bluuebunny/crossref_metadata_2025 huggingface dataset:
The human hedgehog-interacting protein gene: Structure and chromosome mapping to 4q31.21→q31.3
Authors: Bak M. , Hansen C. , Friis Henriksen K. , Tommerup N.
Published: April 2003

Hedgehog-interacting protein (Hhip) is a novel regulatory component in the vertebrate hedgehog-signalling pathway. The murine Hhip encodes a type I TM protein that attenuates hedgehog signalling by binding all three mammalian hedgehog proteins. Here we describe the cloning and characterisation of the homologous human hedgehog-interacting protein gene (HHIP). HHIP comprises 13 exons and spans >91kb encoding a protein of 700 aa which shares 94% sequence iden- tity with mouse Hhip. HHIP maps to chromosome 4q31.21→ q31.3. Additionally, we have mapped murine Hhip to chromosome 8.
Genomic structure, chromosomal localization, and embryonic expression of the mouse homolog of PRCC, a gene associated with papillary renal cell carcinoma
Authors: Weterman M.A.J. , Wilbrink M. , Eleveld M. , Merkx G. , van Groningen J.J.M. , van Rooijen M. , Geurts van Kessel A.
Published: April 2003

In a subset of papillary renal cell carcinomas a t(X;1)(p11;q21) chromosome translocation has repeatedly been reported. Positional cloning has demonstrated that, as a result of this translocation, the transcription factor TFE3 gene on the X-chromosome becomes fused to a novel gene, PRCC, on chromosome 1. Since as yet little is known about the function of PRCC, we sought to identify the mouse counterpart of the PRCC gene. Isolation and sequence analysis of a mouse Prcc cDNA revealed a high level of conservation between man and mouse, both at the nucleotide and protein level. As the human PRCC gene, the mouse Prcc gene is ubiquitously expressed. It shows low expression in all mouse fetal tissues examined. In addition, we identified a genomic cosmid clone containing the complete Prcc gene. The mouse Prcc gene consists of seven exons, all of which contain coding sequences. The small second exon, which was found to be located adjacent to the t(X;1) breakpoint in the human gene on chromosome 1, is also conserved between man and mouse. In mouse, Prcc is located on chromosome 3. These cDNA and genomic clones will be instrumental in the creation of mouse models for a further elucidation of the function of PRCC.
Facilitating haplotype analysis by fully automated analysis of all chromosomes in human-mouse hybrid cell lines
Authors: Langer S. , Jentsch I. , Gangnus R. , Yan H. , Lengauer C. , Speicher M.R.
Published: April 2003

Recent evidence suggests that haplotype analysis is essential in recognizing genetic factors involved in the tendency toward a particular disease or pharmacogenetic phenotype, as well as to identify genes involved in multigenic disorders. Because of the increasing need for efficient haplotype tests, a new hybrid system, called conversion technology, was developed. Conversion technology aims at converting the diploid chromosome content into a haploid state so that hybrids contain a single copy of any desired chromosome. A number of mutations can now be identified easily, as they are no longer obscured by the normal sequence present on the other copy of the chromosome. However, the efficient use of this hybrid system depends on a complete analysis of both human and mouse chromosome complements in order to assess the stability of the hybrid cells and to accurately determine their human chromosome content. We describe a new multicolor FISH-based method capable of analyzing both genomes simultaneously in a single hybridization. This new technique should become an instrumental part of inexpensive, reliable haplotype tests.
Molecular cloning of a human novel type I cytokine receptor related to δ1/TSLPR
Authors: Tonozuka Y. , Fujio K. , Sugiyama T. , Nosaka T. , Hirai M. , Kitamura T.
Published: April 2003

In a search for a human sequence related to a recently identified type I cytokine receptor δ1, which turned out to be a receptor subunit for a cytokine called TSLP, we have now identified a novel human type I cytokine receptor from a human T lymphocyte cDNA library. The deduced amino acid sequence of 371 residues has a typical signal sequence and a membrane-spanning region. The mature protein is predicted to have a molecular mass of 39,698 Da. The N-terminal extracellular region contains two fibronectin type III-like domains, four conserved cysteine residues, and a WSXWS box-like motif. The C-terminal intracellular region contains box 1 and box 2-like motifs. Thus, it has common characteristics of type I cytokine receptor family members, and we tentatively termed this protein CRLF2, which stands for cytokine receptor-like factor 2. Northern blot analysis revealed CRLF2 mRNA in liver, kidney, heart, and skeletal muscle. The fetal liver also expresses CRLF2 transcripts. The gene for CRLF2 was mapped to the pseudoautosomal region, Xp22.3 and Yp11.3 by FISH analysis, a region where genes encoding the IL-3 receptor α and the GM-CSF receptor α chains are also located. The biological function of this newly identified receptor is now under investigation.
Mapping of the rat glypican genes
Authors: Szpirer C. , Szpirer J. , Rivière M. , van Vooren P. , Veugelers M. , David G.
Published: April 2003

The glypicans compose a family of glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycans that play a role in the control of cell division and growth regulation. So far, six members (GPC1–6) of this family are known in vertebrates. The rat glypican gene 3 (Gpc3) was previously assigned to chromosome Xq36 (Shen et al., 1997). Using standard and radiation cell hybrids, we localized the five other rat glypican genes.
Assignment of T cell receptor (TCR) alpha-chain gene (A), beta-chain gene (B), gamma-chain gene (G), and delta-chain gene (D) loci on swine chromosomes by in situ hybridization and radiation hybrid mapping
Authors: Hiraiwa H. , Uenishi H. , Kiuchi S. , Watanabe M. , Takagaki Y. , Yasue H.
Published: April 2003

Using the cDNA sequence of porcine T-cell receptor (TCR) α-, β-, γ-, and δ-chain genes, we screened a porcine BAC library to isolate clones containing these genes. The isolated BAC clones were confirmed to carry these TCR genes by partial nucleotide sequencing. Among the clones obtained in the present screening, two clones carried both the TCR α-chain gene (TRA) and the TCR δ-chain gene (TRD) while one clone each carried only the sequence of either TRA or TRD. This observation demonstrated that TRA and TRD are localized in close proximity on a swine chromosome. Also two clones contained the sequence of the TCR β-chain gene (TRB), and two clones contained the sequence of TCR γ-chain gene (TRG). Fluorescence in situ hybridization using the above BAC clones as probes revealed that TRA and TRD, TRB, and TRG loci reside on swine chromosomes 7q15.3→q21, 18q11.3→q12, and 9q21→q22, respectively. The chromosome positions of TRA and TRB are consistent with those determined by somatic cell hybrid analysis (Rettenberger et al., 1996). In addition, RH mapping of these genes was performed using the INRA-University of Minnesota RH panel DNA. The result confirmed the position of TRA and TRB reported earlier (http://imprh.toulouse.inra.fr/), and further demonstrated that TRG was located 11 cR away from genetic marker SW989 toward the marker S0019.
Chromosomal distribution of the telomere sequence (TTAGGG)n in the Equidae
Authors: Lear T.L.
Published: April 2003

Telomeres are a class of repetitive DNA sequences that are located at chromosome termini and that act to stabilize the chromosome ends. The rapid karyotypic evolution of the genus Equus has given rise to ten taxa, all with different diploid chromosome numbers. Using fluorescence in situ hybridization (FISH) we localized the mammalian telomere sequence, (TTAGGG)n, to the chromosomes of nine equid taxa. TTAGGG signal was located at chromosome termini in all species, however additional signal was seen at interstitial sites on some chromosomes in the Burchell’s zebra, Equus quagga burchelli, the Hartmann’s zebra, Equus zebra hartmannae, and at large heterochromatin-associated regions on the chromosomes of the donkey, Equus asinus. The interstitial signal in the zebras may be a relic of an ancient telomere-telomere fusion and mark the point at which two ancestral chromosomes may have fused. For the donkey, the heterochromatin-associated signal may represent degenerate telomere-like satellite sequences and identify a second type of satellite DNA for this taxon.
Prothymosin α, a mammalian c-myc-regulated acidic nuclear protein, provokes the decondensation of human chromosomes in vitro
Authors: Boán F. , Viñas A. , Buceta M. , Domínguez F. , Sánchez L. , Gómez-Márquez J.
Published: April 2003

Prothymosin (ProTα) is an acidic nuclear protein, widely distributed in mammalian cells, whose expression is regulated by c-myc and linked to cell proliferation. ProTα interacts with histone H1 via its acidic domain, and its overexpression provokes the unfolding of chromatin fibers. Here we show that incubation of human native metaphase chromosomes with ProTα induces their extensive unravelling suggesting a function of this protein in chromosome decondensation.
Genomic imbalances in 61 renal cancers from the proximal tubulus detected by comparative genomic hybridization
Authors: Reutzel D. , Mende M. , Naumann S. , Störkel S. , Brenner W. , Zabel B. , Decker J.
Published: April 2003

Comparative genomic hybridization (CGH) has been applied to characterize 61 primary renal cell carcinomas derived histogenetically from the proximal tubulus. The tumor samples comprised 46 clear-cell renal cell carcinomas (ccRCCs) and 15 papillary renal cell carcinomas (pRCCs). Changes in the copy number of entire chromosomes or subregions were detected in 56 tumors (92%). In ccRCCs, losses of chromosome 3 or 3p (63%); 14q (30%); 9 (26%); 1 and 6 or 6q (17% each); 4 and 8 or 8p (15% each); 22 (11%); 2 or 2q and 19 (9% each); 7q, 10, 16, 17p, 18, and Y (7% each); and 5, 11, 13, 15, and 21 (4% each) were detected. Most frequent genomic gains in ccRCC were found on chromosome 5 (63%); 7 (35%); 1 or 1q (33%); 2q (24%); 8 or 8q, 12, and 20 (20% each); 3q (17%); 16 (15%); 19 (13%); 6 and 17 or 17q (11% each); and 4, 10, 11, 21, and Y (9% each). In pRCCs, gains in the copy number of chromosomes 7 and 17 (7/15, each) and 16 and 20 (6/15, each) were frequent. One pRCC showed amplification of subchromosome regions 2q22→q33, 16q, 17q and the entire X chromosome. In pRCC, losses were less frequently seen than gains. Losses of chromosomes 1, 14, 15, and Y (3/15 each) and 2, 4, 6, and 13 (2/15 each) were observed. In ccRCCs, statistical evaluation revealed significant correlations of chromosomal imbalances with tumor stage and grade, i.e., a gain in copy number of chromosome 5 correlated positively with low tumor grade, whereas a gain of chromosomes 10 and 17 correlated positively with high tumor grade. Furthermore, loss of chromosome 4 correlated positively with high tumor stage.
Heavenly Talk: Discourse, Artifacts, and Children’s Understanding of Elementary Astronomy
Authors: Schoultz Jan , Säljö Roger , Wyndhamn Jan
Published: April 2003

In the literature on children’s understanding of astronomical concepts, such as the shape of the earth and gravitation, the difficulties that children have in conceptualizing these phenomena have been documented in many studies. The purpose of this research is to critically scrutinize these findings by taking a situated and discursive perspective on reasoning (and cognitive development). Instead of viewing understanding as the overt expression of underlying mental models, children’s responses in interview studies should be regarded as situated and as dependent on the tools available as resources for reasoning. By modifying the interview situation through the introduction of a globe as a tool for thinking, the outcomes are radically different from those reported earlier. None of the problems that have been reported, where children, for instance, claim that people can fall off the earth, can be detected. Even among the youngest participants gravitation is often invoked as an explanatory concept. It is argued that the globe in this case serves as an efficient prosthetic device for thinking, and this illustrates the tool-dependent nature of human reasoning.
Nitric Oxide-cGMP and Prostacyclin-cAMP Pathways in Patients with Type II Diabetes and Different Types of Retinopathy
Authors: De La Cruz J.P. , Moreno A. , Guerrero A. , Ortega G. , González-Correa J.A. , Sánchez de la Cuesta F.
Published: April 2003

The aim of this study was to investigate two factors of endothelial dysfunction and their platelet second messengers in patients with type II diabetes and different types of retinopathy. We compared 20 healthy volunteers and 117 patients with type II diabetes (34 with no signs of diabetic retinopathy, 26 with background diabetic retinopathy, 29 with ischemic-proliferative diabetic retinopathy and 28 with edematous diabetic retinopathy). The following parameters were recorded: platelet aggregometry, nitrites, 6-keto-prostaglandin-F1α and intraplatelet cAMP and cGMP. Platelet aggregation was greater in patients with diabetic retinopathy. The concentration of ADP that produced 50% maximum intensity of aggregation was 1.81 µM in patients without diabetic retinopathy, 0.92 µM in patients with background diabetic retinopathy, 0.85 µM in patients with ischemic-proliferative diabetic retinopathy and 0.44 µM in patients with edematous diabetic retinopathy. The platelets in these patients were more resistant to inhibition by SIN-1 (concentrations of SIN-1 that produced 50% inhibition of maximum intensity of collagen-induced aggregation in the four patient groups: 18.1, 13.6, 16.2 and 33.2 µM, respectively). Nitrite concentration in patients with ischemic-proliferative diabetic retinopathy was one sixth of the value in healthy controls, but there was no significant difference between the control group and patients with edematous diabetic retinopathy. In the latter group, neutrophils increased nitrite production by 68.7 ± 3%, whereas in patients with ischemic-proliferative diabetic retinopathy, this increase was 18.7 ± 2.0%. We conclude that nitric oxide production is higher in patients with type II diabetes and edematous retinopathy than in those with ischemic-proliferative retinopathy. This finding, together with the possibly greater production of free radicals, may explain the greater impairment of platelet function in the former patients.
The Evidence behind Inhibitor Treatment with Recombinant Factor VIIa
Authors: Ludlam Christopher A.
Published: April 2003

Over the past 10 years considerable use has been made of recombinant factor VIIa (rFVIIa) for the treatment of patients with inhibitors to coagulation factors. During this time, its place in the management of acute bleeds and surgery has become better defined. Although pharmacokinetic studies report the half-life of rFVIIa as 2.7 h, there is considerable intersubject variability. Moreover, rFVIIa is cleared more rapidly in children than in adults. Assays for the measurement of rFVIIa plasma levels are not readily available in clinical diagnostic laboratories, although there is evidence that plasma FVII:C levels, measured by a one-stage prothombin-based assay, reflect the plasma concentration of rFVIIa:C. The level of FVII:C required to achieve haemostasis in different clinical circumstances remains uncertain. In order to overcome the logistic difficulties of repeated frequent bolus injections, and potentially to minimise usage, administration of rFVIIa by continuous infusion has been reported. However, there is some uncertainty as to whether continuous infusion of rFVIIa has similar therapeutic efficacy to an equivalent total dose administered by bolus injections. The extensive clinical experience with rFVIIa in haemophilic patients with inhibitors has been recorded in descriptive accounts of the Compassionate Use Programme and the Emergency Use Study. On the basis of the apparent clinical efficacy and safety reported in these studies, prospective randomised trials of different dose regimens have been undertaken for the treatment of acute bleeds and surgery. These have helped to define the minimum dose needed to achieve haemostasis. There remains considerable uncertainty about the minimal effective dose and appropriate duration of therapy in different clinical circumstances. There is therefore a need for the development of evidence-based guidelines for the use of rFVIIa in bolus and continuous infusion regimens in different settings, and for the therapeutic value of measuring plasma concentrations of rFVIIa, to facilitate the optimal use of this product. Furthermore, additional randomised clinical trials will help ensure that rFVIIa is used in the most clinically and cost effective way.
Treatment of Bleeding in Patients with Platelet Disorders: Is There a Place for Recombinant Factor VIIa?
Authors: Laurian Yves
Published: April 2003

The mechanism of action of recombinant factor VIIa (rFVIIa), i.e. increased thrombin generation on the membrane of activated platelets, as well as the results from in vitro and ex vivo models of thrombocytopenia or inherited thrombocytopathia may support some potential of rFVIIa in thrombocytopenia/thrombocytopathia. rFVIIa was reported as effective to stop or to decrease bleeding in few patients with severe thrombocytopenia resistant to platelet transfusions; however data are still scarce and clinical studies are really needed to define efficacy/safety ratio as well as optimal treatment regimen in this potential indication. Some data in patients with Glanzmann thrombasthenia (GT) may support the use of rFVIIa outside its primary indication in the cases in which there is no real treatment alternative (GT patients with antibodies to GP IIb-IIIa or with platelet refractoriness).
Sex Hormone Receptors Are Present in the Human Suprachiasmatic Nucleus
Authors: Kruijver Frank P.M. , Swaab Dick F.
Published: April 2003

The suprachiasmatic nucleus (SCN) is the clock of the brain that orchestrates circadian and circannual biological rhythms, such as the rhythms of hormones, body temperature, sleep and mood. These rhythms are frequently disturbed in menopause and even more so in dementia and can be restored in postmenopausal women by sex hormone replacement therapy (SHRT). Although it seems clear, both from clinical and experimental studies, that sex hormones influence circadian rhythms, it is not known whether this is by a direct or an indirect effect on the SCN. Therefore, using immunocytochemistry in the present study, we investigated whether the human SCN expresses sex hormone receptors in 5 premenopausal women and 5 young men. SCN neurons appeared to contain estrogen receptor-α (ERα), estrogen receptor-β (ERβ) and progesterone receptors. Median ratings of ER immunoreactivity per individual and per gender group revealed a statistically significantly stronger nuclear ERα expression pattern in female SCN neurons (p < 0.05). No significant sexual dimorphic tendency was observed for nuclear ERβ (p > 0.1) and progesterone receptors (p > 0.7). These data seem to support previously reported functional and structural SCN differences in relation to sex and sexual orientation and indicate for the first time that estrogen and progesterone may act directly on neurons of the human biological clock. In addition, the present findings provide a potential neuroendocrine mechanism by which SHRT can act to improve or restore SCN-related rhythm disturbances, such as body temperature, sleep and mood.
Mechanisms of TGF-β-Induced Cell Cycle Arrest
Authors: Hocevar Barbara A. , Howe Philip H.
Published: April 2003

Mitogenic growth factors stimulate cell growth by initiating a signaling cascade leading to the activation of the cyclin-dependent kinases (cdks), phosphorylation of pRb, and subsequent entry of the cell into the S phase. Transforming growth factor-β (TGF-β) is a potent antimitogen in a wide variety of cells and is postulated to inhibit cell cycle progression by blocking the late G1 activation of the cdks, thereby preventing pRb phosphorylation and S phase entry. The loss of TGF-β sensitivity in many transformed cells coupled with recent data demonstrating a deregulation of cyclins, cdks, and cdk inhibitors in many types of cancer has attracted much attention to the molecular mechanism of TGF-β-mediated growth arrest. Despite these recent advances, further research is required to elucidate how these effects of TGF-β on the cyclins, cdks, and cdk inhibitors are linked to the TGF-β receptor complex and the Smad proteins.
Relationship between Whole-Body Protein Turnover and Serum Creatinine in Chronically Uremic Patients
Authors: Biolo Gianni , Toigo Gabriele , Ciocchi Beniamino , Morena Gianpaolo , Situlin Roberta , Vasile Alfonso , Carraro Michele , Faccini Luigi , Guarnieri Gianfranco
Published: April 2003

To investigate the relationship between decline in renal function and alterations of protein metabolism we determined the rate of whole-body protein turnover in a group of 15 postabsorptive chronically uremic patients (9 males and 6 females) with different levels of serum creatinine concentrations (average 5.7 ± 0.4 (SE) mg·dl–1; range 3.3–9.1). Patients’ age and body mass index were 53 ± 4 years (range 26–73) and 24.7 ± 0.6 kg/m2 (range 20.3–28.7), respectively. Nutritional status (plasma albumin 3.6 ± 0.4 g·dl–1) and acid-base equilibrium (arterial pH 7.38 ± 0.01) were fairly controlled by therapy. Whole-body leucine rate of appearance (Ra), an index of whole-body protein turnover, was assessed using a stable isotope technique. L-[1-13C]leucine was continuously infused and plasma [1-13C]α-ketoisocaproic acid enrichment was determined in steady-state conditions as a marker of the intracellular leucine enrichment. The average leucine Ra was 2.03 ± 0.13 µmol·kg–1·min–1 (range 1.29–3.19). Using simple linear regression analysis, the coefficient of correlation between the individual values of serum creatinine concentration and leucine Ra was 0.59 (n = 15; p = 0.02). Leucine Ra did not significantly correlate with blood pH or plasma albumin. In conclusion, we found a positive linear relationship between the values of plasma creatinine concentration and the rate of whole-body protein degradation. This correlation suggests that the progression of renal insufficiency is associated with accelerated rates of turnover of body proteins.
In vivo Repeatability and Reproducibility of the Quantitative Light-Induced Fluorescence Method
Authors: Tranæus Sofia , Shi Xie-Qi , Lindgren Lars-Erik , Trollsås Karin , Angmar-Månsson Birgit
Published: April 2003

In vivo repeatability and reproducibility of the quantitative light-induced fluorescence (QLF) method were tested with respect to three variables: lesion area, and average and maximum changes in lesion fluorescence. To test the image-capturing stages, three analysts each captured images of 15 incipient smooth surface lesions in vivo, and the images were analysed by one of the analysts. To test the analytical stage of the method, three analysts analysed the images of 15 in vivo incipient smooth surface lesions. For the image-capturing stage, inter-examiner reliability showed an intra-class correlation coefficient (r) between 0.95 and 0.98. For the analytical stage, intra-examiner reliability for all three analysts showed a value of r between 0.93 and 0.99. Inter-examiner reliability showed a value of r between 0.95 and 0.99. It was concluded that the in vivo repeatability and reproducibility of the QLF method are excellent.
Light-Induced Fluorescence Studies on Dehydration of Incipient Enamel Lesions
Authors: Al-Khateeb S. , Exterkate R.A.M. , de Josselin de Jong E. , Angmar-Månsson B. , ten Cate J.M.
Published: April 2003

Changes in the hydration state of enamel affect its optical qualities, such as light scattering and fluorescence. In this study, the rate of fluorescence loss was measured when incipient enamel lesions with different de-remineralization history were left to dehydrate. Four groups of lesions were studied. In groups A, B and C, the lesions were prepared in vitro in an acid-gel system. Group A was kept as control, and groups B and C were remineralized (4 weeks) without and with 1 ppm F in solution, respectively. Group D consisted of natural incipient lesions. Enamel fluorescence was measured for all lesions immediately after removal from water and subsequently at short intervals for 30 min. The change in fluorescence with dehydration varied between the groups. In lesions from groups A and B, it followed a double exponential decrease, while in lesions from groups C and D, it followed a mono-exponential decrease. In all groups, the fluorescence of sound surfaces declined mono-exponentially. The ‘fractional fluorescence difference’, defined as (Lsound – Lcarious )/Lsound, became constant after periods of dehydration of about 5, 5, 20 and 5 min for groups A to D, respectively. The observation of the change of fluorescence with dehydration should be taken into consideration when planning studies that use fluorescence as an assessment method. However, it might also be used to gain insight into the properties for fluid transport inside the various lesions, relevant to de-remineralization or fluoride treatments.
Effect of a Triclosan-Containing Toothpaste Supplemented with 10% Xylitol on Mutans Streptococci in Saliva and Dental Plaque
Authors: Jannesson L. , Renvert S. , Kjellsdotter P. , Gaffar A. , Nabi N. , Birkhed D.
Published: April 2003

The aim of the present investigation was to evaluate the effect of the combination of triclosan and xylitol in toothpaste on mutans streptococci (MS) in saliva and dental plaque. 155 individuals with >105 MS/ml saliva were included in a 6-month double-blind clinical study. They were divided into three groups (n = 51–52) balanced according to their MS counts at baseline. Each group used one of the following types of dentifrice: (1) Colgate Total© with the addition of 10% xylitol (Total-Xylitol), (2) Colgate© Total and (3) Colgate Total© without triclosan and without xylitol. Whole saliva and pooled plaque samples were obtained after 2, 4 and 6 months. When comparing the MS counts within the groups for saliva and plaque samples, Total-Xylitol showed significant reduction at all three sampling occasions (p < 0.001). Mean reduction at the 6-month sample for saliva was 0.81/ml and for plaque 0.89 per sample (log values). ANOVA revealed significant differences between Total-Xylitol and the two other products at 6 months for MS in saliva and dental plaque. The conclusion from this 6- month study is that the addition of 10% xylitol to a triclosan-containing dentifrice reduces the number of MS in saliva and dental plaque.
Solute-Free versus Electrolyte-Free Water Clearance in the Analysis of Osmoregulation
Authors: Shimizu Kurakazu , Kurosawa Takeshi , Sanjo Teizo , Hoshino Masanobu , Nonaka Tatsuya
Published: April 2003

Background: Although attention has recently focused on electrolyte-free water clearance (E-CH2O) as a replacement for solute-free water clearance (CH2O), especially from the viewpoint of plasma sodium regulation, a thorough comparison of the two has yet to be conducted. Methods: CH2O and E-CH2O were systematically compared in normal subjects in different diuretic stages, including furosemide-induced solute diuresis, and in patients with renal disease. Results: The normal renal ability to conserve free water based on E-CH2O was only 41% of that based on CH2O. E-CH2O remained positive until the urinary osmolality exceeded 500 mosm/kg H2O, markedly different from the 300 mosm/kg H2O for CH2O. The difference between E-CH2O and CH2O could ultimately be attributed to urea osmolar clearance, i.e., urea excretion rate/plasma osmolality, which accounted for about 40% of the osmolar clearance. CH2O underestimated the free water clearance by about 1 ml/min on average at all diuretic stages. Conclusions: E-CH2O is a more correct parameter than CH2O with regard to the regulation of both plasma sodium and plasma osmolality. However, there is the opinion that the concept of E-CH2O is difficult to understand and that E-CH2O is still not a generally accepted parameter. It is expected that the results of the present study will lead to more general acceptance.
Impact of Thalassemia major on Patients and Their Families
Authors: Caro J. Jaime , Ward Alexandra , Green Traci Craig , Huybrechts Krista , Arana Alejandro , Wait Suzanne , Eleftheriou Androulla
Published: April 2003

Objective: To describe the burden of thalassemia major and its treatment, in terms of prevalence of iron-overload-related complications, direct and indirect costs, and the patient’s physical and social well-being. Methods: From October 1999 to May 2000 a survey of patients with thalassemia major was conducted in ten countries: Cyprus, Egypt, Greece, Hong Kong, India, Iran, Italy, Jordan, Taiwan, and the United States. Results: 1,888 questionnaires (65%) were returned. The responses suggest that nowadays patients begin blood transfusions, and most use desferrioxamine (84.8%), but iron-related complications, including life-threatening ones such as heart disease, are still common. Conclusions: There remains a need to improve the management of thalassemia, as many patients with iron-related complications experience physical and social limitations.
Hungarian Cancer Mortality and Food Availability Data in the Last Four Decades of the 20th Century
Authors: Rodler I. , Zajkás G.
Published: April 2003

Objective: To identify the dietary risk factors present in the nutrition of the Hungarian population. Method: We evaluated Hungarian cancer mortality data, and carried out a comparative analysis of the Hungarian National Food Balance Sheets (food availability) and dietary surveys (energy and nutrient intake). Results: The cancer mortality rate in Hungary is the highest in Europe and an analysis of the past 40 years has revealed a worsening trend. Assessment of the Hungarian dietary pattern suggests that the high fat intake could be a possible risk factor in the development of lung, colon, rectum, female breast and prostate cancer. The availability of fats in Hungary was found to be the highest in a European comparison in the second half of the 1990s, while the average fat energy percentage in the diet of the male and female population was 38.0% (SD 5.7) between 1992 and 1994. Apart from the high fat consumption, the insufficient intake of vegetables and fruits could be identified as a major, convincing risk factor present in the nutrition of Hungarians, and plays a role in the development of mouth and pharynx, esophagus, lung, stomach, colon and rectum cancers, and is a probable risk factor in the development of pancreatic tumors. The availability of vegetables and fruits in the Hungarian population is one of the lowest in Europe and, in addition, the intake of dietary fiber, carotenoids, and ascorbic acid is also inadequate. Conclusion: Hungary has the highest cancer mortality rate in Europe, and the death rate associated with this disease is increasing. Our analysis of food balance sheets and dietary survey data clearly demonstrate the presence of certain known dietary risk factors in the nutrition of the Hungarian population.
The Neurophysiology of Auditory Perception: From Single Units to Evoked Potentials
Authors: Eggermont Jos J. , Ponton Curtis W.
Published: April 2003

Evoked electric potential and magnetic field studies have the immense benefit that they can be conducted in awake, behaving humans and can be directly correlated with aspects of perception. As such, they are powerful objective indicators of perceptual properties. However, given a set of evoked potential and/or evoked field waveforms and their source locations, obtained for an exhaustive set of stimuli and stimulus contrasts, is it possible to determine blindly, i.e. predict, what the stimuli or stimulus contrasts were? If this can be done with some success, then a useful amount of information resides in scalp-recorded activity for, e.g., the study of auditory speech processing. In this review, we compare neural representations based on single-unit and evoked response activity for vowels and consonant-vowel phonemes with distinctions in formant glides and voice onset time. We conclude that temporal aspects of evoked responses can track some of the dominant response features present in single-unit activity. However, N1 morphology does not reliably predict phonetic identification of stimuli varying in voice onset time, and the reported appearance of a double-peak onset response in aggregate recordings from the auditory cortex does not indicate a cortical correlate of the perception of voicelessness. This suggests that temporal aspects of single-unit population activity are likely not inclusive enough for representation of categorical perception boundaries. In contrast to population activity based on single-unit recording, the ability to accurately localize the sources of scalp-evoked activity is one of the bottlenecks in obtaining an accessible neurophysiological substrate of perception. Attaining this is one of the requisites to arrive at the prospect of blind determination of stimuli on the basis of evoked responses. At the current sophistication level of recording and analysis, evoked responses remain in the realm of extremely sensitive objective indicators of stimulus change or stimulus differences. As such, they are signs of perceptual activity, but not comprehensive representations thereof.
Nongenomic Effects of Corticosteroids on Ion Transport by Stria vascularis
Authors: Lee Jun Ho , Marcus Daniel C.
Published: April 2003

Stria vascularis electrogenically secretes potassium into endolymph and this secretion is known to be under acute control of several hormone receptors including purinergic, adrenergic and muscarinic receptors. Recently, chronic application of glucocorticosteroid hormones in autoimmune mice was reported to restore both hearing and normal strial morphology. The purpose of this study was to investigate the acute nongenomic effects of glucocorticoids and mineralocorticoid on the short circuit current (Isc,probe) across isolated stria vascularis of gerbils using the voltage-sensitive vibrating probe. Application of prednisolone (0.1–30 µM) caused an increase of Isc,probe in a dose-dependent manner with an EC50 of 1.1 ± 0.2 µM (n = 5). Hydrocortisone (10 µM, n = 5) and dexamethasone (10 µM, n = 5) also increased Isc,probe, but the response was transient and the response rate was faster than for prednisolone. By contrast, aldosterone (10 µM, n = 6) caused a transient decrease of Isc,probe within seconds. These results suggest that prednisolone increased secretion of K+ via a nongenomic mechanism in the range of therapeutic plasma concentrations and that this stimulatory effect of glucocorticoids is specific since the mineralocorticoid aldosterone caused a distinctly different response.
Comparison of the BBL-Mycobacteria Growth Indicator Tube Method with Culture in the Diagnosis of Tuberculosis and Evaluation of the Resistance Patterns of Isolated Strains to Four Major Drugs
Authors: Kocazeybek Bekir Sami
Published: April 2003

The BBL-mycobacteria growth indicator tube system (MGIT) is used for a rapid detection of the presence of mycobacteria. Our study aimed to compare MGIT with the Löwenstein-Jensen (LJ) reference method in clinical samples with suspected pulmonary and extrapulmonary tuberculosis, and to evaluate the primary and secondary resistance patterns by determining the resistances of the isolated strains to four major antimycobacterial drugs. 648 clinical samples from different clinics, with suspected pulmonary or extrapulmonary tuberculosis based on clinical, radiological, histopathological and immunological findings, were included in the investigation. The samples were first stained with Ziehl-Neelsen (ZN) and then cultured in LJ medium according to the standard bacteriological procedure and in the MGIT as recommended by the manufacturer. Conventional biochemical tests and p-nitro-alpha-acethylamino-beta-hydroxypropiophene of the Bactec system were used to identify the isolated mycobacterial strains. The susceptibilities to streptomycin, isoniazid, rifampicin, ethambutol were tested by the BBL-MGIT antibiotic susceptibility test and the resistances of the strains found to be resistant to any of the drugs were confirmed by the agar proportion method. Mycobacterium spp. were isolated in 61 (9.4%) out of 648 samples. Eventually, 58 out of 61 strains were classified as Mycobacterium tuberculosis and the other 3 as Mycobacterium tuberculosis complex. 32 of these were ZN positive. The growth time was determined as 12.2 days by the MGIT method and 24.1 days by the LJ method (p < 0.001). 29 strains were ZN negative. Their growth time was 23 days by the MGIT method and 37 days by the LJ method (p < 0.001). Drug resistance was detected in 23 (37.7%) of 61 cases (of whom 39 were new and 22 were former patients); of these resistances, 8 (20.51%) were primary and 15 (68.18%) were secondary. In double drug resistance, secondary resistance was found only to isoniazid + rifampin (4 cases) whereas both primary and secondary resistances were found to one drug. The highest cumulative drug resistance – both primary and secondary – was found to isoniazid. In conclusion, the MGIT was found to be advantageous because it enables rapid bacterial identification of tuberculosis and detection of antimicrobial resistance due to its high sensitivity and specificity. It is quicker than the LJ method. Its antibiotic susceptibility can be tested and it is easy to perform. We recommend to include it in routine laboratory work. In addition, our study suggests that the high ratio of secondary resistance in the public might be related to inappropriate and insufficient treatment of tuberculosis, and noncompliance, which appear to cause an important increase in primary tuberculosis as a result of new contaminations.
Pericarditis due to Anaerobic Bacteria
Authors: Brook Itzhak
Published: April 2003

This review describes the microbiology, diagnosis and management of pericarditis due to anaerobic bacteria. The predominant anaerobes recovered from patients with pericarditis were: gram-negative bacilli (mostly of the Bacteroides fragilis group), anaerobic streptococci, Clostridium spp., Fusobacterium spp., and Bifidobacterium spp. Anaerobic bacteria can be isolated in pericarditis resulting from the following mechanisms: (1) spread from a contiguous focus of infection, either de novo or after surgery or trauma (pleuropulmonary, esophageal fistula or perforation, and odontogenic); (2) spread from a focus of infection within the heart, most commonly from endocarditis; (3) hematogenous infection, and (4) direct inoculation as a result of a penetrating injury or cardiothoracic surgery. No differences were found in the clinical diagnostic features between cases of pericarditis due to anaerobic bacteria and those due to aerobic and facultative bacteria. Anaerobic gram-negative bacilli have increased their resistance to penicillins and other antimicrobials in the last decade. Complete identification and testing for antimicrobial susceptibility and lactamase production are therefore essential for the management of infections caused by these bacteria. Treatment of pericarditis involving anaerobic bacteria includes the use of antibiotic therapy effective against these organisms.
Sildenafil in the Cardiologist’s Office: Patients’ Attitudes and Physicians’ Practices toward Discussions about Sexual Functioning
Authors: Bedell Susanna E. , Graboys Thomas B. , Duperval Melissa , Goldberg Robert
Published: April 2003

Sildenafil is a medication increasingly prescribed to improve sexual function in patients who have erectile dysfunction. Because a major contraindication to the use of sildenafil is a history of coronary disease and the concomitant use of nitrates, it becomes increasingly important for cardiologists to prescribe this medication. We evaluated the nature of discussions in all 70 patients for whom sildenafil was prescribed in a cardiology practice between April and July 1998. We used a standardized questionnaire to determine the patients’ perspective on the sexual history and the extent to which they wanted their physicians to take a detailed history about sexuality. A separate chart review evaluated the nature of physicians’ discussions about sexual functioning before sildenafil was prescribed. Fifty-five of the 70 patients (79%) responded to the survey. The majority of patients (98%) felt that physicians should talk with patients about sexual functioning. However, only 73% of patients believed their doctor was comfortable talking with them about this subject. Sixty percent of patients reported that their doctor had ever talked with them about erectile function and only 15% had ever had a discussion with their doctors about specific difficulties during intercourse. Based on the results of the chart review, only 24% of the patients ever specifically discussed the used of sildenafil with their physician prior to the time that it was prescribed. The results of the study suggest that patients with coronary disease erectile dysfunction are comfortable talking with their physicians about sexual functioning, but these conversations occur infrequently.
Is the Site of Thrombus Formation in the Left Atrial Appendage Associated with the Risk of Cerebral Embolism?
Authors: Yamaji Kunihiro , Fujimoto Shinichi , Yutani Chikao , Hashimoto Toshio , Nakamura Shinobu
Published: April 2003

Atrial fibrillation (AF) is a risk factor for cerebral embolism, with the left atrial appendage (LAA) being considered as the source of emboli. However, the relationship between the histologic properties of LAA thrombi and the occurrence of cerebral embolism is not known. Seventy-six hearts from patients who died within 1 month after cerebral embolism were studied at autopsy. Patients were grouped according to the presence of AF and the presence of valvular disease (VD). We determined whether the LAA thrombi adhered to the trabecular region or the remainder of the LAA. LAA thrombi were grouped into three stages: a fresh stage in which thrombi consisted of fibrin and platelets, an organizing stage in which angiogenesis was observed in the thrombi, and an organized stage in which endothelial cells covered the surface of the thrombi. The AF+/VD– group included 19 patients (25.0%), the AF+/VD+ group 8 (10.5%), the AF–/ VD– group 37 (48.7%), and the AF–/VD+ group included 12 patients (15.8%). LAA thrombi were observed in 15 patients (78.9%) in the AF+/VD– group, and all of the thrombi adhered to the trabecular region. Thrombi in the fresh and the organizing stages were observed in 10 patients (66.7%). Patients in the AF+/VD– group accounted for about 25% of the cases of cerebral embolism. All of these thrombi were attached to the trabecular region, and about 70% of them could represent an embolic source.
Obstructive Jaundice Alters CD44 Expression in Rat Small Intestine
Authors: Sheen-Chen Shyr-Ming , Ho Hsin-Tsung , Chen Wei-Jen , Eng Hock-Liew , Wu Chih-Hsiung
Published: April 2003

Hypothesis: CD44 is an adhesion molecule expressed by neutrophils, lymphocytes and epithelial cells. CD44 is involved in cell-cell and cell-matrix binding. In addition to lymphocyte trafficking, CD44 also plays a crucial role in the maintenance of intestinal villus integrity. We hypothesize that obstructive jaundice may alter CD44 expression in the rat small intestine and oral glutamine intake can restore the altered CD44 expression in the small intestine of the rat undergoing obstructive jaundice. Materials and Methods: In a prospective animal model study at a university hospital, 41 Sprague-Dawley rats were randomized to 4 groups. Group A (n = 13, control) underwent a sham operation. Group B (n = 12, obstructive jaundice for 1 week) underwent common bile duct ligation. Group C (n = 8, obstructive jaundice for 2 weeks) underwent common bile duct ligation. Group D (n = 8, obstructive jaundice for 2 weeks) underwent common bile duct ligation with oral glutamine intake daily. After 1 and 2 weeks, segments of the proximal jejunum and distal ileum were harvested from groups A and B and groups C and D, respectively. Immunohistochemical expression of CD44 on the cell surface was then evaluated and recorded. Comparisons among the 4 groups were performed. Results: In the 1-week obstructive jaundice group, 173.8 ± 24.0 cells/1,000 enterocytes of the proximal jejunum expressed surface CD44, while 137.0 ± 13.8 cells were stained in the control group (p < 0.001). In the 1-week obstructive jaundice group, 169.8 ± 20.7 cells/1,000 enterocytes of the distal ileum expressed surface CD44, while 119.5 ± 20.8 cells were stained in the control group (p < 0.001). In the 2-week obstructive jaundice group, the number of cells expressing surface CD44 were significantly decreased both in jejunum (112.1 ± 17.0, p = 0.002) and ileum (100.1 ± 12.5, p = 0.028) when compared with those of the control group. With daily oral glutamine intake in group D, the number of cells expressing surface CD44 in the jejunum (149.3 ± 29.7) was restored to that of the control group (p = 0.302) and the number of cells expressing surface CD44 in the ileum (140.4 ± 23.0) was even higher than that of the control group  (p = 0.045). Conclusion: Obstructive jaundice for 1 week initially upgraded CD44 expression in the rat small intestine and the CD44 expression later became significantly depressed after obstructive jaundice for 2 weeks. Oral glutamine intake daily could effectively restore the CD44 expression in the small intestine of the rat undergoing obstructive jaundice for 2 weeks.
Clinical Study on the Antiseptic Effect of Povidone-Iodine Solution for the Surgical Field of Digestive Tract Operations
Authors: Shindo K. , Funai S. , Kuroda K. , Wakano T. , Nishimura K.
Published: April 2003

Our previous study showed 10% povidone-iodine solution (Isodine®) to be safe and effective for skin antisepsis in healthy young adults. The present study was carried out in 45 adult and old-age patients undergoing surgery (average age 62 years). 10% povidone-iodine solution was effective for skin antisepsis; however, after completion of the intra-abdominal procedures, contaminations were found due to the type II and IV operations with unprotected incision sites and wound walls. Diabetes was found to be one of the most important factors in surgical site infection. In conclusion, the antiseptic efficacy immediately after application of 10% povidone-iodine solution was evidenced in surgical patients with class II wounds. The solution was also effective for the prevention of postoperative skin wound infection.
The Importance of Disinfection Therapy Using Povidone-Iodine Solution in Atopic Dermatitis
Authors: Sugimoto Kazuo , Ishikawa Nobuyasu , Sugioka Tatuya , Koseki Hideaki , Kubosawa Hitoshi , Kagawa Shohei , Shimojo Naoki , Ito Shoichi , Hattori Takamichi
Published: April 2003

The combination of the local disinfection therapy against Staphylococcus aureus with the conventional therapy for atopic dermatitis has been widely used, and the improvement in skin lesions has been reported to be associated with a remarkable decrease in IgE levels and reagin antibody titers. We have already reported that affected organs were not only the skin but also the gastrointestinal tract in a case with atopic dermatitis. In the present study, the duodenal tissues were examined by biopsy in 32 patients with atopic dermatitis, and mild or chronic duodenitis was observed in all samples. Toxins were examined by PCR from 180 Staphylococcus aureus strains obtained from our patients. The detection rate of toxins was 82.8%. In many patients, antitoxin IgE antibody titers corresponding to their types of toxin and IgE levels were decreased in a parallel manner as time passed. We found 1 patient who complained of paresthesia in all four limbs, and her neurological and radiological examinations showed moderate cervical spondylosis. Neurological examinations revealed some abnormalities in 43 out of 50 patients with atopic dermatitis, such as hyperreflexia of the legs. Cervical MRI was carried out randomly and showed abnormal findings in 21 of 25 patients, in whom 18 duodenal tissues were examined by biopsies.