bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous activation and hepatocyte growth factor activator inhibitor 1-mediated inhibition of matriptase induced at activation foci in human mammary epithelial cells
Authors: Lee Ming-Shyue , Kiyomiya Ken-ichi , Benaud Christelle , Dickson Robert B. , Lin Chen-Yong
Published: March 2005

Activation of single-chain, latent matriptase, a type II transmembrane serine protease, depends on the weak proteolytic activity of its own zymogen as well as its cognate inhibitor, hepatocyte growth factor activator inhibitor 1 (HAI-1). Oligomerization of matriptase zymogens and HAI-1, and probably its interaction with other proteins, has been proposed to occur during matriptase activation. In the present study, we examined the cellular events associated with matriptase activation triggered either by the physiological inducer sphingosine 1-phosphate (S1P) or by a chemical inducer, the polyanionic compound suramin. S1P-induced matriptase translocation to cell-cell contacts, where it is activated, is an F-actin polymerization-dependent process. Conversely, suramin-induced matriptase accumulation and activation at vesicle-like structures is an F-actin polymerization-independent process. While matriptase activation can occur at different subcellular locations, both S1P- and suramin-induced matriptase accumulation form unique subcellular structures, termed activation foci, where oligomerization of matriptase zymogens and HAI-1 may occur, promoting matriptase activation. Furthermore, matriptase activation may be regulated by intracellular signaling, because Ro 31-8220, a bisindolylmaleimide protein kinase C inhibitor, inhibited both S1P- and suramin-induced activation. The requirement of HAI-1 for matriptase activation and the coincidence of HAI-1 and matriptase in activation foci apparently provide rapid access of HAI-1 for the inhibition of matriptase immediately after its activation. Indeed, all activated matriptase was detected in complexes with HAI-1 only 5 min after suramin stimulation. The close temporospatial coupling of matriptase activation with its inhibition suggests that the proteolytic activity of this enzyme must be well controlled and that the proteolysis of matriptase substrates may be tightly regulated by this mechanism.
Insulin-Like Growth Factor I Levels in Healthy Children
Authors: Clayton P.E. , Hall C.M.
Published: March 2005

Measurement of insulin-like growth factor I (IGF-I) levels is used during the assessment of a child for the presence of growth hormone (GH) deficiency and to monitor the efficacy of GH replacement therapy. In either case, robust normative data are required to allow IGF-I values to be expressed as standard deviation scores, enabling comparison between individuals and assessment of change over time. However, IGF-I levels in healthy children are affected by a number of parameters, including age, gender, pubertal status, height, nutrient intake, body composition, intercurrent illness and ethnicity, and the generation of such data requires the collection of samples from significant numbers of healthy children. As external quality assurance schemes for IGF-I and an international standard based on authentic recombinant IGF-I are not widely used, it is imperative for the clinician to understand the performance characteristics and limitations of the IGF-I assay used and to be aware of the source and quality of control data. It must also be recognized that IGF-I measurement is only one component of the diagnostic process and has its limitations, as tissue sensitivity to circulating serum IGF-I levels will differ between individuals.
Insulin-Like Growth Factors as Diagnostic Tools in Growth Hormone Deficiency during Childhood and Adolescence: The KIGS Experience
Authors: Ranke Michael B. , Schweizer Roland , Lindberg Anders , Price David A. , Reiter Edward O. , Albertsson-Wikland Kerstin , Darendeliler Feyza
Published: March 2005

Growth hormone (GH) deficiency in children covers a spectrum of disorders involving an impairment in GH secretion and a clinical syndrome characterized by permanent stunting of growth. Ascertaining impairments in GH secretion directly is complex, especially if GH deficiency (GHD) is isolated and not caused by congenital or acquired pituitary defects or genetic abnormalities. It has been established that the concentrations of GH-dependent peptides, such as insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3), are low in patients with GHD. Their levels are, however, also influenced by a multitude of factors, such as age, gender, height, liver function, nutritional status and other hormones. In addition, the type of complex formed, e.g. either binary or ternary, may influence the measurements of IGFs and their binding proteins. Therefore, levels of IGF-I and IGFBP-3 are generally lower in short children compared with age-matched norms. The reported diagnostic value of sub-normal basal levels of IGF-I and IGFBP-3 is, in terms of sensitivity and specificity, approximately 70%. Thus, definite proof of GHD can only be achieved by means of GH measurements. As the diagnosis of GHD is somewhat unlikely if IGF testing shows normal values, it is clearly advantageous to schedule these tests as part of the initial diagnostic work-up in short children, as their implementation is not only practical but also inexpensive. The Pfizer International Growth Database (KIGS) analysis of IGF-I (n = 2,750) and IGFBP-3 (n = 1,300) levels in children with idiopathic GHD shows that these two parameters are now firmly embedded in diagnostic strategies around the world.
Insulin-Like Growth Factor (IGF) Parameters and Tools for Efficacy: The IGF-I Generation Test in Children
Authors: Rosenfeld Ron G. , Buckway Caroline , Selva Karin , Pratt Kathie L. , Guevara-Aguirre Jaime
Published: March 2005

Serum levels of growth hormone (GH)-dependent peptides could provide important and valuable measures of GH sensitivity and, potentially, responsiveness. In normal individuals, serum insulin-like growth factor I (IGF-I) concentrations are dependent on the dose of GH given, with IGF-I responsiveness not decreasing with age. Individuals heterozygous for the E180 GH receptor (GHR) splice mutation have normal IGF-I generation, but those homozygous for the E180 splice mutation have very low basal and stimulated IGF-I concentrations. Similar results are observed for the serum IGF-binding protein 3 (IGFBP-3) response to GH, with a correlation between changes in serum concentrations of IGF-I and changes in IGFBP-3 in normal, heterozygotic, GH-insensitive and GH-deficient participants. In individuals with the E180 splice mutation, IGF-I and IGFBP-3 tests show sensitivity and specificity for detecting GH insensitivity (GHI). In children with idiopathic short stature, it appears that some individuals have selective resistance to GH, with their ability to generate IGF-I more impaired than their ability to generate other GH-dependent peptides. This heterogeneous group may require individualization of GH dosage. IGF generation tests remain the best short-term, in vivo test for classic GHI, although diagnostic tests will undoubtedly require further modification to identify milder pathophysiologic abnormalities.
Role of Insulin-Like Growth Factor Iin Maintaining Normal Glucose Homeostasis
Authors: Clemmons David R.
Published: March 2005

Insulin-like growth factor I (IGF-I) has significant structural homology with insulin. IGF-I has been shown to bind to insulin receptors to stimulate glucose transport in fat and muscle, to inhibit hepatic glucose output and to lower blood glucose while simultaneously suppressing insulin secretion. However, the precise role of IGF-I in maintaining normal glucose homeostasis and insulin sensitivity is not well defined. Studies in patients with diabetes have shown that in insulin-deficient states, serum IGF-I concentrations are low and increase with insulin therapy. Similarly, administration of insulin via the portal vein results in optimization of plasma IGF-I concentrations. A patient with an IGF1 gene deletion was shown to have severe insulin resistance that improved with IGF-I therapy. Studies conducted in experimental animals have shown that if IGF-I synthesis by the liver is deleted, the animals become insulin-resistant, and this is improved when IGF-I is administered. Likewise, deletion of the IGF-I receptor in muscle in mice induces severe insulin resistance. Administration of IGF-I to patients with type 2 diabetes mellitus has been shown to result in an improvement in insulin sensitivity and a reduction in the requirement for exogenously administered insulin to maintain glucose homeostasis. A polymorphism in the IGF1 gene that has been shown to reduce serum IGF-I results in an increased prevalence of type 2 diabetes. Taken together, these findings support the conclusion that IGF-I is necessary for normal insulin sensitivity, and impairment of IGF-I synthesis results in a worsening state of insulin resistance.
Acromegaly and Cancer
Authors: Jenkins Paul J.
Published: March 2005

In recent years, it has become increasingly recognized that acromegaly is associated with an increased prevalence of colorectal cancer and pre-malignant tubular adenomas. The aetiology of these tumours is unknown but is likely to reflect increased levels of both insulin-like growth factor I (IGF-I), which is implicated in the development of sporadic colorectal cancer, and environmental factors, such as the bile acid deoxycholic acid. There is also evidence to suggest that the prevalence of breast and perhaps haematological malignancies might be increased in acromegaly, although these associations have been based on mostly small epidemiological surveys and clarification will come in the future once large-scale epidemiological studies have been completed.
ICAM G241A Polymorphism and Soluble ICAM-1 Serum Levels: Evidence for an Active Immune Process in Schizophrenia
Authors: Krönig Holger , Riedel Michael , Schwarz Markus J. , Strassnig Martin , Möller Hans-Jürgen , Ackenheil Manfred , Müller Norbert
Published: March 2005

Objectives: We have previously reported reduced serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in schizophrenic patients. A single-nucleotide polymorphism (SNP) of the ICAM-1 gene was described at position 241. The G→A SNP results in a nonsynonymous amino acid exchange of the ICAM-1 protein, and the A allele was shown to be also associated with several immunological disorders like rheumatoid arthritis. Methods: We investigated 70 schizophrenic patients and 128 unrelated healthy control persons regarding the relationship between the serum levels of sICAM-1 and the ICAM-1 G214A polymorphism. Results: We were able to replicate our previous finding of reduced sICAM-1 levels in schizophrenia. Healthy control persons carrying the polymorphic A allele showed markedly lower sICAM-1 serum levels than carriers of the homozygous GG wild type (p < 0.004). In contrast, no significant difference in the sICAM-1 serum levels were seen regarding the G241A genotype distribution in schizophrenic patients. Conclusion: We hypothesize that the biochemical effect of the G241A SNP is masked in schizophrenic patients, indicating a disease-related mechanism leading to reduced levels of sICAM-1 in schizophrenia.
Tropical Pancreatitis
Authors: Tandon Rakesh K. , Garg Pramod K.
Published: March 2005

Tropical pancreatitis is a special type of chronic pancreatitis that is seen mainly in tropical countries. The prevalence of tropical pancreatitis is about 126/100,000 population in southern India. It occurs usually in young people, involves the main pancreatic duct and results in large ductal calculi. The etiology is not known, but genetic mutations such as the SPINK1 gene mutation and environmental factors are likely causes. Clinically, >90% of patients present with abdominal pain. About 25% of patients develop diabetes which generally requires insulin for its control but is ketosis-resistant. Painless diabetes is another clinical presentation in some patients. Most patients develop malnutrition during the course of the disease. Steatorrhea is less common. Patients with tropical pancreatitis may develop pancreatic cancer as a long-term complication. The diagnosis can be established by plain radiography of the abdomen, ultrasonography, computerized tomography scan of the abdomen or endoscopic retrograde cholangiopancreatography. Management is directed towards relief from pain and control of diabetes and steatorrhea. Pain relief can be obtained by analgesics and enzyme supplementation with preparations rich in proteases. Endotherapy coupled with stone fragmentation by extracorporeal shock wave lithotripsy is an effective therapy for those who fail to respond to medical therapy. Surgical decompression of the main pancreatic duct by lateral pancreato-jejunostomy is reserved for patients with severe pain non-responsive to other forms of therapy.
Pathogenesis of Pain in Chronic Pancreatitis
Authors: Di Sebastiano Pierluigi , di Mola Fabio F. , Büchler Markus W. , Friess Helmut
Published: March 2005

The pathophysiology of pain in chronic pancreatitis (CP) is incompletely understood. Several hypotheses have been advanced, including pancreatic and extrapancreatic causes. The existence of different hypotheses to explain the genesis of pain in CP also reflects the different therapeutic approaches to pain in these patients. Increased intraductal pressure as a result of single or multiple strictures and/or calculi is believed to be a common cause of pain in CP patients with a dilated main pancreatic duct. Other suggested causes include pancreatic fibrosis, interstitial hypertension and pancreatic ischemia. Additionally, extrapancreatic causes like duodenal and common bile duct stenosis with scarring due to pancreatic inflammation are suggested as factors causing pain in CP. The ‘neurogenic inflammation’ hypothesis is a fascinating theory which is supported by different studies. Immunohistological reports have shown that the amount of neurotransmitters, such as substance P and its receptor, calcitonin gene-related peptide and other neurotransmitters, are increased in afferent pancreatic nerves and a correlation between pain and immune cell infiltration of the nerves has been reported in CP. In this review we will discuss the different pain hypotheses and will present the perspective that neuroimmune interaction is an important factor for pain generation in CP.
Endoscopic Therapy of Chronic Pancreatitis
Authors: Mönkemüller Klaus E. , Kahl Stefan , Malfertheiner Peter
Published: March 2005

We present an overview of endoscopic therapies for chronic pancreatitis (CP) and its associated conditions. It is evident that endoscopy can be a definite therapy for pancreatic pseudocysts, pancreatic ascites and pancreatic duct (PD) disruption. Endoscopic therapy has also been useful in the short-term and medium therapy of common bile duct strictures due to CP, the best results being obtained if there are no calcifications in the head of the pancreas. Although most experts agree that obstruction to the outflow of pancreatic juice and the resulting increased pressure within the main PD is one of the major factors contributing to pain and that endoscopic therapy has been proven effective to remove stones as well as to dilate PD strictures and place stents across the PD, there is no convincing evidence from randomized trials that the patient’s dominant symptom of CP, i.e. pain, is resolved in an appropriate and long-term fashion. We believe that there are other factors which are important in the etiology of chronic pain such as pancreatic inflammation and peripancreatic fibrosis with resulting nerve entrapment around the gland. The reader is reminded that endoscopic therapy is associated with significant and important complications, therefore appropriate patient selection and patient information are of paramount importance. Nevertheless, it is important to consider that one advantage of endoscopic management of CP is that it is less invasive as compared with surgery, often effective for years, does not hinder further surgery, and can be repeated. Finally we want to emphasize that there are many valid surgical, radiological and endoscopic techniques to treat the complications of CP. Therefore, the approach to CP and its complications should be by a multidisciplinary team of gastroenterologists, surgeons, radiologists, endoscopists and pain specialists.
Fluorescence Cystoscopy in the Management of Bladder Cancer: A Help for the Urologist!
Authors: Jichlinski Patrice , Leisinger Hans-Jurg
Published: March 2005

As a disease characterized by a nature polymorphic and fluctuant in its evolution, superficial transitional cell carcinoma of the bladder remains a perpetual therapeutic challenge, and raises a great interest in the development of new diagnostic and surveillance techniques. This paper reviews 10 years of experience of fluorescence cystoscopy, a simple technique perfectly adapted to the current endoscopic equipment. Its principle is to enhance the visual contrast between benign and malignant cells. Three photosensitizing agents are available, two prodrugs: δ-aminolevulinic acid or hexaminolevulinate, and a natural substance: hypericin. With a detection rate of over 90% for carcinoma in situ and a real potential for detecting small tumors overlooked by standard cystoscopy, fluorescence cystoscopy may be clearly recommended in clinical practice. This technique favors a standardization of superficial bladder cancer endoscopic management and is susceptible to have a real impact on the disease recurrence and progression rate.
Follow-Up of Testicular Microlithiasis for Subsequent Testicular Cancer Development
Authors: Pourbagher Mir Ali , Kilinc Ferhat , Guvel Sezgin , Pourbagher Aysin , Egilmez Tulga , Ozkardes Hakan
Published: March 2005

Introduction: To demonstrate the relationship between testicular microlithiasis and testicular tumor development. Patients and Methods: Between January 1996 and March 2004, bilateral testicular microlithiasis was found in 40 of the 5,263 patients who underwent scrotal ultrasonography yielding a prevalence of 0.76%. Of the 40 patients, 4 patients with concomitant testicular tumors were excluded from the study. The remaining 36 patients were enrolled into the study and followed by ultrasonography at 6-month intervals. Results: Patient ages ranged between 1 and 69 years (mean 31 ± 14 years). The median ultrasonography follow-up was 34 months (range, 1–96). Testicular tumor development was not observed in any of these 36 patients during the follow-up period. Conclusions: Extensive evaluation including computerized tomography, testicular tumor markers and testicular biopsyof patients with testicular microlithiasis is unnecessary and also increases patient anxiety. Yet annual ultrasonography and physical examination should be performed if ever until testicular microlithiasis is completely accepted as a nonpremalignant disease.
Outpatient Biofeedback Relaxation of the Pelvic Floor in Treating Pediatric Dysfunctional Voiding: A Short-Course Program Is Effective
Authors: Shei Dei Yang Stephen , Wang Chung Cheng
Published: March 2005

Introduction: We report the treatment results of a short course of biofeedback relaxation of the pelvic floor (BRPF) in treating children with dysfunctional voiding. Materials and Methods: Fourteen girls and 6 boys with videourodynamically proved dysfunctional voiding were enrolled. To increase the awareness of the abnormal voiding pattern, the anatomy of the pelvis and the results of a voiding diary and videourodynamics were extensively explained to the patients/parents. Surface electromyography and uroflowmetry were used as biofeedback tools to teach the adequate relaxation of the pelvic floor during voiding. The child was asked to practice the relaxation technique at home at least twice a day. BRPF was performed once a week until the child had 2 consecutive normal bell-shaped uroflow recordings. Patients were reevaluated at 4, 8, 12 and 24 weeks after BRPF training. Results: The mean patient age was 8.3 ± 3.8 years. The mean number of BRPF training sessions was 2.2 ± 0.9. The mean follow-up period was 18.9 months. Normalization of abnormal uroflowmetry was achieved in 18 patients (90%). The mean maximal uroflow rate and voided volume increased from 13.3 ± 4.3 to 18.0 ± 3.4 ml/s (p < 0.01) and from 138 ± 56 to 193 ± 65 ml (p < 0.01), respectively. The postvoiding residual urine decreased from 54.5 ± 47.6 to 21.3 ± 10.6 ml (p < 0.01). Complete and partial resolution of voiding symptoms was achieved in 14 (70%) and 6 patients (30%), respectively. Recurrence was noted in 2 of the 10 patients who had complete resolution of symptoms and who had been followed up for more than 6 months. Conclusions: Short-course outpatient BRPF is an effective treatment of pediatric dysfunctional voiding.
Translocation of Nuclear Factor-κB on Corneal Epithelial Cells Induced by Ultraviolet B Irradiation
Authors: Lee Do-Hyung , Kim Jung Kweon , Joo Choun-Ki
Published: March 2005

Purpose: This study was performed to elucidate the role of nuclear factor-ĸB (NF-ĸB) in the death of corneal epithelial cells after ultraviolet (UV) irradiation. Methods: Simian virus 40-transfected human corneal epithelial cells (T-HCECs) were used in this study. Cell cultures were irradiated with a UVB (312 nm) source located 10 cm from the bottom of the slides for 10, 20, 30, or 40 s. Cytotoxicity was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Translocation of NF-ĸB was examined by immunocytochemistry using anti-NF-ĸB p65 antibody and electrophoretic mobility shift assay (EMSA). Sulfasalazine and SN-50, specific NF-ĸB inhibitors, were used to confirm the role of NF-ĸB by pretreating samples for 30 min before UV irradiation, after which cytotoxicity and NF-ĸB translocation were evaluated. Results: When T-HCECs were irradiated with UVB, translocation of NF-ĸB was observed with immunocytochemistry. These translocations peaked 2 h after UV irradiation during EMSA. When pretreated with sulfasalazine or SN-50, the translocation of NF-ĸB was blocked. Cellular death after UV irradiation was also markedly blocked by sulfasalazine. Conclusion: These findings suggest that NF-ĸB plays an important role in cellular death after UV irradiation.
Steroid and Vasoactive Treatment for Acute Deafness after Attempted Hearing Preservation Acoustic Neuroma Surgery
Authors: Gouveris Haralampos , Mewes Torsten , Maurer Jan , Mann Wolf
Published: March 2005

Objective: To investigate whether intravenous steroid and vasoactive therapy in the acute postoperative period improves hearing outcome in patients who develop acute deafness after attempted hearing preservation surgery for acoustic neuroma (AN) through a retrosigmoid or a middle cranial fossa approach. Study Design and Setting: Retrospective controlled study in a tertiary care center. Thirty-six patients who had developed acute deafness after hearing preservation surgery for treatment of an AN were reviewed. Preoperative AAOHNS hearing class was A in 2, B in 2 and D in 32 patients. Twenty-seven patients were treated with prednisolone, hydroxyethyl starch 3% and pentoxifylline intravenously for a period of at least 5 days. Nine patients (controls) did not receive any specific steroid or vasoactive therapy. Results: All patients in both groups remained deaf. Conclusions: Intravenous therapy with prednisolone, hydroxyethyl starch 3% and pentoxifylline in the acute postoperative period does not improve hearing in patients who develop acute deafness after attempted hearing preservation surgery for AN.
A New Ossicle Homograft Inactivation/Preservation Procedure: Clinical Results
Authors: Romualdez Joel A. , Stauffer Edouard , Häusler Rudolf , Hotz Michel A.
Published: March 2005

A new NaOH-autoclaving inactivation/preservation procedure (IPP) for ossicle homografts, complying with the actual infectious disease guidelines, has been developed and used in our institution for 5 years. This study compares the clinical and audiological results of middle ear reconstruction using the new NaOH-autoclaving inactivated ossicle homografts (22 patients) and the previously used cialit-formaldehyde inactivation procedure (28 patients). During the follow-up period, no homograft extrusion, resorption or disease transmission was observed either for the NaOH-autoclaving or for the cialit-formaldehyde protocol. A postoperative air-bone gap of less than 20 dB in 44% and a postoperative hearing improvement of 10–50 dB in 70% of patients complies with the published success rates of homograft ossiculoplasty in the literature. The analysis and comparison of both tested IPP-patient groups showed no statistically significant differences in the clinical and the audiological results. The NaOH-autoclaving inactivation/preservation protocol should increase ossicle homograft safety even with respect to prion exposure. The good anatomic and audiological long-term results of the new IPP protocol confirm homograft ossicles as a valid and inexpensive approach for middle ear reconstruction.
CD16+CD57– Natural Killer Cells in Multifocal Motor Neuropathy
Authors: Mizutani K. , Oka N. , Kaji R. , Matsui M. , Asanuma K. , Kubori T. , Kojima Y. , Kanda M. , Kawanishi T. , Tomimoto H. , Akiguchi I. , Shibasaki H.
Published: March 2005

We analyzed the CD16+CD57– lymphocyte subset, which is considered to have strong natural killer (NK) cell activity, in peripheral blood from patients with chronic immune-mediated neuropathies and patients with other neurological diseases. We found that the ratio of CD16+CD57– NK cells to total lymphocytes was increased in 4 of 6 patients with multifocal motor neuropathy (MMN) with persistent conduction block. Since the CD16 molecule is an Fc receptor for immunoglobulin G (IgG), high-dose intravenous immunoglobulin (IVIg) may interfere with CD16+CD57– NK cells via Fc receptor blockade. In addition, cyclophosphamide (Cy) is often used to suppress NK cells. Therefore, our findings may partly account for the effectiveness of IVIg or Cy, which is the current treatment of choice for MMN.
Quantitative Aspects of the Spatial Distribution and Morphological Characteristics of the Sea Bass (Dicentrarchus labrax L.; Teleostei, Serranidae) Trunk Lateral Line Neuromasts
Authors: Faucher Karine , Lagardère Jean-Paul , Aubert Anne
Published: March 2005

The results presented herein report quantitative data relative to the distribution and morphological characteristics of both types of neuromasts encountered on the trunk lateral line of the sea bass (Dicentrarchus labrax, L.). These data were obtained from scanning electron micrographs. They indicate that, as expected, each modified scale of the sea bass possessed a single canal neuromast with long axis oriented parallel to the fish’s long axis. In contrast to several fish species, two thirds of superficial neuromasts observed herein were oriented perpendicular to the fish’s long axis. However, whatever the main orientation of superficial neuromasts, two thirds of their hair bundles were oriented parallel to the long axis of the animal with approximately half of them in the direction of the head. Similar ratios were observed for canal neuromasts whatever the area of the maculae: central or peripheral. For both types of neuromasts it was not possible to clearly distinguish a paired organization of hair bundles with opposing polarities. Superficial neuromasts on each trunk canal scale were located on either the dorsal or ventral side of the canal and appeared to be distributed along the trunk lateral line with a higher probability to be encountered closer to the operculum. The frequency of presence and the average number of superficial neuromasts per scale increased with fish size. We observed a size gradient for canal neuromasts between the operculum and caudal peduncle. This gradation was correlated with a reduction of the width of the central area of the canal segment. Canal neuromasts were always localized in the larger portions of the canal segments. Taken together, these results point out some specific features associated with the sea bass trunk lateral line. With the previous report, they establish the first full description of the trunk lateral line of sea bass and will be useful for upcoming experiments regarding the function of the two types of neuromasts.
Effect of the Macrolide Antibacterial Drug, Tylosin, on TNBS-Induced Colitis in the Rat
Authors: Menozzi Alessandro , Pozzoli Cristina , Poli Enzo , Lazzaretti Mirca , Cantoni Anna , Grandi Daniela , Giovannini Elena , Coruzzi Gabriella
Published: March 2005

Bacterial antigens, such as intestinal microflora, are known to play a role in the pathogenesis of human inflammatory bowel disease (IBD). Tylosin, a macrolide antimicrobial agent, has proven to be effective in cat and dog chronic colitis, but the reasons underlying this efficacy are still unclear. In the present study we evaluated the effects of tylosin on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in the rat, in comparison with the antibacterial drug metronidazole and the corticosteroid budesonide. Colitis was induced by a single intrarectal administration of 10 mg TNBS under light ether anesthesia. Tylosin (20 mg/kg twice a day), metronidazole (160 mg/kg twice a day) and budesonide (500 µg/kg once a day) were given orally for up to 6 days to separate groups of rats. The animals were sacrificed after 6 days and colonic lesions evaluated (colon weight, macroscopic and histologic damage, myeloperoxidase activity). Tylosin and metronidazole significantly lowered macroscopic lesion score, reduced colon weight, the severity of histologic lesions and myeloperoxidase activity; budesonide did not significantly change the parameters of colonic inflammation. These data indicate a protective effect of tylosin against intestinal inflammation, suggesting a major role for bacteria, anaerobes in particular, in the development of TNBS-induced mucosal damage.
A Genome Search for Genetic Determinants That Influence Plasma Fibrinogen Levels
Authors: Soria José Manuel , Almasy Laura , Souto Juan Carlos , Buil Alfonso , Lathrop Mark , Blangero John , Fontcuberta Jordi
Published: March 2005

Background—

Fibrinogen levels are a widely accepted risk factor for cardiovascular disease, but the extent of the genetic component is unknown.

Materials and Results—

To search for these genes, we conducted a genome-wide scan using 21 Spanish families from the Genetic Analysis of Idiopathic Thrombophila (GAIT) Project. Two
loci
were detected: 1 on chromosome 12 and another on chromosome 14. There are no cardiovascular-related candidate genes on chromosome 14, which implies that this
locus
represents a novel cardiovascular risk factor. Importantly, the
locus
on chromosome 12 contains the hepatocyte nuclear factors (TCF1), a candidate gene involved in the hepatocyte-specific transcription of the
fibrinogen α-chain
and β
-chain
genes. Three polymorphisms in
TCF1
showed significant association with fibrinogen levels, supporting the implication of
TCF1
in the determination of this phenotype.

Conclusions—

Two
loci
, 1 on chromosome 12 (most likely the
TCF1
) and another on chromosome 14, are important determinants of fibrinogen levels in Spanish families. These data should help define the relationship between fibrinogen levels and the risk of cardiovascular disease.
Effects of Cholesteryl Ester Transfer Protein Inhibition on High-Density Lipoprotein Subspecies, Apolipoprotein A-I Metabolism, and Fecal Sterol Excretion
Authors: Brousseau Margaret E. , Diffenderfer Margaret R. , Millar John S. , Nartsupha Chorthip , Asztalos Bela F. , Welty Francine K. , Wolfe Megan L. , Rudling Mats , Björkhem Ingemar , Angelin Bo , Mancuso James P. , Digenio Andres G. , Rader Daniel J. , Schaefer Ernst J.
Published: March 2005

Objective—

Pharmacological inhibition of the cholesteryl ester transfer protein (CETP) in humans increases high-density lipoprotein (HDL) cholesterol (HDL-C) levels; however, its effects on apolipoprotein A-I (apoA-I) containing HDL subspecies, apoA-I turnover, and markers of reverse cholesterol transport are unknown. The present study was designed to address these issues.

Methods and Results—

Nineteen subjects, 9 of whom were taking 20 mg of atorvastatin for hypercholesterolemia, received placebo for 4 weeks, followed by the CETP inhibitor torcetrapib (120 mg QD) for 4 weeks. In 6 subjects from the nonatorvastatin cohort, the everyday regimen was followed by a 4-week period of torcetrapib (120 mg BID). At the end of each phase, subjects underwent a primed-constant infusion of (5,5,5-
2
H
3
)-
l
-leucine to determine the kinetics of HDL apoA-I. The lipid data in this study have been reported previously. Relative to placebo, 120 mg daily torcetrapib increased the amount of apoA-I in α1-migrating HDL in the atorvastatin (136%;
P
<0.001) and nonatorvastatin (153%;
P
<0.01) cohorts, whereas an increase of 382% (
P
<0.01) was observed in the 120 mg twice daily group. HDL apoA-I pool size increased by 8±15% in the atorvastatin cohort (
P
=0.16) and by 16±7% (
P
<0.0001) and 34±8% (
P
<0.0001) in the nonatorvastatin 120 mg QD and BID cohorts, respectively. These changes were attributable to reductions in HDL apoA-I fractional catabolic rate (FCR), with torcetrapib reducing HDL apoA-I FCR by 7% (
P
=0.10) in the atorvastatin cohort, by 8% (
P
<0.001) in the nonatorvastatin 120 mg QD cohort, and by 21% (
P
<0.01) in the nonatorvastatin 120 mg BID cohort. Torcetrapib did not affect HDL apoA-I production rate. In addition, torcetrapib did not significantly change serum markers of cholesterol or bile acid synthesis or fecal sterol excretion.

Conclusions—

These data indicate that partial inhibition of CETP via torcetrapib in patients with low HDL-C: (1) normalizes apoA-I levels within α1-migrating HDL, (2) increases plasma concentrations of HDL apoA-I by delaying apoA-I catabolism, and (3) does not significantly influence fecal sterol excretion.
Increased Collagen Deposition and Diastolic Dysfunction but Preserved Myocardial Hypertrophy After Pressure Overload in Mice Lacking PKCε
Authors: Klein Gunnar , Schaefer Arnd , Hilfiker-Kleiner Denise , Oppermann Dagmar , Shukla Praphulla , Quint Anja , Podewski Eva , Hilfiker Andres , Schröder Frank , Leitges Michael , Drexler Helmut
Published: March 2005

Overexpression and activation of protein kinase C-ε (PKCε) results in myocardial hypertrophy. However, these observations do not establish that PKCε is required for the development of myocardial hypertrophy. Thus, we subjected PKCε-knockout (KO) mice to a hypertrophic stimulus by transverse aortic constriction (TAC). KO mice show normal cardiac morphology and function. TAC caused similar cardiac hypertrophy in KO and wild-type (WT) mice. However, KO mice developed more interstitial fibrosis and showed enhanced expression of collagen Iα1 and collagen III after TAC associated with diastolic dysfunction, as assessed by tissue Doppler echocardiography (Ea/Aa after TAC: WT 2.1±0.3 versus KO 1.0±0.2;
P
<0.05). To explore underlying mechanisms, we analyzed the left ventricular (LV) expression pattern of additional PKC isoforms (ie, PKCα, PKCβ, and PKCδ). After TAC, expression and activation of PKCδ protein was increased in KO LVs. Moreover, KO LVs displayed enhanced activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), whereas p42/p44–MAPK activation was attenuated. Under stretch, cultured KO fibroblasts showed a 2-fold increased collagen Iα1 (col Iα1) expression, which was prevented by PKCδ inhibitor rottlerin or by p38 MAPK inhibitor SB 203580. In conclusion, PKCε is not required for the development of a pressure overload–induced myocardial hypertrophy. Lack of PKCε results in upregulation of PKCδ and promotes activation of p38 MAPK and JNK, which appears to compensate for cardiac hypertrophy, but in turn, is associated with increased collagen deposition and impaired diastolic function.
Role of Antioxidant-1 in Extracellular Superoxide Dismutase Function and Expression
Authors: Jeney Viktoria , Itoh Shinichi , Wendt Maria , Gradek Quinton , Ushio-Fukai Masuko , Harrison David G. , Fukai Tohru
Published: March 2005

The extracellular superoxide dismutase (ecSOD or SOD3) is a copper-containing enzyme which is highly expressed in the vasculature. Copper-containing enzymes require copper chaperones for their activity however the chaperone which delivers copper to SOD3 has not previously been defined. Atox1 is a copper chaperone proposed to deliver copper to the trans-Golgi network. Because SOD3 is secreted via the trans-Golgi network, we sought to determine whether Atox1 acts as a copper chaperone for SOD3. Using recombinant human SOD3, we found that the specific activity of SOD3 directly correlates with its copper content (
R
2
=0.99). SOD3 specific activity in the conditioned medium from cultured Atox1
−/−
fibroblasts was markedly decreased, but could be recovered to that of wild-type cells by copper addition. These results indicated that Atox1 is required for delivering copper to SOD3 for its full activity. Unexpectedly, the protein and mRNA levels of SOD3 were dramatically decreased in cultured Atox1
−/−
fibroblasts. This was associated with a marked decrease in SOD3 transcription rate but no change in SOD3 mRNA stability. Overexpression of Atox1 markedly increased SOD3 mRNA in both Atox1
−/−
and Atox1
+/+
cells. These findings indicate that Atox1 positively regulates SOD3 transcription. Because SOD3 protein is upregulated in atherosclerotic vessels, we examined expression of Atox1 in vessels from ApoE
−/−
mice. Western and immunohistochemical analysis in ApoE
−/−
mice revealed that both Atox1 and SOD3 protein levels are markedly increased in atherosclerotic intimal lesions. In summary, Atox1 functions not only as a copper chaperone for SOD3 but also as a positive regulator for SOD3 transcription and may have an important role in modulating oxidative stress in the cardiovascular system.
Adenoviral Gene Transfer of FGF-5 to Hibernating Myocardium Improves Function and Stimulates Myocytes to Hypertrophy and Reenter the Cell Cycle
Authors: Suzuki Gen , Lee Te-Chung , Fallavollita James A. , Canty John M.
Published: March 2005

Fibroblast growth factors (FGFs) have diverse actions on the myocardium but the importance of stimulating angiogenesis versus direct effects of FGFs on cardiac myocytes is unclear. We used intracoronary injection of a replication-deficient adenoviral construct overexpressing FGF-5 (AdvFGF-5) to improve flow and function in swine with hibernating myocardium. Two-weeks after AdvFGF-5 (n=8), wall-thickening increased from 2.4±0.04 to 4.7±0.7 mm in hibernating LAD regions (
P
<0.05) whereas remote wall-thickening was unchanged (6.7±0.4 to 5.8±0.5 mm). This was associated with small increases in resting flow to dysfunctional myocardium, but flow during adenosine was unchanged (LAD 1.45±0.27 versus 1.46±0.23 mL/min per g and remote 4.84±0.23 versus 4.71±0.47 mL/min per g,
P
=NS). Unexpectedly, animals receiving AdvFGF-5 demonstrated a 29% increase in LV mass over the 2-week period (
P
<0.05 versus untreated animals with hibernating myocardium and normal shams). Histological analysis confirmed profound myocyte cellular hypertrophy in AdvFGF-5 treated myocardium (19.9±0.32 versus 15.2±0.92 μm in untreated,
P
<0.001). Myocytes in the proliferative phase of the cell cycle (Ki-67 staining) increased 7-fold after AdvFGF-5 (2,904±405 versus 409±233 per 10
6
myocyte nuclei in untreated,
P
<0.05). Myocyte nuclei in the mitotic phase (phosphorylated histone H3 staining) also increased after AdvFGF-5 (127±24 versus 35±13 per 10
6
myocyte nuclei in untreated,
P
<0.05). Thus, rather than angiogenesis, stimulation of hypertrophy and reentry of a small number of myocytes into the mitotic phase of the cell cycle are responsible for the effects of AdvFGF-5 on function. Although additional mechanisms may contribute to the improvement in wall-thickening, overexpression of AdvFGF-5 may afford a way to restore function in hibernating myocardium and ameliorate heart failure in chronic ischemic cardiomyopathy.
A Pilot Study of Normobaric Oxygen Therapy in Acute Ischemic Stroke
Authors: Singhal Aneesh B. , Benner Thomas , Roccatagliata Luca , Koroshetz Walter J. , Schaefer Pamela W. , Lo Eng H. , Buonanno Ferdinando S. , Gonzalez R. Gilberto , Sorensen A. Gregory
Published: March 2005

Background and Purpose—

Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke.

Methods—

We randomized patients with acute stroke (<12 hours) and perfusion-diffusion “mismatch” on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours (n=9) or room air (controls, n=7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups.

Results—

Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (±SD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8±22% versus 149.1±41%;
P
=0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline “ischemic” to 4-hour “non-ischemic” values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These “during-therapy” benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls (
P
=0.6).

Conclusions—

High-flow oxygen therapy is associated with a transient improvement of clinical deficits and MRI abnormalities in select patients with acute ischemic stroke. Further studies are warranted to investigate the safety and efficacy of hyperoxia as a stroke therapy.
The Use of Subsets of Test Questions in an Angoff Standard-Setting Method
Authors: Ferdous Abdullah A. , Plake Barbara S.
Published: March 2005

In an Angoff standard-setting procedure, judges estimate the probability that a hypothetical randomly selected minimally competent candidate will answer correctly each item constituting the test. In many cases, these item performance estimates are made twice, with information shared with the judges between estimates. Especially for long tests, this estimation process can be time consuming and fatiguing for the participants. This study addressed the possibilities of reducing the number of items individual judges consider in an Angoff standard-setting study. The results of this study suggest that 50% of test items may be sufficient to estimate an equivalent passing score in an Angoff setting study. This could result in substantial savings of time and resources not only for the agencies that have been carrying out this activity but also for the practitioners (judges) who participate in standard-setting studies.
Physical Self-Concept in Adolescence: Generalizability of a Multidimensional, Hierarchical Model Across Gender and Grade
Authors: Hagger Martin S. , Biddle Stuart J. H. , John Wang C. K.
Published: March 2005

This study tests the generalizability of the factor pattern, structural parameters, and latent mean structure of a multidimensional, hierarchical model of physical self-concept in adolescents across gender and grade. A children's version of the Physical Self-Perception Profile (C-PSPP) was administered to seventh-, eighth- and ninth-grade high school students ( N= 2,969). Two a priori models were proposed: a confirmatory factor-analytic model that hypothesized a multidimensional model of physical self-concept; and a structural equation model that proposed a multidimensional, hierarchical structure with global self-concept as a superordinate construct and physical self-concept as a domainlevel construct that explained the covariances among the subdomains of the C-PSPP. Both models satisfied multiple criteria for goodness-of-fit with the data in each individual gender and grade sample. Tests of the invariance of the factor pattern and structural parameters for both models across gender and grade were supported. Consistent with findings from other contexts, latent means analysis suggests that physical self-concept scores was higher in boys.
Women and children in the global sex trade
Authors: Roby Jini L.
Published: March 2005

English

Around 1.2 million women and girls enter the sex trade every year, generating US$1.5 billion annually for their exploiters. Between 30 percent and 35 percent of the victims are girls under 18 years old. This article explores the growing problem of global trafficking of women and children for prostitution and outlines specific policy recommendations.

French

Environ 1,2 millions de femmes et de filles entrent le commerce de sexe chaque année, produisant $1,5 milliards dollars américains annuellement pour leurs exploiteurs. Les filles en bas de 18 ans comptent pour 30-35’ pour cent des victimes. Cet article explore le problème croissant du trafic global des femmes et des enfants, et offre des recommandations spécifiques pour les politiques sociales.

Spanish

Cada año 1,2 millones de mujeres y niñas entran en la industria del sexo, beneficiando a sus explotadores con $1,5 billones anuals. Del 30 al 35 por ciento de las víctimas son menores de 18 años. En este artículo se explora el problema creciente de prostitución de mujeres y menores de edad, y se perfilan algunas recomandaciones específicas de política social.
The Meanings of Home in Postwar Britain
Authors: Langhamer Claire
Published: March 2005

This article explores the meanings of ‘home’ in postwar Britain: how was home situated in public discourse and what was the relationship between public perception, individual desire and material reality? It considers the extent to which the British home was re-made in these years asking whether domesticity 1950s-style was distinct from previous models and exploring the degree of penetration achieved by a home-centred model. The article draws upon life history sources and social survey materials that allow access to subjective understandings of ‘home’. In particular, it employs evidence collected by the pioneering British social investigative organization, Mass-Observation, to explore both historically-sited meanings of home and recently-solicited memories of the postwar period.
The Effects of Urban Patterns on Ecosystem Function
Authors: Alberti Marina
Published: March 2005

Urban ecological systems are characterized by complex interactions among social, economic, institutional, and environmental variables. These interactions generate complex human-dominated landscapes, which significantly influence the functioning of local and global earth ecosystems and the services they provide to humans and other life on earth. Urban development fragments, isolates, and degrades natural habitats; simplifies and homogenizes species composition; disrupts hydrological systems; and modifies energy flow and nutrient cycling. Urban areas also appropriate a large share of earth’s carrying capacity from other regions in terms of resource input and waste sinks. Change in ecological conditions that result from human actions in urban areas ultimately affect human health and well-being. In this article, the author reviews the empirical evidence on the effects that patterns of urban development have on ecosystem function. Urban development affects the spatial heterogeneity of the landscape (i.e., pattern of variation in land cover) and spread of disturbance (i.e., invasive species). The author proposes that alternative urban patterns generate differential ecological effects. The review reveals that the interactions between urban development patterns and ecosystem dynamics are still poorly understood. The author draws on an empirical study of the Puget Sound metropolitan region currently developed at the University of Washington to propose directions for future empirical research that can inform strategies to minimize urban impacts on ecosystems.