccal‐pouch carcinomas, perhaps in concert with p53.
Deoxyribonucleic acid‐based diagnostic techniques to detect Helicobacter pylori
Authors: Ruzsovics A. , Molnar B. , Tulassay Z.
Published: May 2004

Helicobacter pylori is an important cause of many gastrointestinal disorders, ranging from chronic gastritis to gastric lymphoma and adenocarcinoma.

The deoxyribonucleic acid‐based assays have the potential to be a powerful diagnostic tool given its ability to specifically identify H. pylori deoxyribonucleic acid. Markers used to include general H. pylori structures and pathogenetic factors like ureaseA, cagA, vacA, iceA.

Deoxyribonucleic acid or bacterial ribonucleic acid for polymerase chain reaction assays can be collected from gastric biopsy, gastric juice, stool, buccal specimens. Polymerase chain reaction can yield quantitative and genotyping results with sensitivity and specificity that approaches 100%. A clear trend in the direction of the determination of quantitative H. pylori infection by real‐time polymerase chain reaction can be observed. Fluorescent in situ hybridization is suggested for routine antibiotic resistance determination. To identify the organism, deoxyribonucleic acid structure and its virulence factors may be feasible by using oligonucleotide microarray specifically recognizing and discriminating bacterial deoxyribonucleic acid and various virulence factors.

Deoxyribonucleic acid‐based H. pylori diagnosis yields higher sensitivity, however, specificity requires sophisticated labour environment and associated with higher costs.
Cholesterol lowering effect of dietary weight loss and orlistat treatment – efficacy and limitations
Authors: Erdmann J. , Lippl F. , Klose G. , Schusdziarra V.
Published: May 2004

Background : Orlistat reduces energy uptake by the impairment of fat digestion and some evidence indicates it also lowers plasma cholesterol.

Aim : To examine total, low‐density lipoprotein‐ and high‐density lipoprotein cholesterol during a weight reducing regimen, and assess the effect of orlistat in lowering cholesterol levels independent of its weight reducing efficacy.

Methods : A total of 448 patients with elevated cholesterol according to cardiovascular risk factors entered a 2 week single‐blind run‐in period on a hypocaloric diet. Of 384 patients were subsequently assigned double‐blind treatment with orlistat (3 × 120 mg/day) or placebo for 6 months in conjunction with the hypocaloric diet.

Results : Weight loss in the orlistat group was 7.4 kg vs. 4.9 kg with placebo. Total and low‐density lipoprotein cholesterol decreased by 25–30 mg/dL vs. 10–15 mg/dL with placebo. Reduction of cholesterol with orlistat was significantly greater than anticipated from weight loss alone. In patients with cardiovascular risk factors entering the study with lower cholesterol values orlistat was also superior to placebo. On the contrary, reduction of cholesterol concentrations never exceeded 20%.

Conclusion : Orlistat has a cholesterol lowering efficacy independent of its weight reducing effect. Because of the limited therapeutic effectiveness, patients at high cardiovascular risk should receive rather early additional cholesterol lowering medication during weight loss programmes.
Abuse‐related post‐traumatic stress during the childbearing year
Authors: Seng Julia S. , Low Lisa Kane , Sparbel Kathleen J. H. , Killion Cheryl
Published: May 2004

Background.  Women with abuse‐related post‐traumatic stress who are pregnant experience symptoms that nurses and midwives may not recognize or know how to respond to.

Aim.  The purpose of this article is to increase familiarity with the post‐traumatic stress disorder diagnostic framework by illustrating the symptom categories and associated features with women's descriptions of the symptoms from qualitative interviews.

Methods.  A secondary analysis was performed with data from a qualitative interview study of the maternity care experiences of 15 American women who had abuse‐related post‐traumatic stress during pregnancy. Content analysis was used to extract all participant statements describing how post‐traumatic stress disorder symptoms and associated features manifested in pregnancy. These were then juxtaposed with the post‐traumatic stress disorder diagnostic framework.

Results.  Participants’ interviews included a range of descriptions of the intrusive re‐experiencing, avoidance and numbing, and hyperarousal core symptoms of post‐traumatic stress disorder, as well as associated psychological features such as somatization, dissociation and interpersonal sensitivity, and associated behavioural features such as substance abuse, disordered eating, high‐risk sexual behaviours, suicidality, and revictimization.

Conclusions.  Limitations of this study include that it is a secondary analysis, using a small North American sample, and focusing only on abuse‐related post‐traumatic stress disorder. Descriptive information from this qualitative study may bridge the gaps between psychiatric technical language, women's subjective experiences, and clinicians’ perceptions of a woman's post‐traumatic stress reactions.
Role of extracellular signal regulated kinase 5 in neuronal survival
Authors: Cavanaugh Jane E.
Published: May 2004

The newest member of the mitogen activated protein (MAP) kinase family of proteins, extracellular signal regulated kinase 5 (ERK5; also known as big‐mitogen activated kinase 1 or BMK1) is widely expressed in many tissues including the brain. Although growth factor activation of ERK5 in non‐neuronal cells has been shown to contribute to cell proliferation, differentiation and transformation, until recently no information was available on the role of ERK5 in neuronal survival. Recent data suggests that ERK5 is activated by neurotrophic factors in primary neuronal cells and plays an important role in neurotrophin mediated neuronal survival. These data also suggest that the mechanism of ERK5‐mediated survival involves transcriptional regulation.
Role of extracellular signal regulated kinases 1 and 2 in neuronal survival
Authors: Hetman Michal , Gozdz Agata
Published: May 2004

Extracellular signal regulated kinases 1 and 2 (ERK1/2) regulate cellular responses to a variety of extracellular stimuli. In the nervous system, ERK1/2 is critical for neuronal differentiation, plasticity and may also modulate neuronal survival. In this minireview, we present evidence that supports prosurvival activity of ERK1/2 in neurons. Several reports suggest that ERK1/2 mediates neuroprotective activity of extracellular factors, including neurotrophins. In addition, ERK1/2 is activated by neuronal injury. In damaged cells, ERK1/2 activation may act as a defensive mechanism that helps to compensate for the deleterious effects of a damaging insult. The emerging mechanisms of ERK1/2‐mediated neuroprotection may involve transcriptional regulation and/or direct inhibition of cell death machinery.
ATPase activity of magnesium chelatase subunit I is required to maintain subunit D in vivo
Authors: Lake Vanessa , Olsson Ulf , Willows Robert D. , Hansson Mats
Published: May 2004

During biosynthesis of chlorophyll, Mg2+ is inserted into protoporphyrin IX by magnesium chelatase. This enzyme consists of three different subunits of ≈ 40, 70 and 140 kDa. Seven barley mutants deficient in the 40 kDa magnesium chelatase subunit were analysed and it was found that this subunit is essential for the maintenance of the 70 kDa subunit, but not the 140 kDa subunit. The 40 kDa subunit has been shown to belong to the family of proteins called ‘ATPases associated with various cellular activities’, known to form ring‐shaped oligomeric complexes working as molecular chaperones. Three of the seven barley mutants are semidominant mis‐sense mutations leading to changes of conserved amino acid residues in the 40 kDa protein. Using the Rhodobacter capsulatus 40 and 70 kDa magnesium chelatase subunits we have analysed the effect of these mutations. Although having no ATPase activity, the deficient 40 kDa subunit could still associate with the 70 kDa protein. The binding was dependent on Mg2+ and ATP or ADP. Our study demonstrates that the 40 kDa subunit functions as a chaperon that is essential for the survival of the 70 kDa subunit in vivo. We conclude that the ATPase activity of the 40 kDa subunit is essential for this function and that binding between the two subunits is not sufficient to maintain the 70 kDa subunit in the cell. The ATPase deficient 40 kDa proteins fail to participate in chelation in a step after the association of the 40 and 70 kDa subunits. This step presumably involves a conformational change of the complex in response to ATP hydrolysis.
Characterization of mammalian eIF4E‐family members
Authors: Joshi Bhavesh , Cameron Amy , Jagus Rosemary
Published: May 2004

The translational factor eukaryotic initiation factor 4E (eIF4E) is a central component in the initiation and regulation of translation in eukaryotic cells. Through its interaction with the 5′ cap structure of mRNA, eIF4E functions to recruit mRNAs to the ribosome. The accumulation of expressed sequence tag sequences has allowed the identification of three different eIF4E‐family members in mammals termed eIF4E‐1, eIF4E‐2 (4EHP, 4E‐LP) and eIF4E‐3, which differ in their structural signatures, functional characteristics and expression patterns. Unlike eIF4E‐1, which is found in all eukaryotes, orthologues for eIF4E‐2 appear to be restricted to metazoans, while those for eIF4E‐3 have been found only in chordates. Like prototypical eIF4E‐1, eIF4E‐2 was found to be ubiquitously expressed, with the highest levels in the testis. Expression of eIF4E‐3 was detected only in heart, skeletal muscle, lung and spleen. Similarly to eIF4E‐1, both eIF4E‐2 and eIF4E‐3 can bind to the mRNA cap‐structure. However, in contrast to eIF4E‐1 which interacts with both the scaffold protein, eIF4G and the translational repressor proteins, the eIF4E‐binding proteins (4E‐BPs), eIF4E‐2 and eIF4E‐3 each possesses a range of partial activities. eIF4E‐2 does not interact with eIF4G, but does interact with 4E‐BPs. Conversely, eIF4E‐3 interacts with eIF4G, but not with 4E‐BPs. Neither eIF4E‐2 nor eIF4E‐3 is able to rescue the lethality ofeIF4Egene deletion in yeast. It is hypothesized that each eIF4E‐family member fills a specialized niche in the recruitment of mRNAs by the ribosome through differences in their abilities to bind cap and/or to interact with eIF4G and the 4E‐BPs.
Usefulness of microchip electrophoresis for reliable analyses of nonstandard DNA samples and subsequent on‐chip enzymatic digestion
Authors: Kataoka Masatoshi , Inoue Sonoko , Kajimoto Kazuaki , Sinohara Yasuo , Baba Yoshinobu
Published: May 2004

The Hitachi SV1100 utilizes capillary electrophoresis on a microchip that is capable of rapidly sizing DNA fragments. Reproducibility of electrophoresis in different channels was shown by comparing the migration times of the internal controls, DNA fragments of 100 and 800 bp. The range of DNA sizing for this microchip is between 100 and 800 bp, and accuracy in sizing of a 322 bp DNA fragment of a pUC118 PvuII digest was observed, independent of DNA concentration. Although relatively good quantification of this fragment was observed with a DNA concentration of 1.83 ng·µL−1, error increased in a dose‐dependent manner. Furthermore, the feasibility of sequential analysis with this microchip was shown by the reproducibility of successive electrophoreses of the internal control in one channel. When the pUC118 PvuII digest was treated with endonuclease KpnI on the microchip for 10 min, sequential analysis showed that the 322 bp fragment completely disappeared and two peaks corresponding to the 130 and 192 bp fragments appeared. This analysis was performed within 4 min, and the peaks were estimated as 127 and 183 bp, respectively. These results indicate the potential of on‐microchip endonuclease treatment of plasmid DNA with sequential analysis, offering high resolution in a short time.
High rate of complications associated with peripherally inserted central venous catheters in patients with solid tumours
Authors: Cheong K. , Perry D. , Karapetis C. , Koczwara B.
Published: May 2004

Abstract

Background : Peripherally inserted central catheters (PICC) have been used extensively as a cost‐effective and safe form of medium‐term intravascular access. There are only limited data about complications of PICC lines in oncology patients despite theoretical concerns about the higher risks of complications in these patients as a result of cancer itself and cancer therapy.

Aims : To document the frequency and type of PICC complications in patients with solid tumours.

Methods : All patients with solid tumours who were treated at Flinders Medical Centre, Adelaide, South Australia, Australia between January 2000 and March 2001 were included in a retrospective review of PICC complications.

Results : Twenty‐seven PICC lines were inserted in 17 patients; 40.7% (11/27) of PICC lines developed complications requiring early removal of the PICC. Complications encountered were sepsis (systemic and cellulitis), thrombosis, blockage and leakage. Septic complications were found at a rate of 8/1000 PICC days or 25.7% (7/27) of PICC inserted. The median dwell time was 20 days. The mean time for a complication to occur was 27.5 days.

Conclusions : The present study demonstrates a high rate of complications, which is higher than the complication rates reported in studies of non‐oncology patients. PICC lines should be used with caution in patients with solid tumours. Prospective studies of the factors influencing the incidence of complications might be warranted. (Intern Med J 2004; 34: 234−238)
Evaluation of a local optometric diabetic retinopathy screening service
Authors: Warburton T. J. , Hale P. J. , Dewhurst J. A.
Published: May 2004

Aims  To determine the sensitivity and specificity for sight‐threatening eye disease (STED) of the diabetic retinopathy screening scheme for Stockport during the period 1 April 2000 to 31 March 2001.

Methods  A random sample of screen‐negative patients was recalled for further assessment by consultant ophthalmologists. Screen‐positive patients, who were referred, were tracked through the hospital system to determine the outcome.

Results  In a 12‐month period, 3510 individuals with diabetes were screened, which is 1.2% of the district population. Sensitivity for STED was 75.8%[95% confidence interval (CI) 49.3, 99.99] and specificity for STED was 99.0% (95% CI 98.6, 99.3).

Conclusions  The current screening arrangements in Stockport are satisfactory in terms of sensitivity and specificity. Population coverage was 1.2% over 12 months and 1.5% over 15 months and needs to be improved. An integrated computerized register requires further development.
ROMEO: rethink organization to improve education and outcomes
Authors: Porta M. , Trento M. ,   on behalf of the ROMEO Writing Committee
Published: May 2004

Aims  Scarcity of resources, expertise and evidence‐based models have so far limited delivery of patient‐centred diabetes education. We have developed and validated a group care approach that is applicable to everyday clinical practice and cost‐effective in improving metabolic control, knowledge of diabetes, health behaviours, and quality of life in Type 2 diabetes. A clinical trial (ROMEO) was planned to evaluate applicability and reproducibility of group care in other outpatients facilities and assess its impact on a larger patient population.

Methods  Multicentre, randomized, controlled clinical trial of group vs. individual care in the routine management of Type 2 diabetes. Nine hundred patient aged < 80, with diabetes of ≥1 year known duration, treated by either diet alone or diet and oral agents, will be recruited in 15 centres and followed for 4 years. Training of physicians, nurses and dieticians included preparation of operating manual and videos, interactive sessions, and evaluation of local facilities and resources.

Results  Primary measurements: 3‐monthly HbA1c, fasting blood glucose, body weight, waist–hip ratio, yearly blood lipids, and bi‐yearly assessment of knowledge of diabetes, health behaviours and quality of life. Secondary outcomes: systolic and diastolic blood pressure, evaluation of ECG for ischaemia and QT interval, hypoglycaemic and anti‐hypertensive medication and cardiovascular events. Analysis will be by intention‐to‐treat.

Discussion If ROMEO confirms that group care can be successfully implemented in different clinics, a novel clinico‐pedagogic tool will have been acquired to support patient‐centred education, improve lifestyle and outcomes, support team work, enhance providers’ attitudes and competencies and ameliorate diabetes care organization.
Acute brain injury in hypoglycaemia‐induced hemiplegia
Authors: Shirayama H. , Ohshiro Y. , Kinjo Y. , Taira S. , Teruya I. , Nakachi K. , Tawata M. , Takasu N.
Published: May 2004

Background  The development of hemiplegia as a result of hypoglycaemia was first described in 1928. However, the mechanism remains unclear.

Case report  We report a case of a 58‐year‐old male with diabetes, who developed left hemiplegia during a severe hypoglycaemic event.

Results  Diffusion‐weighted magnetic resonance imaging detected an increased signal intensity in the pons, indicating that the patient's hemiplegia resulted from acute brain injury.

Conclusions  This report provides evidence that acute brain injury may be a cause of the neurological deficit.
Plasma and urinary vascular endothelial growth factor and diabetic nephropathy in Type 2 diabetes mellitus
Authors: Kim N. H. , Kim K. B. , Kim D. L. , Kim S. G. , Choi K. M. , Baik S. H. , Choi D. S. , Kang Y. S. , Han S. Y. , Han K. H. , Ji Y. H. , Cha D. R.
Published: May 2004

Aims  Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetes mellitus. We determined whether alterations of plasma and urinary VEGF levels are related to diabetic nephropathy in Type 2 diabetic patients.

Methods  One hundred and seven patients and 47 healthy controls were studied. Study subjects were divided into four groups using urinary albumin‐to‐creatinine ratio (ACR): a non‐diabetic healthy control group (n = 47), a normoalbuminuric diabetic group (n = 37), a microalbuminuric diabetic group (n = 37) and an overt proteinuric diabetic group (n = 33). VEGF levels were measured by enzyme‐linked immunosorbent assay.

Results  (i) Urinary VEGF concentrations were significantly higher in the diabetic groups, even at the normoalbuminuric stage (log VEGF/Cr, normoalbuminuria; 4.33 ± 1.06 vs. control; 3.53 ± 0.79, P = 0.009). Urinary VEGF excretions increased as diabetic nephropathy advanced. (ii) Plasma and urinary VEGF levels were higher in hypertensive diabetic patients than in the normotensive individuals with diabetes. (iii) In those with diabetes, plasma VEGF levels were found to be positively correlated with plasma urea (r = 0.398, P = 0.039) and urinary ACR (r = 0.251, P = 0.044), and urinary VEGF to be positively correlated with urinary ACR (r = 0.645, P < 0.001), and creatinine (r = 0.336, P = 0.009), and to be negatively correlated with serum albumin (r = −0.557, P < 0.001). Urinary VEGF and serum creatinine were independently correlated with urinary ACR.

Conclusions  Urinary excretion of VEGF increased during the earlier stage of diabetic nephropathy and was significantly correlated with urinary albumin excretion. This suggests that urinary VEGF might be used as a sensitive marker of diabetic nephropathy and for predicting disease progression.
Development and progression of diabetic retinopathy in patients with Type 1 diabetes who are positive for GAD autoantibody
Authors: Mimura T. , Funatsu H. , Uchigata Y. , Kitano S. , Shimizu E. , Noma H. , Amano S. , Araie M. , Iwamoto Y. , Hori S.
Published: May 2004

Aims  To investigate the relationship between autoantibodies to glutamic acid decarboxylase (GAD) and proliferative diabetic retinopathy (PDR) to assess the role of autoimmunity in retinopathy.

Methods  Patients with Type 1 diabetes for more than 10 years who had been diagnosed under age 30 (13–28 years) were studied. They were classified into three groups. The PDR group consisted of 22 patients, the pre‐PDR group was 26 patients, while the non‐DR group was 32 patients who had Type 1 diabetes without retinopathy. Blood was collected to measure autoantibodies to GAD, and the relationship between PDR and GAD positivity was investigated in a cross‐sectional study.

Results  The highest positivity rate of GAD autoantibodies was 50.0% in the non‐DR group, followed by the pre‐PDR group (30.8%) and the PDR group (18.2%).

Conclusions  Production or existence of GAD autoantibodies may contribute to the prevention of retinopathy.
Why Does Employment Legislation Not Damage Small Firms?
Authors: Edwards Paul , Ram Monder , Black John
Published: May 2004

Business rhetoric and conventional theory expect that employment regulations will have negative effects on small firms. Prior research has shown that effects are quite rare, but has not explained why. Case studies of 18 firms from three sectors identified four explanations. (1) Perceptions of effects tend to be broad and general, rather than reflections of concrete experience. (2) ‘The law’ is not uniform, with older laws being largely taken for granted. (3) Effects depend on competitive conditions, which are more important influences on firms than are regulations; where conditions are benign, regulations can be absorbed, but in other circumstances employment regulations can exacerbate competitive pressures. (4) A degree of informality in small firms further eases responses. By the same token, however, hopes that regulation will stimulate modernization are rarely realized.
On Optimality of Bayesian Wavelet Estimators
Authors: Abramovich Felix , Amato Umberto , Angelini Claudia
Published: May 2004

Abstract.  We investigate the asymptotic optimality of several Bayesian wavelet estimators, namely, posterior mean, posterior median and Bayes Factor, where the prior imposed on wavelet coefficients is a mixture of a mass function at zero and a Gaussian density. We show that in terms of the mean squared error, for the properly chosen hyperparameters of the prior, all the three resulting Bayesian wavelet estimators achieve optimal minimax rates within any prescribed Besov space for p ≥ 2. For 1 ≤ p < 2, the Bayes Factor is still optimal for (2s+2)/(2s+1) ≤ p < 2 and always outperforms the posterior mean and the posterior median that can achieve only the best possible rates for linear estimators in this case.
The regulation of rhinovirus infection in vitro by IL‐8, HuIFN‐α, and TNF‐α
Authors: BERG KURT , ANDERSEN HENNING , OWEN TERENCE C.
Published: May 2004

The influence of three important cytokines (IL‐8, TNF‐α, and HuIFN‐α) on ongoing rhinovirus infections has been examined in vitro, individually or as combinations. TNF‐α was able to transform traces of HRV infections into full‐blown infections. Furthermore, TNF‐α was able to down‐regulate the antiviral action of HuIFN‐α completely, even at levels of just a few pg/ml. This suggests that the induction of TNF‐α by HRV may be part of the virus's strategy to minimize the interferon response which is part of the host's immune defence system. However, troxerutin (a flavonoid) was able to neutralize the downregulatory action of TNF‐α on the HuIFN‐α system at low levels and re‐establish the antiviral activity ascribed to IFN‐α. IL‐8 exerted a minor influence on the interferon system, and had no influence on rhinovirus infections. The in vitro findings are supported, in part, by recent in vivo findings in a common cold pilot study.
Multilocular cystic renal cell carcinoma: a clinicopathological, immuno‐ and lectin histochemical study of nine cases
Authors: IMURA JOHJI , ICHIKAWA KAZUHITO , TAKEDA JUN , TOMITA SHIGEKI , YAMAMOTO HIDENOBU , NAKAZONO MASAAKI , TAKIMOTO TOSHIRO , UEDA YOSHIHIKO , FUJIMORI TAKAHIRO
Published: May 2004

Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon variant of renal neoplasm and its histogenesis is unclear. The aim of this study was to use immuno‐ and lectin histochemistry to delineate histochemical patterns which might indicate the histogenetic origin of MCRCC from a particular part or parts of the nephron. We present our experience with nine cases of MCRCC. Fifteen cases of renal cell carcinoma with cystic degeneration (RCC‐CD) were selected for comparison with MCRCC. We carried out clinicopathological and immunohistochemical examinations of the MCRCC cases. Clinically, the prognosis of the patients was quite good, in that all nine patients are alive and without recurrence at the time of this report. The MCRCCs reacted strongly in a higher proportion of cases with the distal nephron markers, such as peanut agglutinin (PNA, 88.9%) and MUC1–core antibody (MUC1, 100%), but none reacted preferentially with proximal nephron markers such as vimentin, Leu M1 and Lotus tetragonolobus (LTA). The RCC‐CD tumours reacted with vimentin (40%), Leu M1 (66.7%) and LTA (86.7%). Except for two cases, the RCC‐CD tumours did not react with PNA or MUC1 core antibody. These results illustrate the different patterns of expression of MCRCC and RCC‐CD and suggest that MCRCC originates from the distal nephron. Therefore, MCRCC should be differentiated from other types of renal cell carcinoma on the basis of the histogenesis of the tumour and the clinicopathological findings.
Early segmental changes in ischemic acute tubular necrosis of the rat kidney
Authors: FAARUP POUL , HOLSTEIN‐RATHLOU NIELS‐HENRIK , NØRGAARD TOVE , HEGEDÜS VIKTOR
Published: May 2004

The background and mechanisms of ischemic acute tubular necrosis are still essentially unclarified. Therefore a quantitative morphological technique was applied for evaluation of the early structural changes in different fractions of the proximal convoluted tubule in the rat renal cortex. In male pentothal‐anesthetized Wistar rats (body weight 200–250 g) ischemia of the right kidney was obtained by clamping (clamp diameter 0.15 mm) the ipsilateral renal artery for varying periods of time (10 min to 6 h) followed by removal and instant freezing of the kidney in isopentane at −165 °C and subsequent freeze‐substitution in alcohol. The microscopic slides from the kidneys were silver methenamine‐PAS stained. In the segments of the proximal convoluted tubules of the nephrons, presence of nuclear pyknosis, places of denuded basement membranes and presence of exfoliated tubular cells were counted. The results were statistically treated for comparison between the extent of damage in the initial postglomerular fraction and the later tubular loops. All three parameters showed a systematic, statistically significant increased number of lesions in the initial fraction of the proximal convoluted tubule versus the subsequent loops. The distribution of the structural lesions is in accordance with the previously reported presence of a tubulo‐capillary counter‐current flow in the proximal convoluted tubule and, when related to the highly variable oxygen tension in the normal renal cortex of the rat, indicates that the peculiar location of the early lesions might well be determined by these functional conditions.
Omp35, a New
Enterobacter aerogenes
Porin Involved in Selective Susceptibility to Cephalosporins
Authors: Bornet Charléric , Saint Nathalie , Fetnaci Lilia , Dupont Myrielle , Davin-Régli Anne , Bollet Claude , Pagès Jean-Marie
Published: May 2004

In
Enterobacter aerogenes
, β-lactam resistance often involves a decrease in outer membrane permeability induced by modifications of porin synthesis. In ATCC 15038 strain, we observed a different pattern of porin production associated with a variable antibiotic susceptibility. We purified Omp35, which is expressed under conditions of low osmolality and analyzed its pore-forming properties in artificial membranes. This porin was found to be an OmpF-like protein with high conductance values. It showed a noticeably higher conductance compared to Omp36 and a specific location of WNYT residues in the L3 loop. The importance of the constriction region in the porin function suggests that this organization is involved in the level of susceptibility to negative large cephalosporins such as ceftriaxone by bacteria producing the Omp35 porin subfamily.
Salivary testosterone and cortisol in rugby players: correlation with psychological overtraining items
Authors: Maso F , Lac G , Filaire E , Michaux O , Robert A
Published: May 2004

Background:A psychocomportemental questionnaire has been devised by the consensus group of the Société Française de Médecine du Sport to characterise and quantify, using a list of functional and psychocomportemental signs, a state of “staleness”, for which no biological indicator is unanimously recognised.

Objectives:To determine the relation between this diagnostic method and two hormones (cortisol and testosterone) often used as indicators of a state of fitness or staleness.

Methods:The subjects were young rugby players. They were asked to complete the overtraining questionnaire and gave three saliva samples (at 8 am, 11 am, and 5 pm) during a rest day. Concentrations of cortisol and testosterone in the saliva were determined by radioimmunoassay.

Results:A preferential relation was found between the questionnaire score and testosterone concentration but not between the questionnaire score and cortisol concentration.

Conclusions:The questionnaire may be a useful tool for screening subjects at risk of overtraining. Testosterone concentration is influenced by tiredness, and is therefore a valid marker of tiredness.
THETA FUNCTIONS ON THE MODULI SPACE OF PARABOLIC BUNDLES
Authors: GAVIOLI FRANCESCA
Published: May 2004

In this paper we extend the result on base point freeness of the powers of the determinant bundle on the moduli space of vector bundles on a curve. We describe the parabolic analogues of parabolic theta functions, then we determine a uniform bound depending only on the rank of the parabolic bundles. In order to get this bound, we construct a parabolic analogue of Grothendieck's scheme of quotients, which parametrizes quotient bundles of a parabolic bundle, of fixed parabolic Hilbert polynomial. We prove an estimate for its dimension, which extends the result of Popa and Roth on the dimension of the Quot scheme. As an application of the theorem on base point freeness, we characterize parabolic semistability on the algebraic stack of quasi-parabolic bundles as the base locus of the linear system of the parabolic determinant bundle.
PINNING MECHANISM AND FLUX MOTION IN YBa2Cu3O7 THIN FILMS
Authors: DEMIREL ALI IHSAN
Published: May 2004

The flux creep phenomena and the J c characteristics have been investigated in the YBa 2 Cu 3 O 7 (YBCO) thin films grown by metal organics chemical vapor deposition (MOCVD) technique. The anisotropy of the current density (J c ) is discussed on the basis of the intrinsic pinning model and the anisotropic critical magnetic field (H c2 ). The properties of the high J c and the pinning energy are related with the fine precipitates observed by tunneling electron microscopy (TEM). The strong pinning mechanism affects the amount of the flux motion.
WAVE FUNCTIONS WITH DISCRETE AND WITH CONTINUOUS SPECTRUM FOR QUANTUM DAMPED HARMONIC OSCILLATOR PERTURBED BY A SINGULARITY
Authors: CHOI JEONG-RYEOL
Published: May 2004

The quantum states with discrete and continuous spectrum for the damped harmonic oscillator perturbed by a singularity have been investigated using invariant operator and unitary operator together. The eigenvalue of the invariant operator for ω0≤β/2 is continuous while for ω0>β/2 is discrete. The wave functions for ω0=β/2 expressed in terms of the Bessel function and for ω0<β/2 in terms of the Kummer confluent hypergeometric function. The convergence of the probability density is more rapid for over-damped harmonic oscillator than that of the other two cases due to the large damping constant.
STRUCTURE AND DYNAMICS OF CARBON NANOTUBES IN CONTACT WITH GRAPHITE SURFACE AND OTHER CONCENTRIC NANOTUBES
Authors: GUPTA SHUCHI , DHARAMVIR KEYA , JINDAL V. K.
Published: May 2004

Rigid carbon nanotubes in single and double walled formations, placed on a graphite surface, are bounced, rotated, slid and rolled. Various features associated with these motions are studied by assuming a 6-exp form of interaction (Van der Waal's attraction and Born–Mayer repulsion) among the C-atoms. Calculations reported here are for tubes of diameter around 14 Å, for which rigid tube approximation is known to work well. The oscillatory motion corresponding to rolling has the softest mode, whereas the one with highest frequency corresponds to bouncing. The energy barriers corresponding to these motions are also reported in this paper. The rotational and translational energy barriers for the movement of one nanotube with respect to the other one, in a double walled nanotube, have also been studied and it turns out that these tubes rotate and slide freely at room temperature. The translational energy barrier, in case of zigzag tubes, is interestingly, an order of magnitude higher than that of armchair tubes. In case of rotation, the case is reverse. Furthermore, it turns out that any drag of a concentric nanotube along the long axis direction is coupled with rotation, indicating easy screw motion instead of a simple drag. We also describe the dynamics of translational telescopic motion of a multiwalled nanotube assembly where a core oscillates within an open ended outer shell assembly.
ON A CLASS OF CYCLICALLY PRESENTED GROUPS
Authors: EDJVET MARTIN , HAMMOND PAUL
Published: May 2004

This paper considers the problem for what n and ω is the cyclically presented group Gn(ω) irreducible and trivial and studies the case when [Formula: see text] and n≥5.
EVIDENCE OF TIME-DEPENDENT TENSILE RESPONSE IN INTACT HUMAN TENDON
Authors: MAGANARIS CONSTANTINOS N.
Published: May 2004

The present study was performed to establish whether intact human tendons exhibit time-dependent tensile properties, as they do in the in vitro state. Measurements were taken in seven men and involved ultrasound-based recording of the gastrocnemius tendon elongation during three sets of five repeated isometric plantarflexion contractions elicited by tetanic electrical stimulation. The plantarflexion moment corresponding to the tendon elongation in the fifth contraction presented a pattern dependent on the voltage applied: it was approximately constant when applying 50% of maximal voltage, but it decreased curvilinearly as a function of contraction number when applying 70 and 100% of maximal voltage, reaching in the fifth contraction 84% of the plantarflexion moment corresponding to the elongation examined in the first contraction. These results suggest that, once a threshold tendon elongation is undergone, in vivo tendons may exhibit substantial viscoelasticity. The present findings have implications for muscle and joint function and need to be accounted for by musculoskeletal models.
Volume changes and whole cell membrane currents activated during gradual osmolarity decrease in C6 glioma cells: contribution of two types of K+ channels
Authors: Ordaz B. , Vaca L. , Franco R. , Pasantes-Morales H.
Published: May 2004

Volume changes and whole cell ionic currents activated by gradual osmolarity reductions (GOR) of 1.8 mosM/min were characterized in C6 glioma cells. Cells swell less in GOR than after sudden osmolarity reductions (SOR), the extent of swelling being partly Ca2+ dependent. In nominally Ca2+-free conditions, GOR activated predominantly whole cell outward currents. Cells depolarized from the initial −79 mV to a steady state of −54 mV reached at 18% osmolarity reduction [hyposmolarity of −18% (H-18%)]. Recordings of Cl− and K+ currents showed activation at H-3% of an outwardly rectifying Cl− current, with conductance of 1.6 nS, sensitive to niflumic acid and 5-nitro-2-(3-phenylpropylamino)benzoic acid, followed at H-18% by an outwardly rectifying K+ current with conductance of 4.1 nS, inhibited by clofilium but insensitive to the typical K+ channel blockers. With 200 nM Ca2+ in the patch pipette, whole cell currents activated at H-3% and at H-13% cells depolarized from −77 to −63 mV. A K+ current activated at H-1%, showing a rapid increase in conductance, suppressed by charybdotoxin and insensitive to clofilium. These results show the operation of two different K+ channels in response to GOR in the same cell type, activated by Ca2+ and osmolarity and with different osmolarity activation thresholds. Taurine and glutamate efflux, monitored by labeled tracers, showed delayed osmolarity thresholds of H-39 and H-33%, respectively. This observation clearly separates the Cl− and amino acid osmosensitive pathways. The delayed amino acid efflux may contribute to counteract swelling at more stringent osmolarity reductions.
Non-cross-bridge calcium-dependent stiffness in frog muscle fibers
Authors: Bagni M. A. , Colombini B. , Geiger P. , Berlinguer Palmini R. , Cecchi G.
Published: May 2004

At the end of the force transient elicited by a fast stretch applied to an activated frog muscle fiber, the force settles to a steady level exceeding the isometric level preceding the stretch. We showed previously that this excess of tension, referred to as “static tension,” is due to the elongation of some elastic sarcomere structure, outside the cross bridges. The stiffness of this structure, “static stiffness,” increased upon stimulation following a time course well distinct from tension and roughly similar to intracellular Ca2+ concentration. In the experiments reported here, we investigated the possible role of Ca2+ in static stiffness by comparing static stiffness measurements in the presence of Ca2+ release inhibitors (D600, Dantrolene, 2H2O) and cross-bridge formation inhibitors [2,3-butanedione monoxime (BDM), hypertonicity]. Both series of agents inhibited tension; however, only D600, Dantrolene, and 2H2O decreased at the same time static stiffness, whereas BDM and hypertonicity left static stiffness unaltered. These results indicate that Ca2+, in addition to promoting cross-bridge formation, increases the stiffness of an (unidentified) elastic structure of the sarcomere. This stiffness increase may help in maintaining the sarcomere length uniformity under conditions of instability.
Protein synthesis rates of human PBMC and PMN can be determined simultaneously in vivo by using small blood samples
Authors: Walrand Stéphane , Guillet Christelle , Gachon Pierre , Rousset Paulette , Giraudet Christophe , Vasson Marie-Paule , Boirie Yves
Published: May 2004

Immune cell functions can be evaluated in vivo by measuring their specific protein fractional synthesis rates (FSR). Using stable isotope dilution techniques, we describe a new method allowing simultaneous in vivo assessment of FSR in two leukocyte populations in healthy human subjects, using small blood samples. Peripheral blood mononuclear cell (PBMC) and polymorphonuclear neutrophil (PMN) FSR were measured during primed continuous intravenous infusion of l-[1-13C]leucine. Immune cells from 6 ml of whole blood were isolated by density gradient centrifugation. In a first study, we calculated the FSR using plasma [13C]leucine or α-[13C]ketoisocaproate (KIC) enrichments as precursor pools. In a second study, we compared protein FSR in leukocytes, using enrichments of either intracellular or plasma free [13C]leucine as immediate precursor pools. The present approach showed a steady-state enrichment of plasma and circulating immune cell free [13C]leucine precursor pools. The linearity of labeled amino acid incorporation rate within mixed PBMC and PMN proteins also was verified. Postabsorptive protein FSR was 4.09 ± 0.39%/day in PBMC and 1.44 ± 0.08%/day in PMN when plasma [13C]KIC was the precursor pool. The difference between PBMC and PMN FSR was statistically significant, whatever the precursor pool used, suggesting large differences in their synthetic activities and functions. Use of the plasma [13C]KIC pool led to an underestimation of leukocyte FSR compared with the intracellular pool (PBMC: 6.04 ± 0.94%/day; PMN: 2.98 ± 0.30%/day). Hence, the intracellular free amino acid pool must be used as precursor to obtain reliable results. In conclusion, it is possible to assess immune cell metabolism in vivo in humans by using small blood samples to directly indicate their metabolic activity in various clinical situations and in response to regulating factors.
Dose Escalation Study of Paclitaxel in Combination with Fixed-Dose Irinotecan in Patients with Advanced Non-Small Cell Lung Cancer (JCOG 9807)
Authors: Yamada Kouzo , Ikehara Mizuki , Tanaka Gaku , Nomura Ikuo , Oshita Fumihiro , Noda Kazumasa
Published: May 2004

Background: Both irinotecan (CPT) and paclitaxel (Pac) are effective against non-small cell lung cancer (NSCLC), and besides, preclinical studies have demonstrated an additive or synergistic interaction between camptothecin and taxane. Methods: We conducted a phase I/II study of combination chemotherapy consisting of Pac and CPT to determine qualitative and quantitative toxicities and efficacy of the combination against advanced NSCLC. We fixed the dose of CPT at 60 mg/m2 and escalated the Pac dose in 10 or 20 mg/m2 increments from a starting dose of 80 mg/m2, and repeated the cycle every 2 weeks. Prophylactic G-CSF was also administered. Results: Between February 1999 and April 2001, 24 patients were registered in the study. None of the patients had a history of prior chemotherapy, but surgical resection had been performed in 3 of them. None of the patients experienced dose-limiting toxicity (DLT) up to and including level 6. At dose level 7 of Pac, 180 mg/m2, 2 patients experienced DLT, that is grades 2 and 3 dyspnea due to pneumonitis. Another patient experienced grade 1 dyspnea due to pneumonitis. Neutropenia, diarrhea, and other toxicities were mild; however, we concluded that dose level 7 of Pac was the maximum-tolerated dose. An objective response was observed in 58.3%. The median survival time was 370 days, and the 1-year survival rate was 54.2%. Conclusion: Pneumonitis was the DLT in this study, and Pac 160 mg/m2 and CPT 60 mg/m2 every 2 weeks are recommended for the phase II study. This combination shows appreciable activity against NSCLC.
Paclitaxel Treatment of Breast Cancer Cell Lines Modulates Fas/Fas Ligand Expression and Induces Apoptosis Which Can Be Inhibited through the CD40 Receptor
Authors: Stumm Susanne , Meyer Anke , Lindner Matthias , Bastert Gunter , Wallwiener Diethelm , Gückel Brigitte
Published: May 2004

Objective: Cytotoxic chemotherapy of advanced breast cancer is frequently complicated by drug resistance. Our goal was to define the role of the apoptosis-regulating receptors Fas (CD95) and CD40 in the chemosensitivity of breast cancer. Methods: The sensitivity of four breast cancer cell lines to paclitaxel and mitoxantrone was evaluated using an ATP-based cell viability assay. After verification of apoptosis by annexin V staining and TUNEL assay, cell lines were characterized regarding their constitutive expression of both surface and soluble (s)Fas (CD95) and Fas ligand (Fas-L). The role of the Fas/Fas-L system and different caspases was assessed by blocking drug-mediated apoptosis with specific antibodies. Finally, the paclitaxel sensitivity of the CD40-negative cell line KS was compared to that of its CD40-positive transfectant KS-CD40. Results and Conclusion: While the cytotoxic effect of mitoxantrone did not correlate with Fas expression, the results presented here suggest some involvement of the Fas/Fas-L system in paclitaxel-induced apoptosis. Cell lines with constitutive expression of Fas/sFas demonstrated a higher sensitivity to paclitaxel than Fas-negative cells. Incubation with paclitaxel led to a measurable downregulation of the expression of both soluble and surface Fas receptor in these cells. Interestingly, stimulation of the CD40 receptor inhibited paclitaxel-induced apoptosis in the transfected cell line KS-CD40, suggesting a role of this receptor in the modulation of chemosensitivity.