bluuebunny/crossref_metadata_2025 huggingface dataset:
M-GROUPS OF ORDER paqb: A THEOREM OF LOUKAKI
Authors: LEWIS MARK L.
Published: August 2006

Let p and q be odd primes, and let G be an M-group of order paqb. Loukaki has proven that if N is a normal subgroup of G, then N is an M-group. In this paper, we present a simpler proof of Loukaki's theorem. We also present a slight generalization of Loukaki's theorem.
A CLASS OF ONE-DIMENSIONAL MDS CONVOLUTIONAL CODES
Authors: GLUESING-LUERSSEN HEIDE , LANGFELD BARBARA
Published: August 2006

A class of one-dimensional convolutional codes will be presented. They are all MDS codes, i.e. have the largest distance among all one-dimensional codes of the same length n and overall constraint length δ. Furthermore, their extended row distances are computed, and they increase with slope at least n - δ. In certain cases of the algebraic parameters, we will also derive parity check matrices of Vandermonde type for these codes. Finally, cyclicity in the convolutional sense of [8] will be discussed for our class of codes. It will turn out that they are cyclic if and only if the field element used in the generator matrix has order n. This can be regarded as a generalization of the block code case.
THE MALCEV POISSON SUPERALGEBRA OF THE FREE MALCEV SUPERALGEBRA ON ONE ODD GENERATOR
Authors: SHESTAKOV IVAN , ZHUKAVETS NATALIA
Published: August 2006

A base of the Malcev Poisson superalgebra related with the free Malcev superalgebra on one odd generator is constructed. As a corollary, a pre-base, that is, a set of elements that spans the free alternative superalgebra on one odd generator is obtained.
Yellow Fever: A Disease that Has Yet to be Conquered
Authors: Barrett Alan D.T. , Higgs Stephen
Published: August 2006

Yellow fever virus (YFV) is the prototype member of the genus Flavivirus, a group of viruses that are transmitted between vertebrates by arthropod vectors. The virus is found in tropical regions of Africa and South America and is transmitted to primates by mosquitoes: Aedes spp. in Africa and Haemagogus and Sabethes spp. in South America. Despite the availability of an effective vaccine, yellow fever (YF) is considered a reemerging disease owing to its increased incidence in the past 25 years. Molecular epidemiologic data suggest there are seven genotypes of YFV that are geographically separated, and outbreaks of disease are more associated with particular genotypes. In addition, the risk of urban YF, owing to transmission of the virus by Aedes aegypti, is increasing in Africa, as is the potential of urban YF returning to South America. Both present serious potential public health problems to large population centers.
Temporal Measures and Neural Strategies for Detection of Tones in Noise Based on Responses in Anteroventral Cochlear Nucleus
Authors: Gai Yan , Carney Laurel H.
Published: August 2006

To examine possible neural strategies for the detection of tones in broadband noise, single-neuron extracellular recordings were obtained from the anteroventral cochlear nucleus (AVCN) in anesthetized gerbils. Detection thresholds determined by average discharge rate and several temporal metrics were compared with previously reported psychophysical detection thresholds in cats ( Costalupes 1985 ). Because of their limited dynamic range, the average discharge rates of single neurons failed to predict psychophysical detection thresholds for relatively high-level noise at all measured characteristic frequencies (CFs). However, temporal responses changed significantly when a tone was added to a noise, even for neurons with flat masked rate-level functions. Three specific temporal analyses were applied to neural responses to tones in noise. First, temporal reliability, a measure of discharge time consistency across stimulus repetitions, decreased with increasing tone level for most AVCN neurons at all measured CFs. Second, synchronization to the tone frequency, a measure of phase-locking to the tone, increased with tone level for low-CF neurons. Third, rapid fluctuations in the poststimulus time histograms (PSTHs) decreased with tone level for a number of neurons at all CFs. For each of the three temporal measures, some neurons had detection thresholds at or below psychophysical thresholds. A physiological model of a higher-stage auditory neuron that received simple excitatory and inhibitory inputs from AVCN neurons was able to extract the PSTH fluctuation information in a form of decreased rate with tone level.
Multiple Types of GABAA Receptors Mediate Inhibition in Brain Stem Parasympathetic Cardiac Neurons In the Nucleus Ambiguus
Authors: Bouairi Euguenia , Kamendi Harriet , Wang Xin , Gorini Christopher , Mendelowitz David
Published: August 2006

Recent work suggests neurons can have different types of γ-aminobutyric acid type A (GABAA) receptors that mediate phasic inhibitory postsynaptic currents (IPSCs) and tonic currents. This study examines the diversity of GABAergic synaptic currents in parasympathetic cardioinhibitory neurons that receive rhythmic bursts of GABAergic neurotransmission. Focal application of gabazine (25 μM) to cardiac vagal neurons in vitro did not change the frequency of firing in spontaneously active neurons or the resting membrane potential; however, picrotoxin (100 μM) significantly depolarized cardiac vagal neurons and increased their firing. Similarly, gabazine (25 μM) selectively blocked GABAergic IPSCs but did not change holding current in cardiac vagal neurons, whereas picrotoxin (100 μM) not only blocked GABAergic IPSCs but also rapidly decreased the tonic current. Because the tonic current could be attributable to activation of GABA receptors by ambient GABA or, alternatively, spontaneous opening of constitutively active GABA channels, an antagonist for the GAT-1 GABA transporter NO-711 (10 μM) was applied to distinguish between these possibilities. NO-711 did not significantly alter the holding current in these neurons. The benzodiazepine flunitrazepam (1 μM) significantly increased the tonic current and GABAergic IPSC decay time; surprisingly, however, in the presence of gabazine flunitrazepam failed to elicit any change. These results suggest cardiac vagal neurons possess gabazine-sensitive GABAA receptors that mediate phasic synaptic currents, a gabazine-insensitive but picrotoxin-sensitive extrasynaptic tonic current that when blocked depolarizes and increases the firing rate of cardiac vagal neurons, and benzodiazepines recruit a third type of GABAA receptor that is sensitive to gabazine and augments the extrasynaptic tonic current.
CHEK2-Positive Breast Cancers in Young Polish Women
Authors: Cybulski Cezary , Górski Bohdan , Huzarski Tomasz , Byrski Tomasz , Gronwald Jacek , Dębniak Tadeusz , Wokołorczyk Dominika , Jakubowska Anna , Kowalska Elżbieta , Oszurek Oleg , Narod Steven A. , Lubiński Jan
Published: August 2006

Purpose: To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers.

Experimental Design: We studied 3,228 women diagnosed with breast cancer under the age of 51 years and 5,496 population controls. CHEK2 mutations were detected by RFLP-PCR or allele-specific oligonucleotide-PCR assays. Clinical and pathologic features of CHEK2-positive cases and CHEK2-negative cases were compared.

Results: A truncating CHEK2 mutation (1100delC or IVS2+1G>A) was seen in 47 of 3,228 cases and in 34 of 5,496 controls (odds ratio, 2.4; P = 0.0001). The CHEK2 I157T missense mutation was present in 207 of 3,228 cases, compared with 264 of 5,496 controls (odds ratio, 1.4; P = 0.002). Breast cancers in women with a CHEK2 mutation were more commonly of lobular histology (21.5% versus 15.8%; P = 0.05), of size >2 cm (54.8% versus 43.5%; P = 0.01), or of multicentric origin (28.7% versus 19.5%; P = 0.01) than were cancers from women without a CHEK2 mutation. Bilateral cancers were equally common in both subgroups.

Conclusion: Three founder alleles in CHEK2 contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of CHEK2 mutations seem to be similar to those of breast cancers in the population at large.
Preoperative Serum Caveolin-1 as a Prognostic Marker for Recurrence in a Radical Prostatectomy Cohort
Authors: Tahir Salahaldin A. , Frolov Anna , Hayes Teresa G. , Mims Martha P. , Miles Brian J. , Lerner Seth P. , Wheeler Thomas M. , Ayala Gustavo , Thompson Timothy C. , Kadmon Dov
Published: August 2006

Purpose: Up-regulation of caveolin-1 (cav-1) is associated with virulent prostate cancer, and serum cav-1 levels are elevated in prostate cancer patients but not in benign prostatic hyperplasia. In this study, we evaluated the potential of high preoperative serum cav-1 levels to predict biochemical progression of prostate cancer. The value of the combined preoperative markers, prostate-specific antigen (PSA), biopsy Gleason score, and serum cav-1 for predicting biochemical recurrence was also investigated.

Experimental Design: Serum samples taken from 419 prostate cancer patients before radical prostatectomy were selected from our Specialized Programs of Research Excellence prostate cancer serum and tissue bank. Serum samples were obtained 0 to 180 days before surgery and all patients had complete data on age, sex, race, stage at enrollment, and follow-up for biochemical recurrence. Serum cav-1 levels were measured according to our previously reported ELISA protocol.

Results: Cav-1 levels were measured in the sera of 419 prostate cancer patients; the mean serum level was 4.52 ng/mL (median 1.01 ng/mL). Patients with high serum cav-1 levels had a 2.7-fold (P = 0.0493) greater risk of developing biochemical recurrence compared with those with low serum cav-1 levels. Importantly, patients with serum PSA ≥ 10 ng/mL and elevated levels of serum cav-1 had 2.44 times higher risk (P = 0.0256) of developing biochemical recurrence compared with patients with low levels of cav-1. In addition, high serum cav-1 levels combined with increasing biopsy Gleason score predicted much shorter recurrence-free survival in the group of patients with PSA ≥ 10 ng/mL (P = 0.0353). Cav-1 was also able to distinguish between high- and low- risk patients with biopsy Gleason score of seven, after adjusting, for patients PSA levels (P = 0.0429).

Conclusions: Overall, elevated preoperative levels of serum cav-1 predict decreased time to cancer recurrence. In the subset of patients with serum PSA of ≥10 ng/mL, the combination of serum cav-1 and biopsy Gleason score has the capacity to predict time to biochemical recurrence.
Antitumor Effect of Trastuzumab for Pancreatic Cancer with High HER-2 Expression and Enhancement of Effect by Combined Therapy with Gemcitabine
Authors: Kimura Kenjiro , Sawada Tetsuji , Komatsu Midori , Inoue Masafumi , Muguruma Kazuya , Nishihara Tamahiro , Yamashita Yoshito , Yamada Nobuya , Ohira Masaichi , Hirakawa Kosei
Published: August 2006

Purpose: The purpose of the present study was to evaluate whether trastuzumab has antitumor effect against pancreatic cancer and whether this effect is concordant with levels of HER-2, which is reportedly overexpressed in pancreatic cancer. We also investigated whether the effect is potentiated in combined therapy with gemcitabine.

Experimental Design: Using immunohistochemistry and FACScan, we analyzed HER-2 expression in 16 pancreatic cancer cell lines. The in vitro antiproliferative effect of trastuzumab, alone and in combination with gemcitabine, was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The in vitro antibody-dependent cell-mediated cytotoxicity of trastuzumab was investigated by 51Cr release assay. The in vivo antitumor effect of trastuzumab, alone and in combination with gemcitabine, was evaluated in nude mouse xenograft growth. The survival benefit was evaluated in a Capan-1 orthotopic implanted nude mouse model.

Results: HER-2 expression of 2+ or more was observed in 10 and of 3+ in 2 of the 16 cell lines. No in vitro growth-inhibitory effect of trastuzumab was found in any cell line, but trastuzumab induced antibody-dependent cell-mediated cytotoxicity in proportion to HER-2 expression level. Trastuzumab inhibited tumor growth in Capan-1 (HER-2: 3+) xenografts and prolonged survival in the orthotopic model. These effects were increased by combined therapy with gemcitabine. In contrast, trastuzumab exhibited no antitumor effect against PANC-1 (HER-2: 1+) or SW1990 (HER-2: 2+) xenografts.

Conclusions: The antitumor effect of trastuzumab in pancreatic cancer with high HER-2 expression was shown in vitro and in vivo. Clinical application of trastuzumab is expected in pancreatic cancer with 3+ HER-2 expression.
Phase I/II Study of Imatinib Mesylate for Recurrent Malignant Gliomas: North American Brain Tumor Consortium Study 99-08
Authors: Wen Patrick Y. , Yung W.K. Alfred , Lamborn Kathleen R. , Dahia Patricia L. , Wang Yanfeng , Peng Bin , Abrey Lauren E. , Raizer Jeffrey , Cloughesy Timothy F. , Fink Karen , Gilbert Mark , Chang Susan , Junck Larry , Schiff David , Lieberman Frank , Fine Howard A. , Mehta Minesh , Robins H. Ian , DeAngelis Lisa M. , Groves Morris D. , Puduvalli Vinay K. , Levin Victor , Conrad Charles , Maher Elizabeth A. , Aldape Kenneth , Hayes Michael , Letvak Laurie , Egorin Merrill J. , Capdeville Renaud , Kaplan Richard , Murgo Anthony J. , Stiles Charles , Prados Michael D.
Published: August 2006

Purpose: Phase I: To determine the maximum tolerated doses, toxicities, and pharmacokinetics of imatinib mesylate (Gleevec) in patients with malignant gliomas taking enzyme-inducing antiepileptic drugs (EIAED) or not taking EIAED. Phase II: To determine the therapeutic efficacy of imatinib.

Experimental Design: Phase I component used an interpatient dose escalation scheme. End points of the phase II component were 6-month progression-free survival and response.

Results: Fifty patients enrolled in the phase I component (27 EIAED and 23 non-EIAED). The maximum tolerated dose for non-EIAED patients was 800 mg/d. Dose-limiting toxicities were neutropenia, rash, and elevated alanine aminotransferase. EIAED patients received up to 1,200 mg/d imatinib without developing dose-limiting toxicity. Plasma exposure of imatinib was reduced by ∼68% in EIAED patients compared with non-EIAED patients. Fifty-five non-EIAED patients (34 glioblastoma multiforme and 21 anaplastic glioma) enrolled in the phase II component. Patients initially received 800 mg/d imatinib; 15 anaplastic glioma patients received 600 mg/d after hemorrhages were observed. There were 2 partial response and 6 stable disease among glioblastoma multiforme patients and 0 partial response and 5 stable disease among anaplastic glioma patients. Six-month progression-free survival was 3% for glioblastoma multiforme and 10% for anaplastic glioma patients. Five phase II patients developed intratumoral hemorrhages.

Conclusions: Single-agent imatinib has minimal activity in malignant gliomas. CYP3A4 inducers, such as EIAEDs, substantially decreased plasma exposure of imatinib and should be avoided in patients receiving imatinib for chronic myelogenous leukemia and gastrointestinal stromal tumors. The evaluation of the activity of combination regimens incorporating imatinib is under way in phase II trials.
Improving Antitumor Immune Responses by Circumventing Immunoregulatory Cells and Mechanisms
Authors: Lizée Gregory , Radvanyi Laszlo G. , Overwijk Willem W. , Hwu Patrick
Published: August 2006

Although numerous immunotherapeutic strategies have been studied in patients with cancer, consistent induction of clinical responses remains a formidable challenge. Cancer vaccines are often successful at generating elevated numbers of tumor-specific T lymphocytes in peripheral blood, however, despite this, tumors usually continue to grow unabated. Recent evidence suggests that endogenous regulatory cells, known to play a major role in the induction of immune tolerance to self and prevention of autoimmunity, as well as suppressive myeloid cells invoked in the tumor-bearing state, may be largely responsible for preventing effective antitumor immune responses. This review will focus on the major regulatory cell subtypes, including CD4+CD25+ T-regulatory cells, type 1 regulatory T cells, natural killer T cells, and immature myeloid cells. Studies in humans and in animal models have shown a role for all of these cells in tumor progression, although the mechanisms by which they act to suppress immunity remain largely undefined. Elucidation of the dominant molecular mechanisms mediating immune suppression in vivo will allow more precise targeting of the relevant regulatory cell populations, as well as the development of novel strategies and clinical reagents that will directly block molecules that induce the suppression of antitumor immunity.
CHIR-258 Is Efficacious in A Newly Developed Fibroblast Growth Factor Receptor 3–Expressing Orthotopic Multiple Myeloma Model in Mice
Authors: Xin Xiaohua , Abrams Tinya J. , Hollenbach Paul W. , Rendahl Katherine G. , Tang Yan , Oei Yoko A. , Embry Millicent G. , Swinarski Debbie E. , Garrett Evelyn N. , Pryer Nancy K. , Trudel Suzanne , Jallal Bahija , Mendel Dirk B. , Heise Carla C.
Published: August 2006

Purpose: The ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) results from a t(4;14) chromosomal translocation that occurs in ∼15% of multiple myeloma (MM) patients and confers a particularly poor prognosis. This study assesses the antimyeloma activity of CHIR-258, a small-molecule inhibitor of multiple receptor tyrosine kinases that is currently in phase I trials, in a newly developed FGFR3-driven preclinical MM animal model.

Experimental Design: We developed an orthotopic MM model in mice using a luciferase-expressing human KMS-11-luc line that expresses mutant FGFR3 (Y373C). The antimyeloma activity of CHIR-258 was evaluated at doses that inhibited FGFR3 signaling in vivo in this FGFR3-driven animal model.

Results: Noninvasive bioluminescence imaging detected MM lesions in nearly all mice injected with KMS-11-luc cells, which were mainly localized in the spine, skull, and pelvis, resulting in frequent development of paralysis. Daily oral administration of CHIR-258 at doses that inhibited FGFR3 signaling in KMS-11-luc tumors in vivo resulted in a significant inhibition of KMS-11-luc tumor growth, which translated into a significant improvement in animal survival.

Conclusions: Our data provide a relevant preclinical basis for clinical trials of CHIR-258 in FGFR3-positive MM patients.
Association between the Epstein-Barr Virus and Hodgkin’s Lymphoma in the North-Eastern Part of Hungary: Effects on Therapy and Survival
Authors: Keresztes Katalin , Miltenyi Zsofia , Bessenyei Beata , Beck Zoltan , Szollosi Zoltan , Nemes Zoltan , Olah Eva , Illes Arpad
Published: August 2006

This retrospective study included 109 patients with Hodgkin’s lymphoma (HL; 45 females, 64 males). In 47 of the 109 HL patients (43%), immunohistochemical analysis of their formalin-fixed, paraffin-embedded histologic samples revealed Epstein-Barr virus (EBV) by latent membrane protein (LMP) 1. The highest virus association (50%) was found with the mixed cellularity histologic subtype, especially in patients aged 11–20 and >50 years. Virus positivity in nodular sclerosis was 35% (negative cases accumulated in patients aged 15–30 years). Regarding clinical stages, histologic subtypes, general symptoms, treatments employed and response to treatment, the EBV-positive group was not significantly different from the virus-negative group. During the mean follow-up time of 83 months (9–300 months), the overall or event-free survival of EBV-negative patients was more favorable than that of EBV-positive patients, although the difference was not significant (p = 0.16 and p = 0.24, respectively). EBV infection may be involved in the pathogenesis of HL in our Hungarian study cohort, but it does not significantly affect clinical symptoms, therapeutic results or complete and event-free survival of HL patients.
Hemophagocytic Syndrome in Kidney Transplant Recipients: Report of Four Cases from a Single Center
Authors: Gurkan Alihan , Yakupoglu Ulkem , Yavuz Asuman , Dikici Hilmi , Yakupoglu Yarkin Kamil , Tuncer Murat , Demirbas Alper , Ersoy Fevzi
Published: August 2006

Background: The prognosis of hemophagocytic syndrome (HPS) in kidney transplant recipients is reported to be poor, however the optimal therapeutic approach is still unclear. Patients and Methods: The clinical and follow-up data of the 4 patients with HPS (3 male, 1 female; age 39.7 ± 11.3 years) among 368 kidney transplant recipients during a 5-year period were retrospectively analyzed. Results: HPS developed 35–61 days in the post-transplant period. All 4 patients presented with fever. Hepatosplenomegaly and lymphadenopathy were observed only in the first patient. Laboratory tests revealed pancytopenia and hyperferritinemia in all patients, but elevated liver enzymes were observed in 3. Two patients had cytomegalovirus infection, and 1 had Epstein-Barr virus infection. Three patients died despite aggressive supportive therapy, however the fourth case survived after graft nephrectomy. Conclusion: HPS pathogenesis in kidney transplants appears to be related with the graft itself. Graft nephrectomy may be the preferable therapeutic approach for kidney transplant recipients with HPS resistant to standard supportive therapy.
Clonal Karyotype Evolution Involving Ring Chromosome 1 with Myelodysplastic Syndrome Subtype RAEB-t Progressing into Acute Leukemia
Authors: Duell Thomas , Poleck-Dehlin Brigitte , Schmid Christoph , Wunderlich Bettina , Ledderose Georg , Mittermüller Johann , Kolb Hans Jochen , Schmetzer Helga
Published: August 2006

Karyotypic evolution is a well-known phenomenon in patients with malignant hematological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hematological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes [46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome [46,XY,r(1),+8,–21/45,XY,r(1),+8,–21,–22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient’s HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient’s clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor’s PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hematological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease.
High Frequency of Postcoital Penis Cleaning in Budongo Chimpanzees
Authors: O’Hara Sean J. , Lee Phyllis C.
Published: August 2006

Cultural or tool use behaviours are typically conducted in social or food procurement contexts where the individual interacts with conspecifics, heterospecifics or environmental features. We report on postcoital penis cleaning in chimpanzees, an activity that does not fit this pattern. In penis cleaning, leaves are employed as ‘napkins’ to wipe clean the penis after sex. Alternatively, the same cleaning motion can be done without leaves, simply using the fingers. Not all chimpanzee communities studied across Africa clean their penes and, where documented, the behaviour is rare. By contrast, we identify postcoital penis cleaning in Budongo Forest, Uganda, as customary and corroborate penis cleaning as another cultural trait in chimpanzees, one that is specific to only a subset of the eastern subspecies of chimpanzee(Pan troglodytes schweinfurthii).
Sanje Mangabey Cercocebus sanjei Kills an African Crowned Eagle Stephanoaetus coronatus
Authors: Jones Trevor , Laurent Sebastian , Mselewa Firidolin , Mtui Abel
Published: August 2006

We present the first ever reported observations of a hunting African crowned eagle Stephanoaetus coronatus being killed by a primate, in the Udzungwa Mountains of south-central Tanzania. An adult female eagle launched an attack on a young Sanje mangabey Cercocebus sanjei who was feeding in a tree, but was intercepted and bitten by an adult mangabey who was feeding nearby. The adult mangabey and the eagle then fell together 25 m to the forest floor below. The eagle subsequently died from her injuries, while the mangabey escaped and is thought to have survived. This rare event is briefly discussed in the context of previous accounts of primate-crowned eagle interactions.
Early and Rapid Prenatal Diagnosis of Monosomy 2q36.1 in Trophoblast Cells
Authors: Tachdjian Gérard , Aboura Azzedine , Brisset Sophie , Dommergues Marc , Gajdos Vincent , Labrune Philippe
Published: August 2006

Objectives: CVS is the earliest procedure for cytogenetic analysis but the quality of metaphases obtained does not allow the characterization of subtle chromosomal anomalies. We report the application interphase fluorescence in situ hybridization for the rapid prenatal diagnosis of a subtle structural chromosome anomaly in trophoblast cells. Methods and Results: The foetus was karyotyped because of a paternal complex chromosomal anomaly 46,XY,inv(2)(q14.3q35),ins(10;2)(q25;q36.1q36.1). Fluorescence in situ hybridization analyses were performed on interphase nuclei and metaphase chromosomes from uncultured chorionic villi using bacterial artificial chromosomes specific for the 2q chromosomal region. Direct conventional cytogenetics showed an apparently normal male karyotype, whereas fluorescence in situ hybridization analysis showed a deletion of the chromosomal region 2q36.1 and a paracentric inversion of the chromosome 2q leading to a partial monosomy 2q36.1. Conclusion: This strategy allowed us to offer an early and rapid chromosomal analysis for this couple leading to a better management of the pregnancy. This report demonstrates that interphase fluorescence in situ hybridization can be used in direct CVS for a rapid and early prenatal diagnosis of complex chromosomal rearrangements.
First Trimester Ultrasound Diagnosis of Lethal Multiple Pterygium Syndrome
Authors: Gundogan Munire , Fong Katherine , Keating Sarah , Pierre-Louis Jacqueline , Chitayat David
Published: August 2006

Objective: Diagnosis of lethal multiple pterygium syndrome in the first trimester of pregnancy. Methods: A 38-year-old woman attended our ultrasound (US) clinic at 11.2 weeks gestation. She has had two previous stillbirths affected by lethal multiple pterygium syndrome. Transabdominal and transvaginal US were performed and identified a recurrence. Autopsy findings are compared to the fetal US findings. Results: Fetal US showed a markedly increased nuchal translucency, fixed flexion deformities of the elbows and knees bilaterally, cutaneous webs across both elbow joints and absent fetal movements. The patient decided to terminate the pregnancy and a D&C was performed. Pathology of intact fetal parts showed flexion deformity of the right elbow with a cutaneous web, and ulnar deviation of the right wrist. Conclusion: Increased nuchal translucency, absent limb movements, multiple joint contractures and cutaneous webs on US allowed the diagnosis of lethal multiple pterygium syndromes in the first trimester of pregnancy.
Laser Ablation of Foetal Microcystic Lung Lesion: Successful Outcome and Rationale for Its Use
Authors: Ong S.S.C. , Chan S.Y. , Ewer A.K. , Jones M. , Young P. , Kilby M.D.
Published: August 2006

Objective: A foetus with an echodense, microcystic lung lesion complicated by non-immune hydrops has a high mortality rate. Because of the limited treatment options available, laser ablation was offered in an attempt to reduce the size of the lesion and reduce hydrops fetalis. Methods and Results: A 25-year-old nulliparous woman presented at 21 weeks gestation. Ultrasound revealed a male foetus with a large microcystic right sided lung lesion that completely occupied the right hemithorax causing marked mediastinal deviation. The foetus was hydropic with polyhydramnios. Percutaneous laser ablation of the large microcystic lung lesion was performed under direct ultrasound control. At a power setting of 45 W, and using a 400 µm Nd:YAG laser fibre, the core of the lesion was photocoagulated in pulses lasting 5 s at 5 s intervals. The total target dose was 1683 J. This led to a marked but temporary reduction in amniotic fluid volume. The patient was commenced on sulindac and amniodrainage was performed at 27 weeks as reaccumulation of the polyhydramnios occurred. Pre-eclampsia complicated the pregnancy at 38 weeks gestation and an emergency caesarean section was performed. The baby underwent a thoracotomy and lobectomy at 48 h of age, made a good recovery, and is currently well 8 weeks post-delivery. Conclusions: In cases of cystic lung lesion complicated by hydrops, laser ablation should be considered as a treatment option.
Differences in Serum GH Cut-Off Values for Pharmacological Tests of GH Secretion Depend on the Serum GH Method
Authors: Chaler E.A. , Rivarola M.A. , Guerci B. , Ciaccio M. , Costanzo M. , Travaglino P. , Maceiras M. , Pagani S. , Meazza C. , Bozzola E. , Barberi S. , Bozzola M. , Belgorosky A.
Published: August 2006

Background: The serum GH cut-off value for pharmacological tests of GH secretion (PhT GH) depends on the type of test and also on the method used for determining serum GH. Cut-off serum GH values as different as 5–10 ng/ml, have been reported, and have been validated biochemically. We have used the growth velocity (GV)-standard deviation score (SDS) during the first year of treatment with rhGH to validate these cut-offs on a biological basis. Methods: Fifty pre-pubertal patients with short stature (height ≤–2 SDS and GV ≤–1.2 SDS) were studied. GH deficiency (GHD) was diagnosed in 39 patients, on the basis of clinical and auxological parameters and on the serum concentration of IGF-1, and non-GHD in the other 11 patients. Two PhT GH (arginine and clonidine) were carried out in the 50 patients. Serum GH was determined by two different methods: one detecting most of serum GH isoforms, named Total GH (HGH Bio-Tech, MAIA Clone), and another one, only detecting the 22 kDa GH, named 22K GH (GH-22K IFMA, Wallac). Results: Basal data: all patients with GHD and with non-GHD had maximal serum GH response (MaxR) values below and above the cut-off, respectively, for the serum Total GH and 22K GH. The mean 22K GH/Total GH ratio was similar to previous publications. Post-rhGH treatment data: the two groups improved their height SDS during the first year of treatment, particularly patients with GHD. A receiver-operator curve was used to define the best threshold for post-treatment GV-SDS that separates GHD from non-GHD patients. This value was 1.91 GV-SDS. A negative correlation between first year treatment GV-SDS and pre-treatment serum GH MaxR was found for the two assays (p < 0.001). Then, the best cut-off GV-SDS, previously calculated with the receiver-operator curve (1.91 SDS) was used to interpolate the corresponding serum GH values, as determined by the two methods. For Total GH, the value was 10.8 ng/ml, and for 22K GH, it was 5.4 ng/ml. Conclusion: The cut-off values calculated by biological means to separate GHD from non-GHD were remarkably similar to those calculated biochemically (10.0 and 4.8 ng/ml, respectively) for Total and 22K GH. This is a biological validation for using different cut-off values, appropriate for each assay, to diagnose GHD.
Plasticity of Auditory Medullary-Midbrain Connectivity across Metamorphic Development in the Bullfrog, Rana catesbeiana
Authors: Horowitz Seth S. , Chapman Judith A. , Simmons Andrea Megela
Published: August 2006

On the basis of patterns of anterograde, retrograde, and bi-directional transport of tracers from both the superior olivary nucleus (SON) and the torus semicircularis (TS), we report anatomical changes in brainstem connectivity across metamorphic development in the bullfrog, Rana catesbeiana. In early and late stages of larval development (Gosner stages 25–37), anterograde or bi-directional tracers injected into the SON produce terminal/fiber label in the contralateral SON and in the ipsilateral TS. Between stages 38–41 (deaf period), only sparse or no terminal/fiber label is visible in these target nuclei. During metamorphic climax (stages 42–46), terminal/fiber label reappears in both the contralateral SON and in the ipsilateral TS, and now also in the contralateral TS. Injections of retrograde tracers into the SON fail to label cell bodies in the ipsilateral TS in deaf period animals, mirroring the previously-reported failure of retrograde transport from the TS to the ipsilateral SON during this developmental time. Bilateral cell body label emerges in the dorsal medullary nucleus and the lateral vestibular nucleus bilaterally as a result of SON transport during the late larval period, while cell body label in the contralateral TS emerges during climax. At all larval stages, injections into the SON produce anterograde and retrograde label in the medial vestibular nucleus bilaterally. These data show anatomical stability in some pathways and plasticity in others during larval development, with the most dramatic changes occurring during the deaf period and metamorphic climax. Animals in metamorphic climax show patterns of connectivity similar to that of froglets and adults, indicating the maturation during climax of central anatomical substrates for hearing in air.
Co-Localization of Susceptibility Loci for Psoriasis (PSORS4) and Atopic Dermatitis (ATOD2) on Human Chromosome 1q21
Authors: Giardina Emiliano , Sinibaldi Cecilia , Chini Loredana , Moschese Viviana , Marulli Giorgiana , Provini Alessia , Rossi Paolo , Paradisi Mauro , Chimenti Sergio , Galli Elena , Brunetti Ercole , Girolomoni Giampiero , Novelli Giuseppe
Published: August 2006

Psoriasis (PS) is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and altered differentiation. Atopic dermatitis (ATOD) is a chronic inflammatory, pruritic and eczematous disease frequently associated with respiratory atopy. These diseases are associated with distinct immunologic abnormalities and represent typical examples of complex diseases triggered by both genetic and environmental factors, as demonstrated by independent twin studies. Genome wide linkage studies have mapped susceptibility loci on several chromosomes (PSORS1–9; ATOD1–5). Four of them overlap on chromosomes 1q21, 3q21, 17q25 and 20p although ATOD is quite distinct from PS and these two diseases rarely occur together in the same patient. An association fine-mapping study has been performed to refine PSORS4 and ATOD2 susceptibility loci on chromosome 1q21 analyzing two independently collected cohorts of 128 PS and 120 ATOD trios. Genotype and haplotype analysis of PSORS4 and ATOD2 led us to detect significant p value for haplotypes defined by MIDDLE and ENDAL16 markers in both PS (p = 0.0000036) and ATOD (p = 0.0276), suggesting a strict co-localization within an interval of 42 kb. This genomic interval contains a single gene, LOR, encoding for loricrin. Polymorphic markers mapping in regulatory and coding regions did not show evidence of association in neither of the two diseases. However, expression profiles of LOR in skin biopsies have shown reduced levels in PS and increased levels in ATOD, suggesting the existence of a specific misregulation in LOR mRNA production.
Effects of Early High-Dose Levothyroxine Treatment on Auditory Brain Event-Related Potentials at School Entry in Children with Congenital Hypothyroidism
Authors: Marti S. , Alvarez M. , Simoneau-Roy J. , Leroux S. , van Vliet G. , Robaey P.
Published: August 2006

Aims: We tested whether brain event-related potentials (ERPs) are normal in children with congenital hypothyroidism (CH) after early high-dose levothyroxine treatment. Methods: Auditory ERPs were recorded in 33 normal controls and in 15 children with CH at 5 years 9/12. Based on bone maturation at diagnosis, the CH group was divided into severe (n = 8) and moderate (n = 7) subgroups. CH patients were treated at a median age of 14 days with a mean initial dose of levothyroxine of 11.6 µg/kg·day. Two ERP components (N100 and N200) were measured and clinical follow-up variables collected. Results: The functional anatomical and cognitive organisation of the auditory system, as revealed by the analyses of ERP measures, did not differ between CH and controls, or between severe and moderate CH subjects. However, N200 latency was globally longer in the CH than in the control group (p = 0.01) and was positively correlated with the over-treatment index (r = 0.61; p < 0.05) and verbal IQ. N200 amplitude was negatively correlated with initial dose (r = –0.74; p < 0.005). Conclusion: These data suggest that sensitive tools such as ERPs can reveal differences between CH and controls and relate these differences to the adequacy of treatment of CH.
Role of Glyceryl Trinitrate, a Nitric Oxide Donor, in the Renal Ischemia-Reperfusion Injury of Rats
Authors: Kucuk Hasan Fehmi , Kaptanoglu Levent , Ozalp Figen , Kurt Necmi , Bingul Sadık , Torlak Oguzhan Aziz , Colak Elif , Akyol Huseyin , Gul Aylin Ege
Published: August 2006

Background/Aims: Ischemia-reperfusion injury is a serious clinical situation which can cause serious morbidity and mortality. An experimental renal ischemia-reperfusion injury model was designed to evaluate the role of glyceryl trinitrate (GTN) on renal function and histology. Methods: 50 Wistar albino rats were used in our study. Five groups were formed: (1) sham-control group; (2) acute renal ischemia (ARI) group with placebo (0.9% NaCl) infusion; (3) GTN infusion with a 75 µg/kg/min dose prior to ARI was administered; (4) GTN infusion with a 150 µg/kg/min dose prior to ARI was given, and finally (5) 150 µg/kg/min GTN infusion after the ARI period was applied. Serum BUN and creatinine levels were measured for evaluation of renal function. Tmax-sec, glomerular filtration rate (GFR), and Tmax-min results following a 99mTc-DTPA diuretic renal scintigraphy were used. Histological examination was performed on nephrectomy specimens. Results: Groups 2 and 5 showed higher BUN, creatinine, and lower GFR values than the other groups (p = 0.0001). There was no difference in BUN, creatinine, and GFR levels between groups 2 and 5 (p = 0.971, p = 0.739, p = 0.393). Also the Tmax-sec values were higher in groups 2 and 5 compared with the other groups (p = 0.0001). The presence of tubular necrosis was different between groups and was higher in groups 2 and 5 (p = 0.002). Conclusion: The application of GTN, a nitric oxide donor, has caused significant improvement in renal function when applied prior to an experimentally designed renal ischemia-reperfusion model. But administration of GTN had no effect after occurrence of ischemia.
Detection of Lymphatic Invasion in Early Stage Primary Colorectal Cancer with the Monoclonal Antibody D2-40
Authors: Walgenbach-Bruenagel G. , Tolba R.H. , Varnai A.D. , Bollmann M. , Hirner A. , Walgenbach K.J.
Published: August 2006

Purpose: The purpose of this study was to investigate the presence of lymphatic invasion detected by D2-40 immunostaining compared to conventional hematoxylin-eosin (HE) staining in primary colorectal cancer (CRC) and the development of focal new lymphangiogenesis and peritumoral lymphatic proliferation in relation to the tumor stages. Additionally, we analyzed the relation of peritumoral inflammatory reaction (PIR) to tumor stages in CRC. The identification of new categories of patients with high-risk CRC would be very helpful in improving treatment strategies and patient outcome especially in early CRC. Patients and Method: Biopsies were taken from 41 patients with colorectal adenocarcinomas at different stages of disease. Immunohistochemistry was performed on paraffin-embedded sections. First, the whole section was screened for the presence of lymphatic invasion and PIR with routine HE staining. After analysis of the HE-stained slides, the slides were destained and reused for immunohistochemistry with the D2-40 monoclonal antibody. D2-40-immunostained sections were screened for the presence of lymphatic invasion, the proliferation of lymphatic vessels and focally newly developed lymph vessels. Results: Using the D2-40 antibody for immunostaining, our results demonstrate a significantly higher detection (p < 0.05) of lymphatic vessel invasion compared to routine HE staining in primary CRC. 22% more patients with lymphatic vessel invasion could be identified compared to routine HE staining, especially in node-negative tumor stage (UICC II). The positive predictive value of lymphatic invasion evaluated by D2-40 immunostaining to predict lymph node metastasis is 92% (negative predictive value 81%). High PIR was shown in UICC stage I and II. These infiltrations were rarely seen in UICC stage III and were absent in UICC stage IV. Higher UICC tumor stage is associated with a higher rate of focally newly developed lymphatic vessels. In UICC stage I we found peritumoral lymphatic vessel proliferation only in one case (14%) and in UICC stage II no case was found. 47% of the cases in UICC stage III and 50% of the cases in UICC stage IV showed focal peritumoral lymphatic vessel proliferation. Conclusions: Immunostaining with D2-40 significantly increased the detection rate of lymphatic invasion compared to conventional HE staining in primary CRC. The D2-40 antibody specific for lymphatic endothelium cells has the potential for a prognostic marker in early stage CRC. Further prospective studies are necessary to evaluate the prognostic value of lymphatic invasion and the induction of tumor lymphangiogenesis and its role in human cancer progression.
Treatment with Cyclohexenonic Long-Chain Fatty Alcohol Reverses Diabetes-Induced Tracheal Dysfunction in the Rat
Authors: Hanada Takuya , Saito Motoaki , Kanzaki Susumu
Published: August 2006

In this study, we tried to elucidate the effect of cyclohexenonic long-chain fatty alcohol (N-hexacosanol) on tracheal dysfunction in diabetic rats. Diabetes was induced in 8-week-old male Sprague-Dawley rats by administering an intraperitoneal injection of 50 mg/kg streptozotocin. Non-diabetic control rats received an injection of citrate-phosphate buffer alone. Four weeks after the induction of diabetes, rats were randomly divided into 5 groups: age-matched non-diabetic control rats (group A); 4-week diabetic rats without N-hexacosanol treatment (group B); diabetic rats treated with vehicle (group C), and diabetic rats treated with N-hexacosanol at a dose of 2 or 8 mg/kg i.p. every day for the following 4 weeks (group D and group E, respectively; n = 6–8 animals in each group). Serum glucose and insulin levels were determined, as were the contractile responses induced by carbachol and 100 mmol/l KCl. The participation of M2 and M3 receptors was investigated in the trachea by real-time polymerase chain reaction (PCR), hematoxylin and eosin (HE) and immunohistochemical staining. Hypertrophy of airway smooth muscle was observed in diabetic rats, and was ameliorated by treatment with N-hexacosanol. Treatment with either 2 or 8 mg/kg N-hexacosanol did not alter diabetic rat status, i.e., body weight, serum glucose or serum insulin levels, but it significantly reversed the decrease in tracheal wall thickness and diabetes-induced hypercontractility in the rat trachea. In the immunohistochemical studies, muscarinic M2 and M3 receptors were expressed in the airway smooth muscle, the elastic fibers, the fibroblast and the surface of epithelium, and these expressions were not altered by either induction of diabetes or N-hexacosanol treatment. The expression of M3 muscarinic receptor mRNAs in the trachea tended to be increased by the induction of diabetes and normalized when treated with N-hexacosanol. Our data indicate that N-hexacosanol could reverse diabetes-induced hypercontractility in the rat trachea.
Purifying Japan's Banks: Issues and Implications
Authors: Morck Randall , Yeung Bernard
Published: August 2006

We use a simple real options framework and empirical data to establish that although Japanese banks hold borrowers' shares, their interest is more along the lines of a contractual claimant than a residual claimant of corporations. We then explain why the Japanese model of corporate governance was useful during the “catching-up” growth of that country's postwar reconstruction decades but became problematic subsequently. The interests of shareholders, creditors, workers, and managers are more readily aligned because such growth entails investment in knowntechnology physical-capital-intensive projects with highly predictable cash flows. Once firms are on the technological frontier, “keeping-up” growth requires risk taking and a tolerance for “creative destruction.” This is better accommodated by entrusting corporate governance to firms' true residual claimants, their shareholders.
Macroeconomic Policies and Performance in Iran
Authors: Komijani Akbar
Published: August 2006

This paper reviews Iran's macroeconomic policies and performances during the last 3 decades, starting with the macroeconomic situation before the Islamic Revolution in 1979. Iran emerged from the 8-year war with Iraq in 1988 with a highly centralized economy. Iran then initiated an ambitious reconstruction program of three Five-Year Economic, Social, and Cultural Development Plans (FYDPs). The Third FYDP was a growth-oriented macroeconomic management program that led to the rapid growth of the non-oil sector, a decline in the unemployment rate, a reduction in external debt, accumulation of official international foreign reserves, and improvements in key social indicators. The key challenges facing Iran's economy are highlighted and some distinctive features of the Fourth FYDP (for 2005–2009) are summarized.
SOCS up-regulation mobilizes autologous stem cells through CXCR4 blockade
Authors: Pello Oscar M. , del Carmen Moreno-Ortiz María , Rodríguez-Frade José Miguel , Martínez-Muñoz Laura , Lucas Daniel , Gómez Lucio , Lucas Pilar , Samper Enrique , Aracil Miguel , Martínez-A Carlos , Bernad Antonio , Mellado Mario
Published: August 2006

The chemokine CXCL12 influences self-renewal and differentiation of hematopoietic stem cell precursors in bone marrow by directing them toward specific stromalcell components. CXCL12 up-regulates members of the SOCS family through JAK/STAT activation, a mechanism that attenuates chemokine responses. SOCS expression may thus modulate retention of hematopoietic precursors (Sca-1+ c-Kit+Lin– cells) in bone marrow. We show that in bovine growth hormone transgenic mice and in growth hormone–treated mice, SOCS up-regulation correlated with a large number of Sca-1+ c-Kit+Lin– cells in blood. Retroviral transduction of SOCSs blocked in vitro migration of Sca-1+c-Kit+Lin– cells, as well as their capacity to reconstitute lethally irradiated mice. Furthermore, in lethally irradiated mice reconstituted with bone marrow infected by a tetracycline-regulated, SOCS-expressing lentiviral vector, doxycycline treatment promoted rapid, extensive precursor mobilization to the periphery. The results indicate that by blocking CXCR4-mediated functions, SOCSs modulate hematopoietic precursor cell retention in bone marrow, and suggest the therapeutic interest of SOCS manipulation in several pathologic situations.