bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels
Authors: Navarro-Lérida Inmaculada , Portolés María Teresa , Barrientos Alberto Álvarez , Gavilanes Francisco , Boscá Lisardo , Rodríguez-Crespo Ignacio
Published: March 2004

Several cell types express inducible nitric oxide synthase (NOS2) in response to exogenous insults such as bacterial lipopolysaccharide (LPS) or proinflammatory cytokines. For instance, muscular cells treated with LPS and interferon γ (IFN-γ) respond by increasing the mRNA and protein levels of NOS2, and synthesize large amounts of nitric oxide. We show here that transcriptional induction of NOS2 in muscular cells proceeds with a concomitant decrease in the levels of caveolin-1, -2 and -3. Addition of ·NO-releasing compounds to C2C12 muscle cells reveals that this downregulation of the caveolin (cav) levels is due to the presence of ·NO itself in the case of caveolin-3 and to the action of the LPS/IFN-γ in the case of cav-1 and cav-2. Likewise, muscle cells obtained from NOS2-/- knockout mice challenged with LPS/IFN-γ could downregulate their levels of cav-1 but not of cav-3, unlike wild-type animals, in which both cav-1 and cav-3 levels diminished in the presence of the proinflammatory insult. Laser confocal immunofluorescence analysis proves that ·NO exerts autocrine and paracrine actions, hence diminishing the cav-3 levels. When the induced NOS2 was purified using an affinity resin or immunoprecipitated from muscular tissues, it appears strongly bound not only to calmodulin but also to cav-1, and marginally to cav-2 and cav-3. When the cav levels where reduced using antisense oligonucleotides, an increase in the NOS2-derived ·NO levels could be measured, demonstrating the inhibitory role of the three cav isoforms. Our results show that cells expressing NOS2 diminish their cav levels when the synthesis of ·NO is required.
The small GTPase Rab27B regulates amylase release from rat parotid acinar cells
Authors: Imai Akane , Yoshie Sumio , Nashida Tomoko , Shimomura Hiromi , Fukuda Mitsunori
Published: March 2004

Small GTPase Rab is a large family of putative membrane trafficking proteins, and each member is thought to regulate a specific type(s) of membrane trafficking. However, little is known about the involvement of Rab protein(s) in secretory granule exocytosis in exocrine cells or the molecular mechanism underlying this process. We show that Rab27B, a closely related isoform of Rab27A that regulates lysosome-related granule exocytosis in cytotoxic T lymphocytes, is abundantly expressed on amylase-containing secretory granules in rat parotid gland acinar cells. We also identify the putative Rab27B effector protein, Slac2-c (Slp homologue lacking C2 domains-c)/MyRIP, which was originally described as a myosin Va/VIIa and actin binding protein, in rat parotid glands. The results of subcellular fractionation, immunoprecipitation and immunohistochemical studies indicate that the Rab27B–Slac2-c complex is formed on secretory granules in vivo. The introduction of either a specific Rab27 binding domain (i.e. a recombinant Slp homology domain of Slac2-b that specifically binds Rab27A/B but not other Rabs) or functionally blocking antibodies that specifically disrupt Rab27B–Slac2-c complex in vitro strongly inhibited isoproterenol-stimulated amylase release from streptolysin O-permeabilized parotid acinar cells. Our results indicate that the Rab27B–Slac2-c complex is an important constituent of secretory granule exocytosis in parotid acinar cells.
Syntaxin 8 impairs trafficking of cystic fibrosis transmembrane conductance regulator (CFTR) and inhibits its channel activity
Authors: Bilan Frédéric , Thoreau Vincent , Nacfer Magali , Dérand Renaud , Norez Caroline , Cantereau Anne , Garcia Martine , Becq Frédéric , Kitzis Alain
Published: March 2004

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-dependent chloride channel that mediates electrolyte transport across the luminal surface of epithelial cells. In this paper, we describe the CFTR regulation by syntaxin 8, a t-SNARE protein (target soluble N-ethylmaleimide-sensitive factor attachment protein receptor) involved in the SNARE endosomal complex. Syntaxin family members are key molecules implicated in diverse vesicle docking and membrane fusion events. We found that syntaxin 8 physically interacts with CFTR: recombinant syntaxin 8 binds CFTR in vitro and both proteins co-immunoprecipitate in HT29 cells. Syntaxin 8 regulates CFTR-mediated currents in chinese hamster ovary (CHO) cells stably expressing CFTR and syntaxin 8. Iodide efflux and whole-cell patch-clamp experiments on these cells indicate a strong inhibition of CFTR chloride current by syntaxin 8 overexpression. At the cellular level, we observed that syntaxin 8 overexpression disturbs CFTR trafficking. Confocal microscopy shows a dramatic decrease in green fluorescent protein-tagged CFTR plasma membrane staining, when syntaxin 8 is coexpressed in COS-7 cells. Using antibodies against Lamp-1, TfR or Rab11 we determined by immunofluorescence assays that both proteins are mainly accumulated in recycling endosomes. Our results evidence that syntaxin 8 contributes to the regulation of CFTR trafficking and chloride channel activity by the SNARE machinery.
The arithmetic of centrosome biogenesis
Authors: Delattre Marie , Gönczy Pierre
Published: March 2004

How do cells regulate centrosome number? A canonical duplication cycle generates two centrosomes from one in most proliferating cells. Centrioles are key to this process, and molecules such as centrins, SAS-4 and ZYG-1 govern daughter centriole formation. Cdk2 activity probably couples centrosome duplication with the S phase, and a licensing mechanism appears to limit centrosome duplication to once per cell cycle. However, such mechanisms must be altered in some cells – for example, spermatocytes – in which centrosome duplication and DNA replication are uncoupled. There are also alternative pathways of centrosome biogenesis. For example, one centrosome is reconstituted from two gametes at fertilization; in this case, the most common strategy involves differential contributions of centrioles and pericentriolar material (PCM) from each gamete. Furthermore, centrioles can sometimes form de novo from no apparent template. This occurs, for instance, in the early mouse embryo and in parthenogenetic species and might rely on a pre-existing seed that resides within PCM but is not visible by ultrastructural analysis.
Photomagnetic Co–Fe Prussian Blue Thin Films Fabricated by the Modified Langmuir–Blodgett Technique
Authors: Yamamoto Takashi , Umemura Yasushi , Sato Osamu , Einaga Yasuaki
Published: March 2004

Co–Fe Prussian blue thin films have been prepared by means of a modified Langmuir–Blodgett technique, in which the hybrid monolayer composed of amphiphiles and clay platelets plays a template role for the formation Co–Fe Prussian blue thin films. Photoinduced magnetization was observed in the thin films as observed in the bulk Co–Fe Prussian blue. To the best of our knowledge, this is the first example of successful formation of Co–Fe Prussian blue thin films, which possess the ordered structure and, in addition, exhibit photoinduced magnetization.
A model of chronic heart failure in spontaneous hypertensive rats (SHR)
Authors: Itter G. , Jung W. , Juretschke P. , Schoelkens B. A. , Linz W.
Published: March 2004

Common models of chronic heart failure (CHF) do not always result in parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The aim of this study was to establish and validate a new model of CHF in the rat. CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive (SHR/NHsd) rats by creating a permanent (8-week) occlusion of the left coronary artery 2 mm distal to the origin from the aorta by a modified technique. This resulted in a large infarction of the free left ventricular wall. The focus of attention was the validation of the geometric properties of the left ventricle and its contractility. The validation of the geometric properties of the left ventricle was done by a non-invasive magnetic resonance imaging (MRI) technique and by planimetry (stereology). Cardiodynamics (e.g. contractility) were evaluated in the isolated 'working heart' model. We were able to establish a new and predictive model of heart failure in the spontaneously hypertensive rat 8 weeks after coronary artery ligation. At this time point, the WKY rat did not show any symptoms of CHF. The model represents characteristic parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III–IV). Upon inspection, severe clinical symptoms of congestive heart failure were prominent, such as dyspnoea, subcutaneous oedema, pale-bluish limbs and impaired motion. Non-invasive sequential measurements by NMR techniques showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. The infarcted animals showed a reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd rat than in the WKY/NHsd rat. Furthermore the infarcted animals showed enhanced levels of hydroxyproline/proline ratios, again much more so in the SHR/NHsd rat than in the WKY/NHsd rat.
Laparoscopy of rats with experimental liver metastases: a method to assess new humane endpoints
Authors: Kobaek-Larsen Morten , Rud Lene , Oestergaard Soerensen Finn , Ritskes-Hoitinga Jelmera
Published: March 2004

Metastatic disease to the liver is one of the major factors determining the outcome of colonic resection with curative interventions in human patients. Therefore, animal models for studies of liver metastasis have been developed. Humane endpoints are needed for the evaluation of the animal condition. Liver metastases were modelled by hepatic subcapsular injection of a syngeneic rat colon cancer cell line (DHD/K12-PROb) in BDIX/OrlIco rats. In this study, we present a detailed description of a laparoscopic technique for the direct inspection of liver metastases. That way a qualitative impression of the metastases was obtained. We suggest, as a new humane endpoint, that one animal should only have 1–2 separately growing metastases, each of a maximum size of 10 mm2. In future, the method has to be developed further to measure the size of the metastases in a more quantitatively precise manner. Although the animal has to be anaesthetized each time, laparoscopy is considered a minor surgical procedure as only two small puncture wounds are made through the abdominal wall. Because laparoscopy offers a direct view of the hidden tumours and their sizes, as well as of possible complications (e.g. peritoneal tumour growth), one can prevent unnecessary discomfort. We therefore think the advantages outweigh the disadvantages, as laparoscopy helps to avoid the unnecessary suffering due to large tumours which may only be detected at late stages by conventional procedures.
Long-term effects of husbandry procedures on stress-related parameters in male mice of two strains
Authors: Van Loo P. L. P. , Van der Meer E. , Kruitwagen C. L. J. J. , Koolhaas J. M. , Van Zutphen L. F. M. , Baumans V.
Published: March 2004

In socially unstable groups of male laboratory mice, individuals may experience a chronic stress situation. Previous experiments have shown that the transfer of specific olfactory cues during cage cleaning, and the provision of nesting material decrease aggression and stress in group-housed male mice. In this study, the combined effect of these husbandry procedures were tested for their long-term effect on stress in groups of moderately aggressive (BALB/c) and severely aggressive (CD-1) male mice. The physiological and behavioural stress-related parameters used were body weight, food and water intake, spleen and thymus weight, adrenal tyrosine hydroxylase activity, urine corticosterone levels and behaviour in a cage emergence test. Long-term provision of nesting material and its transfer during cage cleaning was found to influence several stress-related physiological parameters. Mice housed in cages enriched with nesting material had lower urine corticosterone levels and heavier thymuses, and they consumed less food and water than standard-housed mice. Furthermore, marked differences were found between strains. CD-1 mice were less anxious in the cage emergence test, weighed more, ate and drank more, and had heavier thymuses but lighter spleens and lower corticosterone levels than BALB/c mice. We conclude that the long-term provision of nesting material, including the transfer of nesting material during cage cleaning, reduces stress and thereby enhances the welfare of laboratory mice.
Weight Gain Mitigation with Topiramate in Mood Disorders
Authors: Woods Tonja M , Eichner Samantha F , Franks Andrea S
Published: March 2004

OBJECTIVE

To review the evidence of weight loss with use of topiramate in patients with mood disorders.

DATA SOURCES

Literature search included MEDLINE (1966—December 2003), International Pharmaceutical Abstracts (1970–December 2003), and EMBASE (1980—December 2003). Search terms included topiramate, weight loss, adverse effect, mood disorders, bipolar disorder.

DATA SYNTHESIS

Weight gain is a common adverse effect of many agents used to treat mood disorders. Topiramate has been evaluated in the management of some mood disorders, and weight loss may be a beneficial side effect in these patients. Case reports, letters to the editor, prospective investigations, and retrospective observational studies were reviewed to identify evidence of weight loss with topiramate use in patients with mood disorders.

CONCLUSIONS

Current evidence suggests an association between topiramate and weight loss. Based on the limited data, controlled studies need to be conducted to define the role of topiramate in patients with mood disorders who would also benefit from weight reduction.
Parecoxib for Parenteral Analgesia in Postsurgical Patients
Authors: Amabile Celene M , Spencer Anne P
Published: March 2004

OBJECTIVE

To review the pharmacology, pharmacokinetics, clinical efficacy and safety studies, adverse effects, drug interactions, and dosage and administration of parecoxib sodium, a selective cyclooxygenase-2 (COX-2) inhibitor.

DATA SOURCES

Information was obtained from MEDLINE searches of the English-language literature (1996—May 2003). Search terms included parecoxib, parecoxib sodium, SC-69124A, and selective cyclooxygenase-2 inhibitor.

STUDY SELECTION AND DATA EXTRACTION

We reviewed available literature, which included abstracts, clinical trials, and data on file with the manufacturer.

DATA SYNTHESIS

Parecoxib sodium is a novel selective COX-2 inhibitor under development for parenteral administration. It has produced efficacious analgesia following dental, gynecologic, and orthopedic surgery. The adverse effect profile has been compared with that of ketorolac; no statistically significant differences were identified. There are no documented drug interactions when parecoxib is coadministered with midazolam, propofol, or unfractionated heparin.

CONCLUSIONS

Parecoxib sodium is in the final stages of Phase III trials and has a favorable safety and efficacy profile. Its place in moderate to severe postsurgical pain management will be further defined when more pharmacoeconomic and postmarketing safety data are available. Theoretical benefits are its lower potential for gastrointestinal adverse effects compared with ketorolac and lower opioid requirements after surgery.
Fenoldopam Versus Nitroprusside for the Treatment of Hypertensive Emergency
Authors: Devlin John W , Seta Maria L , Kanji Salmaan , Somerville Allison L
Published: March 2004

BACKGROUND

While sodium nitroprusside remains first-line therapy for hypertensive emergency (HEM), fenoldopam is increasingly being used because of its benign safety profile and potential renal protective effects.

OBJECTIVE

To compare the efficacy, safety, and cost of sodium nitroprusside versus fenoldopam for the treatment of HEM.

METHODS

This study was a retrospective analysis of consecutive patients with HEM admitted to a university-affiliated, level 1 trauma center from 1999 to 2001 and treated with either nitroprusside (n = 21) or fenoldopam (n = 22) for >30 minutes. Time to reach mean arterial pressure (MAP) goal, change in MAP over time, time to initiation of oral antihypertensive therapy, change in renal function, incidence of cyanide toxicity, and cost of therapy were compared between groups.

RESULTS

Demographic parameters were similar between groups, except renal failure, which was more prevalent in the fenoldopam group (10% vs 46%; p = 0.009). Neither the mean ± SD pretreatment MAP (nitroprusside 168 ± 19; fenoldopam 163 ± 19; p = 0.45), time to reach MAP goal (3.6 [0.4–30] vs 4 [1–22] h; p = 0.51), nor infusion duration (18 [0.7–113] vs 18 [3–74] h; p = 0.45) differed between the patient groups. Time to initiation of oral antihypertensive therapy was similar between nitroprusside- (4.5 h [0.5–22] and fenoldopam- (6.5 h [1–100] treated patients; p = 0.65). Additional intravenous antihypertensives were administered to 16 patients in each group (p = 0.80). Change in creatinine clearance and incidence of tachycardia did not differ between groups. No symptoms of cyanide toxicity were detected. Cost of drug therapy was greater with fenoldopam ($597.60, $199.20–6675.20); than nitroprusside ($2.66, $1.68–3.48; p < 0.001).

CONCLUSIONS

Treatment of HEM with fenoldopam appears to result in patient outcomes equivalent to those with nitroprusside but at a substantially higher cost. Further study is required to delineate the exact role of fenoldopam for treatment of HEM.
Thiazolidinedione-Induced Congestive Heart Failure
Authors: Cheng Alice YY , Fantus I George
Published: March 2004

OBJECTIVE

To report 2 cases of thiazolidinedione (TZD)-associated congestive heart failure (CHF). As of March 13, 2004, one of the cases may represent the first description of TZD-associated cardiomyopathy in humans.

CASE SUMMARIES

A 57-year-old obese white man with type 2 diabetes was treated with pioglitazone 30 mg/day and insulin. He had no prior history of CHF and had an excellent exercise tolerance. Over the first 4 weeks of pioglitazone therapy, the patient experienced significant weight gain and subsequently developed CHF and pulmonary edema. A 50-year-old obese white man with type 2 diabetes presented with cardiogenic shock. Rosiglitazone 4 mg once daily had been initiated 6 weeks prior to presentation. He had no prior history of cardiac disease, and investigations did not reveal a cause for the cardiogenic shock. Rosiglitazone therapy was discontinued on admission. He improved and was discharged 21 days later.

DISCUSSION

TZDs are oral agents used for the treatment of type 2 diabetes. TZD-associated CHF and pulmonary edema have been reported in patients with a prior history of CHF. These 2 cases highlight that this adverse event can occur even in the absence of any preexisting history of clinical heart failure or cardiac disease. The second case may represent the first description of TZD-associated cardiomyopathy in humans. In both cases, an objective causality assessment using the Naranjo probability scale revealed that the adverse drug reaction between cardiomyopathy and rosiglitazone in this patient was probable.

CONCLUSIONS

TZD should be considered as a cause in the differential diagnosis of CHF and pulmonary edema in patients without a prior history of clinical CHF or cardiac disease. Healthcare professionals should be aware of the possible association between TZDs and cardiomyopathy.
Holo-Transcobalamin Concentration and Transcobalamin Saturation Reflect Recent Vitamin B12 Absorption Better than Does Serum Vitamin B12
Authors: Bor Mustafa Vakur , Nexø Ebba , Hvas Anne-Mette
Published: March 2004

Background: We evaluated whether measurement of vitamin B12-saturated transcobalamin (holo-TC) concentrations or TC saturation (holo-TC:total TC) reflects active vitamin B12 absorption in healthy individuals and patients after vitamin B12 intake.

Methods: We obtained blood samples from 31 healthy individuals (age range, 25–57 years) before (days −1 and 0) and after (days 1, 2, and 6) oral administration of three 9-μg doses of vitamin B12. The blood samples from seven patients (age range, 22–39 years) suspected to have decreased vitamin B12 absorption were obtained before and 1 day after the vitamin B12 intake. The blood samples were analyzed for vitamin B12, total TC, and holo-TC. The TC saturation was calculated.

Results: Intraindividual variation was <13% for all measured values, as calculated from samples removed on day −1 and 0. In healthy individuals (n = 31) after intake of vitamin B12, the maximum median (range) increase (as percentages and absolute values) was in TC saturation [52 (−2% to 128)% and 0.04 (0–0.23) as a fraction], closely followed by holo-TC concentrations [39 (0–108)% and 34 (0–149) pmol/L]. All but one healthy individual had an increase of ≥15% in these markers. Serum vitamin B12 showed a smaller increase [14 (−8 to 51)% and 36 (−27 to 290) pmol/L]. After vitamin B12 intake, three patients with Crohn disease had the lowest increases in holo-TC concentration (3, 7, and 14 pmol/L) and in TC saturation (0.004, 0.01, and 0.01) among patients and 30 healthy individuals.

Conclusion: Holo-TC concentrations and TC saturation reflect normal vitamin B12 absorption better than does serum vitamin B12.
Blind separation of delayed instantaneous mixtures: a cross‐correlation based approach
Authors: Z. Ikram Muhammad
Published: March 2004

A cross‐correlation based method is proposed for blind separation of statistically uncorrelated i.i.d. signals. In contrast to much of the existing work in the area, the proposed method allows the separation of more sources than sensors and the sensors are not restricted to have non‐Gaussian distributions. The mixed signals are modelled as a sum of attenuated and delayed source signals. As compared to the delayless mixture model commonly employed in the literature, incorporating delays in the model may offer better fit to practical applications, such as source separation in an anechoic environment. We estimate the delay and attenuation parameters from the peak locations and strengths of the cross‐correlation function, respectively. Using these parameters, we then discuss the use of four methods for the recovery of source signals. These methods are compared and their usage is proposed under different operating conditions. Copyright © 2004 John Wiley & Sons, Ltd.
Blind separation of convolutive mixtures of cyclostationary signals
Authors: Wang Wenwu , Jafari Maria G. , Sanei Saeid , Chambers Jonathon A.
Published: March 2004

An adaptive blind source separation algorithm for the separation of convolutive mixtures of cyclostationary signals is proposed. The algorithm is derived by applying natural gradient iterative learning to a novel cost function which is defined according to the wide sense cyclostationarity of signals and can be deemed as a new member of the family of natural gradient algorithms for convolutive mixtures. A method based on estimating the cycle frequencies required for practical implementation of the proposed algorithm is presented. The efficiency of the algorithm is supported by simulations, which show that the proposed algorithm has improved performance for the separation of convolved cyclostationary signals in terms of convergence speed and waveform similarity measurement, as compared to the conventional natural gradient algorithm for convolutive mixtures. Copyright © 2004 John Wiley & Sons, Ltd.
Severe hemolytic anemia due to cold agglutinin complicating untreated chronic hepatitis C: Efficacy and safety of anti‐CD20 (rituximab) treatment
Authors: Etienne Anne , Gayet Stéphane , Vidal Florian , Poullin Pascale , Brunet Corinne , Harlé Jean‐Robert , Kaplanski Gilles
Published: March 2004

Autoimmune hemolytic anemia (AIHA) is rare and difficult to treat during chronic hepatitis C. We report herein the case of a hepatitis C patient with severe and resistant AIHA who experienced a good and sustained response with anti‐CD20 monoclonal antibody treatment. Am. J. Hematol. 75:243–245, 2004. © 2004 Wiley‐Liss, Inc.
Direct demonstration of iron in a term placenta in two cases of β‐thalassemia
Authors: Artico M. , Ballati G. , Bosco S. , Cantarelli D. , Nagar G. , Grosso A. , Leali F.M. Tranquilli , Cavallotti C.
Published: March 2004

The aim of this study was to quantify iron in the placentas at the end of pregnancy in two patients suffering from β‐thalassemia and compare the data to that recorded from the placentas of healthy women. Iron was quantified in placental specimens taken after the delivery. The specimens were subjected to chemical treatments in order to remove extracellular iron and leave the intracellular iron intact. After coloration, each specimen was subjected to quantitative analysis of images in order to identify and quantify iron. Our results demonstrated that in β‐thalassemia there is an accumulation of iron in the outer basal cytoplasm of the epithelial cells of placental cotyledons. Am. J. Hematol. 75:241–242, 2004. © 2004 Wiley‐Liss, Inc.
Free immunoglobulin light‐chain serum levels in the follow‐up of patients with monoclonal gammopathies: Correlation with 24‐hr urinary light‐chain excretion
Authors: Alyanakian Marie‐Alexandra , Abbas Aïcha , Delarue Richard , Arnulf Bertrand , Aucouturier Pierre
Published: March 2004

In patients with light‐chain myeloma or primary AL‐amyloidosis, 24‐hr light‐chain excretion in the urine is considered an essential marker of the tumor mass. However, 24‐hr urine collection and analysis may be cumbersome and prone to inaccuracy. Recently, a sensitive immunonephelometric assay for immunoglobulin free light chains (FLC) in the serum was developed. We sought to determine whether the serum level of monoclonal FLC could be used as an indicator of urinary excretion and disease evolution. Seven patients with light‐chain myeloma and AL‐amyloidosis were studied, all of which had a monoclonal FLC that could be detected in the urine using standard methods. In four of these patients, follow‐up revealed a remarkable correlation between FLC serum levels and daily urinary excretions. The ratio of serum level to urinary light‐chain excretion, although stable in a given patient, was extremely variable between patients. In the three remaining cases featuring hardly measurable amounts of light chain in the urine, the serum FLC assay proved sensitive enough for correlation with clinical events. Thus, immunonephelometric measurement of serum FLCs is a reliable method for the follow‐up of patients with light‐chain secreting monoclonal gammopathies. Am. J. Hematol. 75:246–248, 2004. © 2004 Wiley‐Liss, Inc.
Pappenheimer bodies: A brief historical review
Authors: Sears David A. , Udden Mark M.
Published: March 2004

Pappenheimer is credited with describing the intraerythrocytic collections of iron, or siderotic granules, as they appear on Wright‐stained blood smears of certain patients after splenectomy. The history of their description and elucidation of their origin and disposition shows the interaction of morphology with the increasing understanding of red cell physiology in the mid‐twentieth century. Am. J. Hematol. 75:249–250, 2004. © 2004 Wiley‐Liss, Inc.
Unrelated peripheral blood and cord blood hematopoietic stem cell transplants for thalassemia major
Authors: Tan Patrick Huat‐Chye , Hwang William Ying Khee , Goh Yeow Tee , Tan Poh Lin , Koh Liang Piu , Tan Cheng Hoe , Quah Thuan Chong
Published: March 2004

Allogeneic hematopoietic stem cell transplantation is currently the only curative treatment available for thalassemia major. While sibling donors are usually used, unrelated bone marrow transplants have also recently been found to be successful. In this report of two patients, we show that, besides using unrelated bone marrow, peripheral blood stem cell and cord blood transplantations from unrelated donors are viable options. We believe a significant contributory factor in both our cases was the large cell dose used. Am. J. Hematol. 75:209–212, 2004. © 2004 Wiley‐Liss, Inc.
Nodular regenerative hyperplasia of the liver: An under‐recognized cause of portal hypertension in hematological disorders
Authors: Al‐Mukhaizeem Khalid A. , Rosenberg Arthur , Sherker Averell H.
Published: March 2004

Portal hypertension has been described in a wide variety of hematological disorders, especially myeloproliferative and lymphoproliferative disorders. Its clinical manifestations may include bleeding esophageal varices, ascites, or hepatic encephalopathy. In patients with hematological disorders, there are a number of potential causes of portal hypertension, including nodular regenerative hyperplasia of the liver (NRH). This lesion is characterized by diffuse replacement of normal hepatic parenchyma by multiple small nodules composed of regenerating hepatocytes with minimal or no fibrosis. This lack of fibrosis distinguishes NRH from cirrhosis. Unlike cirrhosis, NRH only rarely results in compromised hepatic synthetic function. The major manifestation is portal hypertension related to increased resistance to blood flow within hepatic sinusoids. NRH has been linked to a variety of systemic diseases including collagen vascular diseases, myeloproliferative and lymphoproliferative disorders, as well as various medications. Although NRH is commonly associated with blood dyscrasias, the diagnosis is overlooked because of the complexity and wide differential diagnosis of liver diseases in the setting of hematological malignancy. We review herein nodular regenerative hyperplasia of the liver, including aspects of epidemiology, pathogenesis, differential diagnosis, clinical course, and treatment. We highlight its association with different forms of hematological disease, aiming to increase the awareness of this entity to the internist and the treating hematologist/oncologist. Am. J. Hematol. 75:225–230, 2004. © 2004 Wiley‐Liss, Inc.
Large deletion of the GJB6 gene in deaf patients heterozygous for the GJB2 gene mutation: Genotypic and phenotypic analysis
Authors: Feldmann Delphine , Denoyelle Françoise , Chauvin Pierre , Garabédian Eréa‐Noël , Couderc Rémy , Odent Sylvie , Joannard Alain , Schmerber Sébastien , Delobel Bruno , Leman Jacques , Journel Hubert , Catros Hélène , Maréchal Cédric Le , Dollfus Hélène , Eliot Marie‐Madeleine , Delaunoy Jean‐Pierre , David Albert , Calais Catherine , Drouin‐Garraud Valérie , Obstoy Marie‐Françoise , Bouccara Didier , Sterkers Olivier , Huy Patrice Tran Ba , Goizet Cyril , Duriez Françoise , Fellmann Florence , Hélias Jocelyne , Vigneron Jacqueline , Montaut Bétina , Lewin Patricia , Petit Christine , Marlin Sandrine
Published: March 2004

Recent investigations identified a large deletion of the GJB6 gene in trans to a mutation of GJB2 in deaf patients. We looked for GJB2 mutations and GJB6 deletions in 255 French patients presenting with a phenotype compatible with DFNB1. 32% of the patients had biallelic GJB2 mutations and 6% were a heterozygous for a GJB2 mutation and a GJB6 deletion. Biallelic GJB2 mutations and combined GJB2/GJB6 anomalies were more frequent in profoundly deaf children. Based on these results, we are now assessing GJB6 deletion status in cases of prelingual hearing loss. © 2004 Wiley‐Liss, Inc.
Two sibs with fibrochondrogenesis
Authors: Leeners Brigitte , Funk Andreas , Cotarelo Christina L. , Sauer Itta
Published: March 2004

Fibrochondrogenesis is one of the rare lethal osteochondrodysplasias, which show abnormal maturation, and disturbed growth of cartilage and bones. These disorders are a heterogenous group of genetic disorders with a total incidence of 1–3 in 10,000 births. Only 13 cases of fibrochondrogenesis have been published since Lazzaroni‐Fossati et al. [1978] first described the disorder. We report on two sibs that occurred in a consanguineous couple and discuss the ultrasonographic, clinical, radiological, and pathological characteristics of this disorder. This occurrence confirms autosomal recessive inheritance of fibrochondrogenesis. © 2004 Wiley‐Liss, Inc.
Discordant phenotypes in first cousins with UBE3A frameshift mutation
Authors: Molfetta G.A. , Muñoz M.V.R. , Santos A.C. , Silva W.A. , Wagstaff J. , Pina‐Neto J.M.
Published: March 2004

Mutations have been found in the UBE3A gene (E6‐AP ubiquitin protein ligase gene) in many Angelman syndrome (AS) patients with no deletion, no uniparental disomy, and no imprinting defect. UBE3A mutations are more frequent in familial than in sporadic patients and the mutations described so far seem to cause similar phenotypes in the familial affected cases. Here we describe two first cousins who have inherited the same UBE3A frameshift mutation (duplication of GAGG in exon 10) from their asymptomatic mothers but present discordant phenotypes. The proband shows typical AS features. Her affected cousin shows a more severe phenotype, with asymmetric spasticity that led originally to a diagnosis of cerebral palsy. Proband's brain MRI shows mild cerebral atrophy while her cousin's brain MRI shows severe brain malformation. This family demonstrates that, although brain malformation is unusual in AS, presence of a brain malformation does not exclude the diagnosis of AS. Also, this UBE3A mutation was transmitted from the cousin's grandfather to only two sisters among eight full siblings, raising the hypothesis of mosaicism for this mutation. © 2004 Wiley‐Liss, Inc.
Risk of sudden death in the Williams–Beuren syndrome
Authors: Wessel Armin , Gravenhorst Verena , Buchhorn Reiner , Gosch Angela , Partsch Carl‐Joachim , Pankau Rainer
Published: March 2004

Williams–Beuren syndrome (WBS) is a genetic disorder characterized by a distinctive facial gestalt, mental retardation, mild growth deficiency, and cardiovascular disease. The occurrence of sudden death in the WBS is known from several case reports, but information about the risk of sudden death as derived from the data of a large cohort of patients is lacking. We analyzed the data of 293 WBS patients who had been treated for 43 years at the same two institutions. We thus collected 5,190 patient years without loss to follow‐up. During this period ten patients died. Five of them died from: reticulosarcoma (1), after accident (1), heart failure (1), following heart surgery (2). Of the remaining five patients, four died suddenly and one died of unknown cause suggestive of sudden cardiac death. Thus, the incidence of sudden death in our WBS cohort amounts to 1/1,000 patient years. This risk of sudden death is comparable to that following surgery for congenital heart disease, and is 25–100‐fold higher compared to the age‐matched normal population. © 2004 Wiley‐Liss, Inc.
Clinical, MRI, and pathological features of polymicrogyria in chromosome 22q11 deletion syndrome
Authors: Sztriha László , Guerrini Renzo , Harding Brian , Stewart Fiona , Chelloug Nora , Johansen Johan G.
Published: March 2004

Polymicrogyria is a brain malformation due to abnormal cortical organization. Two histological types, unlayered or four‐layered can be distinguished. Polymicrogyria is a rare manifestation of chromosome 22q11 deletion syndrome. We report two boys with chromosome 22q11 deletion syndrome and polymicrogyria, and describe the neuropathological features of the malformation in one of them. Clinical examinations, EEG, brain MRI, chromosomal analysis with FISH, and neuropathological studies of surgically resected cortical tissue were performed. Both patients showed severe developmental delay with cardiovascular malformations and one of them had drug resistant epilepsy. Polymicrogyria was found in the frontal, parietal, and temporal areas, unilaterally in one patient and bilaterally in the other. Histology revealed four‐layered polymicrogyria. The pathogenesis of polymicrogyria in 22q11 deletion syndrome is discussed. © 2004 Wiley‐Liss, Inc.
Twenty‐four new cases of WT1 germline mutations and review of the literature: Genotype/phenotype correlations for Wilms tumor development
Authors: Royer‐Pokora Brigitte , Beier Manfred , Henzler Markus , Alam Rita , Schumacher Valérie , Weirich Angela , Huff Vicki
Published: March 2004

We report here 24 new Wilms tumor (WT) patients with germline WT1 alterations and a synopsis of our own previously described and literature cases in whom age of tumor‐onset, gender, and laterality were known. This combined database contains 282 patients, 117 patients with and 165 without WT1 germline alterations. Using this information we have determined the median age of tumor‐onset for patients with (12.5 months) and without WT1 gene alterations (36 months). The earliest onset was in patients with truncation (12 mo, 66 patients), followed by missense mutations (18 mo, 30 patients) and deletions (22 mo, 21 patients). Patients with the two most frequent nonsense mutations R362X and R390X and the Denys–Drash syndrome (DDS) hot spot mutation R394W/Q/L had a very early onset (9, 12, and 18 mo, respectively). The highest number of bilateral tumors was observed in the group of truncation mutations, with a higher percentage of bilateral tumors when truncations occurred in the 5′ half of the WT1 gene. In addition to genital tract anomalies (GU), early onset nephrotic syndrome with diffuse mesangial sclerosis and stromal‐predominant histology, tumor bilaterality, and early age of onset can now be added to the list of risk factors for carrying a germline WT1 mutation. © 2004 Wiley‐Liss, Inc.
Marfanoid habitus with abnormal situs
Authors: Kosaki Kenjiro , Bird Lynne M. , Maeda Jun , Higuchi Masataka , Jones Marilyn C. , Matsumoto Morio
Published: March 2004

Marfanoid habitus suggests abnormal microfibril formation, whereas a situs ambiguus or situs inversus phenotype points to defective left–right axis determination. The concurrence of these two abnormalities has been reported only once in the literature. We report a similar phenotype in two unrelated patients. Documentation of this specific combination of Marfanoid habitus and abnormal situs gives further credence to the notion that the combination may represent a distinct syndrome. © 2004 Wiley‐Liss, Inc.
Valproate therapy and nonalcoholic fatty liver disease
Authors: Luef Gerhard J. , Waldmann Markus , Sturm Wolfgang , Naser Anis , Trinka Eugen , Unterberger Iris , Bauer Gerhard , Lechleitner Monika
Published: March 2004

Nonalcoholic fatty liver disease was defined recently as another symptom of insulin resistance. Continuous therapy with valproate can result in increased body weight and insulin resistance, but no data are yet available on a possible relationship between valproate and nonalcoholic fatty liver disease. We here demonstrate in abdominal ultrasound investigations that characteristics of fatty liver disease were present in 61% of valproate‐treated patients as compared with 23% receiving carbamazepine therapy. Ann Neurol 2004
Crystallographic report: Bi(S2CNC5H10)2(NO3)(1,10‐phenanthroline)
Authors: Yin Handong , Wang Chuanhua
Published: March 2004

The structure of Bi(S2CNC5H10)2(NO3)(1,10‐Phen) features an eight‐coordinated distorted square antiprismatic geometry around bismuth, defined by an N2O2S4 donor set, with BiS distances ranging from 2.641(2) to 2.824(2) Å. Copyright © 2004 John Wiley & Sons, Ltd.
Crystallographic report: Bis[bis(N‐methyl‐N‐phenyldithiocarbamato)‐(methylxanthato)bismuth(III)]
Authors: Yin Han‐Dong , Wang Chuan‐Hua , Wang Yong
Published: March 2004

The centrosymmetric structure of {Bi[S2CN(Me)Ph]2(S2COMe)}2 features chelating dithiocarbamate and xanthate ligands, as well as intermolecular Bi·S interactions, so that a distorted pentagonal bipyramidal S7 coordination geometry results. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis, characterization, X‐ray crystal structure and in vitro antitumour activity of sodium bis(2‐(3′,6′,9′‐trioxadecyl)‐1,2‐dicarba‐closo‐dodecaborane‐1‐carboxylato)triphenylstannate
Authors: Bregadze V. I. , Glazun S. A. , Petrovskii P. V. , Starikova Z. A. , Buyanovskaya A. G. , Takazova R. U. , Gielen M. , de Vos D. , Kemmer M. , Biesemans M. , Willem R.
Published: March 2004

Sodium bis[2‐(3′,6′,9′‐trioxadecyl)‐1,2‐dicarba‐closo‐dodecaborane‐1‐carboxylato]triphenylstannate, [(CH3OCH2CH2OCH2CH2OCH2CH2)‐1,2‐C2B10H10‐9‐COO)2SnPh3]− Na+, compound 1, was synthesized by the 1:1 condensation of triphenyltin(IV) hydroxide with 2‐(3′,6′,9′‐trioxadecyl)‐1,2‐dicarba‐closo‐dodecaborane‐1‐carboxylic acid and crystallized in the presence of sodium bicarbonate. Its structure was determined by spectroscopy, elemental analysis and X‐ray diffraction. The structure of 1 consists of trigonal bipyramidal [Sn(Ph)3(L)2]− anions and Na+ cations coordinated by oxygen atoms of polyoxaalkyl chains of different stannate anions, forming cation–anion chains elongated along the c axis. Compound 1 is significantly more active in vitro against seven tumour cell lines of human origin than 5‐fluorouracil, cis‐platin, carboplatin, and previously reported organotin carboranecarboxylates, but is less active than organotin polyoxaalkylcarboxylates. Copyright © 2004 John Wiley & Sons, Ltd.
Crystallographic report: 2‐Furfurylgermatrane
Authors: Lukevics Edmunds , Ignatovich Luba , Belyakov Sergey
Published: March 2004

The germanium atom is penta‐coordinated and adopts a trigonal bipyramidal geometry. The 2‐furfuryl group and the nitrogen atom each occupy an apical position with a transannular N→Ge bond distance of 2.173(3) Å. Copyright © 2004 John Wiley & Sons, Ltd.
Speciation of essential and toxic elements in edible mushrooms: size‐exclusion chromatography separation with on‐line UV–inductively coupled plasma mass spectrometry detection
Authors: Wuilloud Rodolfo G. , Kannamkumarath Sasi S. , Caruso Joseph A.
Published: March 2004

Size‐exclusion liquid chromatography was coupled to UV and inductively coupled plasma mass spectrometry (ICP‐MS) for detection to perform elemental speciation studies on different edible mushrooms. Molecular weight (MW) distribution patterns of several elements among different fractions present in various edible mushrooms are presented. The association of the elements with the high and low MW fractions was observed using sequential detection by UV and ICP‐MS. Separation was performed using a Superdex 75 column. Variability of the fractionation patterns with three different extraction media (0.05 mol l−1 NaOH; 0.05 mol l−1 HCl; hot water at 60°C) was evaluated for mushroom species. A comparative elemental speciation study was performed in order to determine the differences in the fractionation patterns of silver, arsenic, cadmium, mercury, lead, and tin in Boletus edulis, Agaricus bisporus, and Lentinus edodes. Differences in the fractionation patterns of the elements were found to depend on the mushroom species and the extraction medium. Most of the elements were associated with high mw fractions. It was not possible to assess the trace metal contributions from the mushroom growth media. Copyright © 2004 John Wiley & Sons, Ltd.
Alloyed transition‐metal complexes of tricyanomethide (tcm), [Mn1−xCox(tcm)2]
Authors: Sayaduzzaman Mohammad , Katsuhara Mao , Hoshino Hirotada , Kawamoto Tadashi , Mori Takehiko
Published: March 2004

Alloying in the coordination polymer [Mn1−xCox(tcm)2], (tcm = [C(CN)3]−) has been attempted and the physical properties have been investigated. All compounds are isostructural, but the lattice parameters and the distance between manganese and the adjacent nitrogen atom decrease with increasing cobalt content x. Magnetic susceptibility measurements show a Curie–Weiss behavior, with decreasing Weiss temperature with increasing cobalt content. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis, characterization, and antimicrobial activity of cobalt(II), nickel(II), copper(II) and zinc(II) complexes with ferrocenyl Schiff bases containing a phenol moiety
Authors: Abd‐Elzaher Mokhles M.
Published: March 2004

Three ferrocenyl Schiff bases containing a phenol moiety have been formed by 1:1 molar condensation of acetylferrocene with 2‐aminophenol, 2‐amino‐5‐picoline or 2‐amino‐5‐chlorophenol. These ligands form 2:1 complexs with cobalt(II), copper(II), nickel(II), and zinc(II) ions. From the different spectral data, it was found that coordination of the ligands with the metal ions takes place via the azomethine nitrogen atoms and the deprotonated oxygen of the phenol groups. These ligands and their complexes have been characterized by IR, 1H NMR, 13C NMR, UV–Vis spectra, and elemental analysis. The spectral data of the ligands and their complexes are discussed in connection with the structural changes due to complexation. The complexes prepared showed good antimicrobial activity against Escherichia coli, Bacillus subtilus, and Candida albicans. Copyright © 2004 John Wiley & Sons, Ltd.
Preparation of porous poly(D,L‐lactide) and poly(D,L‐lactide‐co‐glycolide) membranes by a phase inversion process and investigation of their morphological changes as cell culture scaffolds
Authors: Kim So Yeon , Kanamori Toshiyuki , Noumi Yoshiko , Wang Pi‐Chao , Shinbo Toshio
Published: March 2004

Porous membranes composed of the biodegradable polyesters poly(D,L‐lactide) (PLA) and poly(D,L‐lactide‐co‐glycolide) (PLGA) were prepared by a phase inversion process. The molecular weights of the polymers and the concentrations of the polymer solutions affected the pore size and structure of the PLA and PLGA membranes. The molecular weights and morphological changes of the membranes as a function of time were investigated under incubation at 37°C in a humidified 5% CO2 atmosphere. The pores that formed in the membranes changed dramatically with increasing time under these conditions. From the thermal characterization of the polymers in their dry and wet states, we found that the glass‐transition temperatures of PLA and PLGA affected morphological structure changes in the porous membranes. We also prepared a collagen‐coated membrane to improve the interaction between the cell and the substrate, and we observed that the collagen coating enhanced the attachment and growth of Chinese hamster ovary cells on the substrate. Finally, we found that only PLA was a suitable material to prepare a porous membrane scaffold with the phase inversion process with PLA, and a collagen coating was necessary for cell culture on the membrane. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2082–2092, 2004
Alkali–methanol–anthraquinone pulping of Miscanthus x giganteus for thermoplastic composite reinforcement
Authors: Lundquist L. , Arpin G. , Leterrier Y. , Berthold F. , Lindström M. , Månson J.‐A. E.
Published: March 2004

The potential of pulp fiber–reinforced thermoplastics is currently not fully explored in composites. One of the main reasons is that pulp fibers are extracted for the use in papermaking and are thus not optimized for use as reinforcements in thermoplastics. Furthermore, currently used processing methods constitute several severe thermomechanical steps inducing premature degradation of the fibers. A systematic development of these composite materials requires the study of both these aspects. The goal of this work was to optimize fiber extraction against properties relevant to the reinforcement of thermoplastics. To this end, thick‐walled Miscanthus x giganteus pulp fibers were selected. The fibers were pulped by the alkaline–methanol–anthraquinone process. An unreplicated factorial design was applied to determine the effect of key operating variables on fiber thermal stability and mechanical properties. The thermomechanical properties of pulp fibers depend primarily on the morphology and chemical composition of the fiber resource in terms of the respective amounts of lignin, hemicellulose, and cellulose, all strongly influenced by the choice of pulping conditions. Optimal pulping parameters were identified, allowing production of fibers thermally stable up to 255°C with an aspect ratio of 40, a straightness of 95%, and tensile strength as high as 890 MPa. Specific stiffness and strength values with respect to density and material cost of 56 GPa m−3 $−1 and 820 MPa m−3 $−1 were highly competitive with glass fibers, with corresponding values of 15 GPa m−3$−1 and 270–490 MPa m−3 $−1, respectively. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2132–2143, 2004