bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacteremia caused by Achromobacter and Alcaligenes species in 46 patients with cancer (1989–2003)
Authors: Aisenberg Gabriel , Rolston Kenneth V. , Safdar Amar
Published: September 2004

BACKGROUND

Achromobacter and Alcaligenes are emerging infectious gram‐negative bacterial species that can affect immunosuppressed patients. The authors sought to determine the incidence and characteristics of bloodstream infections caused by these organisms in patients with underlying malignancies.

METHODS

All consecutive episodes of hematogenous Achromobacter and Alcaligenes infections recorded from December 26, 1989, to July 27, 2003, were studied retrospectively.

RESULTS

Fifty‐two episodes occurred in 46 patients; 31 patients (67%) had hematologic malignancies, and 24 (52%) experienced neutropenia (< 500 cells/μL). Diabetes mellitus was present in 12 patients (26%), and high‐dose corticosteroids were administered to 12 patients (26%). Seventeen of the 52 infectious episodes (33%) were nosocomial in origin, and 10 patients (22%) had sepsis syndrome. Achromobacter xylosoxidans was the most common cause of infection (47 of 52 episodes [94%]), followed by Ach. denitrificans (2 of 52 episodes [4%]) and Alcaligenes faecalis (1 of 52 episodes [2%]). Twenty‐seven episodes (52%) were polymicrobial, and 3 patients (7%) had concurrent fungemia. Infected intravascular catheters were present in 13 of 52 cases (25%), pneumonia was encountered in 6 of 52 cases (12%), and urinary tract infections were present in 5 of 52 cases (10%). Most isolates exhibited in vitro susceptibility to carbapenems, antipseudomonal penicillins, and trimethoprim‐sulfamethoxazole. Resistance to ciprofloxacin, levofloxacin, aminoglycosides, and monobactam was common. Seven deaths (15%) were attributable to Achromobacter species. Incidence rates for sepsis syndrome, multiorgan dysfunction (Acute Physiology and Chronic Health Evaluation [APACHE] II score > 16), and use of mechanical ventilation and pressor support were significantly higher in patients who died (P < 0.001). Logistic regression analysis revealed that sepsis syndrome and high APACHE II scores were predictors of increased 30‐day mortality.

CONCLUSIONS

Most infections caused by this group of nonfermentative gram‐negative bacteria were attributable to Ach. xylosoxidans, and only one‐third were acquired during hospitalization. The presence of sepsis syndrome has evolved as an independent predictor of poor outcome in patients with high‐risk malignancies accompanied by Achromobacter bloodstream infections. Cancer 2004. © 2004 American Cancer Society.
Parent proxy–reported health‐related quality of life and fatigue in pediatric patients diagnosed with brain tumors and acute lymphoblastic leukemia
Authors: Meeske Kathleen , Katz Ernest R. , Palmer Stephanie N. , Burwinkle Tasha , Varni James W.
Published: September 2004

BACKGROUND

Pediatric patients with brain tumors (BT) are often excluded from health‐related quality of life (HRQOL) studies even though they experience more severe disease and treatment‐related sequelae than children with other types of cancer. Parent proxy assessments of HRQOL allow for greater inclusion of children who are developmentally immature, physically ill, or cognitively impaired.

METHODS

Parents of children ages 2–18 years who were diagnosed at Childrens Hospital Los Angeles and Children's Hospital San Diego with BT (n = 86) or acute lymphoblastic leukemia (ALL; n = 170) evaluated their children's HRQOL over the previous week using the parent‐proxy versions of the Pediatric Quality of Life Inventory (PedsQL™) 4.0 Generic Core scales, the PedsQL™ 3.0 Acute Cancer Module, and the PedsQL™ Multidimensional Fatigue scales. Multiple regression analyses were used to determine the independent effect of the child's diagnosis on HRQOL. Separate analyses were conducted for patients receiving treatment, patients who had not received treatment for < 12 months, and patients who had not received treatment for ≥ 12 months.

RESULTS

Patients with BT exhibited more problems than patients with ALL in the physical, social, psychosocial, school, cognitive, and fatigue domains of HRQOL. The Core Physical Health, Core Psychosocial Health, and Fatigue Total scores for patients with BT demonstrated peak improvements for children who had not received treatment for < 12 months and sharp declines for children who had not received treatment for ≥ 12 months. The Core Physical Health and Fatigue Total scores for patients with ALL were highest (better HRQOL) for those who had not received treatment for ≥ 12 months.

CONCLUSIONS

Pediatric patients and survivors of BT experienced more fatigue and HRQOL problems than patients with ALL, and HRQOL differed by treatment status. Cancer 2004. © 2004 American Cancer Society.
Lymphoepithelial carcinoma versus large cell undifferentiated carcinoma of the major salivary glands
Authors: Wang Cheng‐Ping , Chang Yih‐Leong , Ko Jenq‐Yuh , Lou Pei‐Jen , Yeh Chun‐Fong , Sheen Tzung‐Shiahn
Published: September 2004

BACKGROUND

Undifferentiated carcinomas of the major salivary glands are rare malignant neoplasms of the head and neck region, and patients with these lesions have a poor prognosis. Patients with lymphoepithelial carcinoma (LEC), a specific subtype of undifferentiated carcinoma, however, have a better prognosis, and LEC seems to differ from large cell undifferentiated carcinoma (LCUC) clinically.

METHODS

Sixteen patients with LEC and 12 patients with LCUC were retrieved from the records of 295 patients who had malignancies of the major salivary glands. A retrospective study on clinical manifestations, treatments, long‐term outcomes, and an association with Epstein–Barr virus (EBV) by EBV‐encoded small RNA‐1 in situ hybridization was conducted to identify their differences.

RESULTS

The median patient age was 44.5 years in the LEC group and 56 years in the LCUC group. At the time of presentation, patients with LCUC had a history of rapid‐growing tumor and more advanced locoregional disease (Stage IV in 75% of patients with LCUC compared with 13% of patients with LEC). All 16 patients with LEC underwent curative surgery and radiotherapy, and their 5‐year survival rate was 85.6%. In the LCUC group, only 7 patients were eligible to undergo radical surgery and receive radiotherapy, and their 2‐year survival rate was only 36%. Age > 50 years was associated with a significantly worse prognosis for patients with LCUC. Neck metastasis and tumor size > 6 cm tended to be poor prognostic factors. Tumors were positive for harboring the EBV genome in all 16 LEC samples but in none of the LCUC samples.

CONCLUSIONS

The clinicopathologic features of LEC and LCUC of the major salivary glands were different. LEC was associated with EBV, and patients with LEC had a much better prognosis compared with the prognosis for patients with LCUC. Therefore, LEC should be put in an independent group and should not be included in the same category as undifferentiated carcinomas of the salivary gland. Cancer 2004. © 2004 American Cancer Society.
Contralateral prophylactic mastectomy
Authors: Goldflam Katja , Hunt Kelly K. , Gershenwald Jeffrey E. , Singletary S. Eva , Mirza Nadeem , Kuerer Henry M. , Babiera Gildy V. , Ames Frederick C. , Ross Merrick I. , Feig Barry W. , Sahin Aysegul A. , Arun Banu , Meric‐Bernstam Funda
Published: September 2004

BACKGROUND

Women with unilateral breast carcinoma are at increased risk for developing contralateral breast carcinoma (CBC). The authors sought to identify predictors of malignant or moderate to high‐risk histologic findings in contralateral prophylactic mastectomy (CPM) specimens, and to determine the efficacy of CPM.

METHODS

The authors performed a retrospective review of 239 patients with unilateral early‐stage breast carcinoma who underwent CPM. The number of CBCs expected if the contralateral breast had been left intact was calculated based on CBC rates observed in the Surveillance, Epidemiology, and End Results (SEER) database and on life‐table analysis by family history.

RESULTS

In the current study, 11 patients (4.6%) had occult contralateral malignancies (4 invasive carcinomas and 7 ductal carcinomas in situ) and 44 (18.4%) patients had moderate to high‐risk pathology (8 lobular carcinoma in situ, 11 atypical lobular hyperplasia, 25 atypical ductal hyperplasia). At 1846 patient‐years of follow‐up, only 1 patient (0.4%) developed a new CBC compared with 11 expected cancers based on SEER data. One CBC was observed among 140 patients with a family history of breast carcinoma, compared with 16 expected cancers based on life‐table analysis adjusted for adjuvant therapy. The determinants of significant findings at CPM were invasive lobular histology, estrogen and progesterone receptor positivity, additional ipsilateral moderate to high‐risk pathology, and age > 40 years at cancer diagnosis.

CONCLUSIONS

CPM was associated with a low risk of subsequent development of breast carcinoma. Evaluation of histologic findings in the ipsilateral breast may help to predict the likelihood of significant disease in the contralateral breast and assist in risk stratification. Cancer 2004. © 2004 American Cancer Society.
Can we afford to add chemotherapy to radiotherapy for glioblastoma multiforme? Cost‐identification analysis of concomitant and adjuvant treatment with temozolomide until patient death
Authors: Wasserfallen Jean‐Blaise , Ostermann Sandrine , Pica Alessia , Mirimanoff René‐Olivier , Leyvraz Serge , Villemure Jean‐Guy , Stupp Roger
Published: September 2004

BACKGROUND

Adding temozolomide (TMZ) to standard radiotherapy as a first‐line therapy for glioma may increase costs to a disproportionate degree compared with the resulting survival benefits.

METHODS

Forty‐six consecutive patients (28 males and 18 females; median age, 52 years; age range, 24–70 years) received concomitant TMZ with radiotherapy for 6 weeks followed by adjuvant TMZ for 6 cycles, and they were followed until disease recurrence and then until death. The authors assessed the costs associated with the four phases of treatment from a hospital‐centered perspective.

RESULTS

Treatment was discontinued early in 3 patients, 9 patients, and 15 patients during concomitant TMZ, before adjuvant TMZ, and during adjuvant TMZ, respectively. Karnofsky index values varied between 85% (at the beginning of treatment) and 76% (at the end of treatment). The nature of care after disease recurrence was diverse. Overall survival ranged from 1.4 months to 64.3 months (median, 15.8 months) and was better if surgical debulking could be carried out before treatment. Global costs amounted to €39,092 ± €21,948 (concomitant TMZ, €14,539 ± €4998; adjuvant TMZ, €13,651 ± €4320; follow‐up, €6363 ± €6917; and recurrence, €12,344 ± €18,327), with 53% of these costs being related to the acquisition of TMZ; this represented an eightfold increase in cost compared with radiotherapy alone.

CONCLUSIONS

TMZ may be an effective but costly adjuvant outpatient therapy for patients with glioblastoma multiforme. Definite cost‐effectiveness/utility must be assessed in a randomized Phase III trial. Cancer 2004. © 2004 American Cancer Society.
The controversies surrounding the management of uterine serous carcinoma
Authors: Munkarah Adnan R.
Published: September 2004

Published data confirm the aggressive clinical behavior of uterine serous carcinoma. More research is needed to determine the optimal postoperative management of women diagnosed with this cancer.

See also pages 2214–21.
Distinct migratory behavior of early‐ and late‐born neurons derived from the cortical ventricular zone
Authors: Hatanaka Yumiko , Hisanaga Shin‐Ichi , Heizmann Claus W. , Murakami Fujio
Published: September 2004

Time‐lapse studies indicate that ventricular zone (VZ)‐derived cells show two migratory modes in the cerebral cortex at different stages of mammalian embryogenesis: somal translocation and locomotion. We carried out a systematic analysis to examine whether the migratory behavior of cortical neurons derived from the cortical VZ is stage‐dependent. We labeled VZ cells of mouse embryos with green fluorescent protein (gfp) ‐encoding plasmids by in utero electroporation and evaluated the labeled cells after appropriate survival periods. After electroporation at either embryonic day (E) 12.5 or E15.5, GFP+ VZ cells were initially spindle‐shaped and radially oriented. After leaving the VZ, they transformed into round or horizontally oriented fusiform neurons with many short processes. They then seemed to gradually change into radially oriented bipolar cells as they moved upward. Whereas the earliest emigrants from the VZ labeled at E12.5 (early‐born neurons) reached the top of the cortical plate (CP) after these changes, VZ cells labeled at E15.5 (late‐born neurons) further migrated along the length of radial fibers to reach the top of the CP. A dominant negative form of the gene for cyclin‐dependent kinase 5 (Cdk5DN) was then introduced into VZ cells. Transfection of E12.5 VZ with cdk5dn did not disrupt the migration of the early‐born neurons. However, this caused a failure in migration of the late‐born neurons, although they transformed into bipolar shapes in the intermediate zone. Thus, there appear to be at least two distinct migratory phases of cortical neurons: one common to the early‐ and late‐born neurons, and the other specific to late‐born neurons and Cdk5‐dependent. J. Comp. Neurol. 479:1–14, 2004. © 2004 Wiley‐Liss, Inc.
Quantitative analysis of synaptic distribution along thalamocortical axons in adult mouse barrels
Authors: White Edward L. , Weinfeld Elizabeth , Lev Dmitri L.
Published: September 2004

Quantitative data on thalamocortical synapses in adult mouse barrels have been obtained largely by using lesion‐nduced degeneration to label thalamic afferents. By the time degenerating axons can be identified with the electron microscope, they have broken up into many separate pieces, making it impossible to assess the distribution of synapses along unbroken lengths of afferent. Here, this deficiency is rectified by examining intact lengths of axon labeled by the injection of biotinylated dextran amine into ipsilateral thalamus. Serial thin section reconstructions were analyzed to determine the numbers of synapses per axon length made with dendritic spines vs. shafts and the locations of synapses with respect to axonal varicosities. Results for seven axonal segments from six mice showed an average of 0.2 synapses/μm; 80% were made with spines and 20% with dendritic shafts. Just over two‐thirds of axonal varicosities formed one synapse; most of the remainder formed two and rarely three, whereas 8% formed none. Although most synapses occurred at varicosities (88%), more than 12% were made at cylindrically shaped regions of the reconstructed axonal segments. These results serve as a caveat for the use of light microscopy to quantify synapses, wherein the usual approach is to equate one varicosity with one synapse. For thalamocortical afferents to mouse barrels, equating one varicosity with one synapse would prove to be incorrect more than 30% of the time and would exclude the roughly 12% of synaptic connections made at cylindrical regions of thalamocortical afferents. J. Comp. Neurol. 479:56–69, 2004. © 2004 Wiley‐Liss, Inc.
Neurogranin is expressed by principal cells but not interneurons in the rodent and monkey neocortex and hippocampus
Authors: Singec Ilyas , Knoth Rolf , Ditter Margarethe , Volk Benedikt , Frotscher Michael
Published: September 2004

As a substrate of protein kinase C (PKC), neurogranin (NG) is involved in the regulation of calcium signaling and activity‐dependent plasticity. Recently, we have shown that, in the rodent cerebellum, NG is exclusively expressed by γ‐aminobutyric acidergic Golgi cells, whereas, in the monkey cerebellum, brush cells were the only neuronal population expressing NG (Singec et al. [2003] J. Comp. Neurol. 459:278–289). In the present study, we analyzed the neocortical and hippocampal expression patterns of NG in adult mouse (C57Bl/6), rat (Wistar), and monkey (Cercopithecus aetiops). By using immunocytochemistry and nonradioactive in situ hybridization, we demonstrate strong NG expression by principal cells in different neocortical layers and in the hippocampus by granule cells of the dentate gyrus and pyramidal neurons of CA1–CA3. In contrast, double‐labeling experiments in rodents revealed that neocortical and hippocampal interneurons expressing glutamate decarboxylase 67 (GAD67) were consistently devoid of NG. In addition, by using antibodies against parvalbumin, calbindin, and calretinin, we could demonstrate the absence of NG in interneurons of monkey frontal cortex and hippocampus. Together these findings corroborate the idea of different calcium signaling pathways in excitatory and inhibitory cells that may contribute to different modes of synaptic plasticity in these neurons. J. Comp. Neurol. 479:30–42, 2004. © 2004 Wiley‐Liss, Inc.
Up‐regulation of activated macrophages in response to degeneration in the taste system: Effects of dietary sodium restriction
Authors: McCluskey Lynnette Phillips
Published: September 2004

Dietary sodium restriction combined with unilateral chorda tympani nerve section leads to a rapid and specific decrease in neurophysiological taste responses to sodium in the contralateral, intact chorda tympani (Hill and Phillips [1994] J. Neurosci. 14:2904–2910). Previous work demonstrated that dietary sodium restriction may induce these early functional deficits by inhibiting immune activity after denervation (Phillips and Hill [1996] Am. J. Physiol. 271:R857–R862). However, little is known about the leukocyte response to denervation of taste buds in fungiform papillae. In the current study, it was hypothesized that T cells and macrophages are increased in the tongue after unilateral denervation in control‐fed but not sodium‐restricted animals. Adult, specified pathogen‐free rats received unilateral chorda tympani nerve section or sham section followed by dietary sodium restriction or maintenance on control diet. At day 1, 2, 5, 7, or 50 postsectioning, immunostaining was used to detect the percentage of staining for activated macrophages, the number of αβ T cells, and the number of δγ epithelial T cells in the tongue. The number of lingual T cells did not significantly differ between treatment groups following denervation. However, there was a dramatic bilateral increase in ED1+ staining for activated macrophages in control‐fed rats that peaked at day 2 postsectioning. In contrast, sodium‐restricted rats did not show an increase in activated macrophages above baseline at any time postsectioning. Further analysis of extralingual macrophages indicated that the deficit in immune activity in sodium‐restricted rats is localized to the tongue and is not widespread. A model for immune modulation of taste receptor cell function is proposed based on these novel findings. J. Comp. Neurol. 479:43–55, 2004. © 2004 Wiley‐Liss, Inc.
Regulation of the CREB signaling cascade in the visual cortex by visual experience and neuronal activity
Authors: Suzuki Seigo , Al‐Noori Salwa , Butt Shehzad A. , Pham Tony A.
Published: September 2004

The cAMP‐responsive element (CRE) regulatory pathway has been studied as a model of signal‐regulated transcription and is critical for some forms of learning and adaptation. In cell culture systems, the extracellular‐regulated kinase (ERK) and ribosomal S6 kinase (RSK) couple synaptic signals to CRE‐mediated gene expression by modulating CRE‐binding protein (CREB) phosphorylation. However, it is not known whether sensory experience regulates gene expression in the brain by this mechanism. In this study, we ask: Are activated forms of ERK, RSK, and CREB colocalized in the cortex and are they coordinately regulated by synaptic signals? We find that these three signaling components are regulated in distinct ways. First, cells that show CRE‐lacZ reporter expression, primarily excitatory neurons, do not colocalize with cells containing phospho‐ERK. Second, while phosphorylation of ERK and RSK are modulated by visual experience, phosphorylation of CREB at serines 133, 142, or 143 is detected constitutively and is unaffected by experience. This finding suggests that neural activity might not regulate CREB phosphorylation in vivo. To test this hypothesis, we blocked action potentials by injection of tetrodotoxin and found no effect on CREB phosphorylation. These in vivo data show that, in contrast to cell culture systems, cortical synaptic activity controls CRE‐mediated gene expression without affecting CREB phosphorylation, possibly by modification of RSK and CREB‐associated coregulators. J. Comp. Neurol. 479:70–83, 2004. © 2004 Wiley‐Liss, Inc.
Calcium‐binding protein Caldendrin and CaMKII are localized in spinules of the carp retina
Authors: Schultz Konrad , Janssen‐Bienhold Ulrike , Gundelfinger Eckart D. , Kreutz Michael R. , Weiler Reto
Published: September 2004

Calcium‐binding proteins translate the influx of Ca2+ at excitatory synapses into spatiotemporal signals that regulate a variety of processes underlying synaptic plasticity. In the fish retina, the synaptic connectivity between photoreceptors and horizontal cells undergoes a remarkable plasticity, triggered by the ambient light conditions. With increasing light, the synaptic dendrites of horizontal cells form numerous spinules that are dissolved during dark adaptation. The dynamic regulation of this process is calcium‐dependent and involves the Ca2+/calmodulin‐dependent protein kinase II (CaMKII), but astonishingly its principal regulator Calmodulin (CaM) could not be localized to spinules. Here, we show that antibodies directed against Caldendrin (CaBP1), a member of the EF‐hand calcium‐binding protein family, strongly label the terminal dendrites of horizontal cells invaginating cone pedicles. Double‐labeling experiments revealed that this label is closely associated with label for CaMKII. This association was confirmed at the ultrastructural level. Caldendrin immunoreactivity and CaMKII immunoreactivity are both present in horizontal cell dendrites flanking the synaptic ribbon within the cone pedicle and in particular in spinules formed by these terminals. Comparison of light‐ and dark‐adapted retinas revealed a shift of the membrane‐associated label for Caldendrin from the terminal dendrites into the spinules during light adaptation. These results suggest that Caldendrin is involved in the dynamic regulation of spinules and confirms the assumed potential of Caldendrin as a neural calcium sensor for synaptic plasticity. J. Comp. Neurol. 479:84–93, 2004. © 2004 Wiley‐Liss, Inc.
Expression of GDNF and GFRα1 in mouse taste bud cells
Authors: Takeda Masako , Suzuki Yuko , Obara Nobuko , Uchida Nobuhiko , Kawakoshi Kentaro
Published: September 2004

GDNF (glial cell line‐derived neurotrophic factor) affects the survival and maintenance of central and peripheral neurons. Using an immunocytochemical method, we examined whether the taste bud cells in the circumvallate papillae of normal mice expressed GDNF and its GFRα1 receptor. Using double immunostaining for either of them and NCAM, PGP 9.5, or α‐gustducin, we additionally sought to determine what type of taste bud cells expressed GDNF or GFRα1, because NCAM is reported to be expressed in type‐III cells, PGP 9.5, in type‐III and some type‐II cells, and α‐gustducin, in some type‐II cells. Normal taste bud cells expressed both GDNF and GFRα1. The percentage of GDNF‐immunoreactive cells among all taste bud cells was 31.63%, and that of GFRα1‐immunoreactive cells, 83.21%. Confocal laser scanning microscopic observations after double immunostaining showed that almost none of the GDNF‐immunoreactive cells in the taste buds were reactive with anti‐NCAM or anti‐PGP 9.5 antibody, but could be stained with anti‐α‐gustducin antibody. On the other hand, almost all anti‐PGP 9.5‐ or anti‐α‐gustducin‐immunoreactive cells were positive for GFRα1. Thus, GDNF‐immunoreactive cells did not include type‐III cells, but type‐II cells, which are α‐gustducin‐immunoreactive; on the other hand, GFRα1‐immunoreactive cells included type‐II and ‐III cells, and perhaps type‐I cells. We conclude that GDNF in the type‐II cells may exert trophic actions on type‐I, ‐II, and ‐III taste bud cells by binding to their GFRα1 receptors. J. Comp. Neurol. 479:94–102, 2004. © 2004 Wiley‐Liss, Inc.
Apical‐to‐basal gradients in age‐related cochlear degeneration and their relationship to “primary” loss of cochlear neurons
Authors: Ohlemiller Kevin K. , Gagnon Patricia M.
Published: September 2004

The predominant conceptual framework for understanding human age‐related hearing loss (ARHL, or presbycusis) holds that three different cochlear elements (organ of Corti, afferent neurons, and stria vascularis) can degenerate independently, and exert independent influences on hearing. Within this framework, temporal bones from subjects with ARHL may be classified as exemplifying sensory (referring to organ of Corti), “primary” neural (loss of afferent neurons without loss of their hair cell targets), strial, or mixed ARHL. While there is general agreement as to the types of cochlear cells most affected by aging, there is less agreement about how to classify ARHL, and whether contributions of particular structures to hearing loss can be isolated. The cochlear apex of humans and animals is particularly prone to apparent primary loss of neurons that may represent an aspect of neural ARHL. We recently reported that in 129S6/SvEv mice apical neuronal loss is often accompanied by abnormalities of spiral limbus, pillar cells, and Reissner's membrane (Ohlemiller and Gagnon [2004] J Comp Neurol 469:377–390). We proposed that the initial pathology occurs within limbus, leading to disruption of perilymphatic ion homeostasis, and eventual loss of neurons as one consequence. We have now examined this issue quantitatively in young and old mice of four different strains (129S6/SvEv, CBA/J, C57BL/6, and BALB/c). Abnormalities of apical spiral limbus were found to correlate only weakly with neuronal loss. Strong correlations were found between neuronal loss and abnormalities of both pillar cells and Reissner's membrane, however. Apical neuronal loss and apical‐to‐basal progression of pathology of limbus, pillar cells, and Reissner's membrane run counter to most reported age‐related cochlear trends. Our findings suggest that these changes share a common triggering influence. J. Comp. Neurol. 479:103–116, 2004. © 2004 Wiley‐Liss, Inc.
Unsymmetrically Substituted Dimethyldiaminosilanes as Ligands towards Zirconium(IV)
Authors: Passarelli Vincenzo , Zanella Pierino
Published: September 2004

Unsymmetrically substituted dimethyldiaminosilanes of the general formula SiMe2(NR2)(NR′2) have been prepared by treating LiNR2 with SiMe2Cl(NR′2) (NR2, NR′2 = NMe2, NC4H8, NHiPr, NHtBu, NHCH2CH2NMe2 or NHCH2CH2OMe). Their ligating properties towards zirconium(IV) have been investigated as a function of the nitrogen substituents and the syntheses of the binary compound Zr[SiMe2(NiPr)(NtBu)]2 and of the zirconium derivatives ZrX3(L) [X = Cl, NMe2; L = SiMe(NR)(NR′2), NR = NiPr, NtBu, NCH2CH2NMe2, NCH2CH2OMe; NR′2 = NMe2, NC4H8, NHiPr, NHtBu] are also reported. The solution structures and dynamics of the compounds have been elucidated by 1D/2D multinuclear NMR spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Formation of Sulfur−Sulfur Bonds in Copper Complexes
Authors: Aullón Gabriel , Alvarez Santiago
Published: September 2004

The recently reported dinuclear complexes [Cu2(μ‐S2)(diketiminato)2] that have short S−S distances across their Cu2S2 rings are theoretically studied with the help of density functional calculations and a topological analysis of the electron density. The possibility of obtaining the isomeric form without a S−S bond is explored by comparing the structure and bonding with its oxo analogue. A study of the influence of several terminal‐chelating ligands on the relative stability of the sulfido‐ and the disulfido‐bridged forms is also presented. The only way to stabilize a sulfido‐bridged isomer is found to be via two‐electron reduction, whereas chemical substitutions are not able to produce the cleavage of the S−S bond. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
The Immobilized Porphyrin‐Mediator System Mn(TMePyP)/clay/HBT (clay‐PMS): A Lignin Peroxidase Biomimetic Catalyst in the Oxidation of Lignin and Lignin Model Compounds
Authors: Crestini Claudia , Pastorini Alessandra , Tagliatesta Pietro
Published: September 2004

A biomimetic system for lignin peroxidase (LiP) was designed by using a cationic porphyrin, [Mn(TMePyP)OAc5], supported on the smectitic clay montmorillonite [Mn(TMePyP)/clay]. The natural role of the polypeptidic pocket of LiP was mimicked by the clay. The possibility to use low‐molecular‐weight redox mediators as active readily diffusible oxidizing species has been investigated. This assembly — a sort of “synthetic enzyme” — can be defined as an immobilized porphyrin‐mediator system (clay‐PMS). The clay‐PMS was found to be a stable, recyclable, and efficient catalyst for the environmentally friendly H2O2‐catalyzed oxidation of different lignins and representative lignin model compounds. The clay‐PMS showed a higher reactivity than Mn(TMePyP)/clay alone due to an effective role of the redox mediator on the oxidation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Sources of sulphur in gypsiferous sediments and crusts and pathways of gypsum redistribution in southern Tunisia
Authors: Drake Nick A. , Eckardt Frank D. , White Kevin, H.
Published: September 2004

Southern Tunisia contains one of the most extensive gypsum accumulations in Africa comprising Triassic, Cretaceous, Eocene and Mio‐Pliocene marine evaporites, spring deposits, playa sediments, aeolian sands and gypsum crusts. Sulphur isotope analysis (δ34S) of bedrock samples, groundwater, playa brines, playa sediments, and gypsiferous crusts provides insight into the sources of gypsum in the region and sheds light on the processes that lead to gypsum crust formation. Results suggest that recycling of marine gypsum is the most likely source of the sulphate in the groundwater, playa sediments and crusts. The low δ34S values found in Eocene and Mio‐Pliocene samples suggest that this recycling has been going on for millions of years. Though bedrock appears to be the ultimate source of the gypsum in the crusts, transport of this sulphate to playas, concentration therein, and subsequent dispersal across the landscape by aeolian processes provides the most likely pathway for surﬁcial gypsum crust formation. Comparison of these results with those from Australia, Chile and Namibia suggests that, although the source of the sulphur varies from region to region, the processes of surﬁcial crust formation appear to be similar. Copyright © 2004 John Wiley & Sons, Ltd.
Petrology, geochemistry and environmental significance of silcrete‐calcrete intergrade duricrusts at Kang Pan and Tswaane, central Kalahari, Botswana
Authors: Nash David J. , Mclaren Sue J. , Webb John A.
Published: September 2004

Calcrete–silcrete intergrade duricrusts are an important component of the Kalahari Group sediments of central southern Africa and yet have neither been analysed systematically nor in any detail. In this study, the petrological and geochemical characteristics of suites of calcrete, silcrete and intergrade duricrusts from two fresh, relatively deep exposures at Kang Pan and Tswaane (adjacent to the Okwa Valley) in the central Kalahari, Botswana, are described. The duricrust proﬁle at Kang Pan consists of a highly indurated crystalline non‐pedogenic calcrete which has been extensively siliciﬁed by chalcedony, and, rarely, cryptocrystalline silica or microquartz. Siliciﬁcation is most extensive in lower parts of the proﬁle, where replacement is related to groundwater ﬂuctuations, and in upper sections due to periodic ﬂooding by ephemeral surface water. The exposure at Tswaane consists of a sequence of pale green glauconitic non‐pedogenic silcrete and cal‐silcrete overlain by non‐pedogenic calcrete, all of which have formed within sediments situated upon granitoid‐gneiss bedrock. The siliceous duricrusts are dominated by cryptocrystalline silica cements and appear to have developed through the replacement of a pre‐existing non‐pedogenic calcrete. These siliceous duricrusts have also been calciﬁed at a later date during the formation of the overlying calcrete to produce a complex range of silica–carbonate cements. At both sites, the style and type of siliciﬁcation present appears to be determined by the duration of wetting and the permeability of the precursor calcrete. Geochemical evidence indicates a lack of chemical weathering proﬁle development within the granitoid–gneiss bedrock and considerable differences between the chemical signature of the bedrock and combined duricrusts from Kang and Tswaane. This suggests that bedrock made a minimal contribution in terms of silica and carbonate species to duricrust formation, and that the majority of cementing agents were non‐local. It would therefore appear likely that the geomorphological context of each site had a major inﬂuence upon the development of calcrete, silcrete and intergrade duricrust cements. Copyright © 2004 John Wiley & Sons, Ltd.
Telomere‐mediated mitotic disturbances in immortalized ovarian epithelial cells reproduce chromosomal losses and breakpoints from ovarian carcinoma
Authors: Gisselsson David , Lv Mei , Tsao Sai‐Wha , Man Cornelia , Jin Charlotte , Höglund Mattias , Kwong Yok Lam , Jin Yuesheng
Published: September 2004

Ovarian carcinomas (OCs) often exhibit highly complex cytogenetic changes. Abnormal chromosome segregation at mitosis is one potential mechanism for genomic rearrangements in tumors. In this study, OCs were demonstrated to have dysfunctional short telomeres, anaphase bridging, and multipolar mitoses with supernumerary centrosomes. When normal human ovarian surface epithelial (HOSE) cells were transfected with human papilloma virus 16 e6/e7 genes and subsequently driven into telomere crisis, the same set of mitotic disturbances occurred in a distinct sequence, initiated by telomere dysfunction, followed by anaphase bridging, and then supernumerary centrosomes and multipolar mitoses. The anaphase bridges resolved either by kinetochore‐spindle detachment, corresponding to whole‐chromosome losses in the HOSE karyotypes, or by extensive fragmentation of intercentromeric DNA sequences, corresponding to a high frequency of pericentromeric rearrangements. At later passages, the high degree of instability at telomere crisis was moderated by telomerase expression and centrosome coalescence, ultimately leading to a level of mitotic instability that was highly similar to that in OC cell lines and to complex karyotypes that were similar to those observed in high‐grade OCs. This suggests that a significant proportion of the structural chromosome changes and genomic losses in OC are caused by a specific sequence of mitotic disturbances triggered by telomere crisis. That the model did not produce any of the whole‐chromosome gains observed in OC indicates that these changes develop through a different mechanism. © 2004 Wiley‐Liss, Inc.
Duplication of chromosome arms 9q and 11q: Evidence for a novel, 14q32 translocation–independent pathogenetic pathway in multiple myeloma
Authors: Liebisch Peter , Scheck Daniel , Erné Seiichi Alvise , Wellmann Alexander , Wendl Christiane , Janczik Sibylle , Kolmus Sonja , Kröber Alexander , Einsele Hermann , Straka Christian , Goldschmidt Hartmut , Benner Axel , Stilgenbauer Stephan , Döhner Hartmut
Published: September 2004

14q32 translocations [t(14q)] represent critical but not universal events in multiple myeloma (MM). Gains of chromosome arms 1q, 9q, and 11q (+1q, +9q, and +11q) have recently been identified as frequent aberrations in this disease, but their pathogenetic significance remains unclear. We studied a series of 108 MM patients using fluorescence in situ hybridization and DNA probes mapping to chromosome bands 1q21, 9q34, 11q25, 13q14, and 14q32. Three subsets of tumors were defined: (1) MM+/+ (detection of +9q and +11q; 43.5% of cases), (2) MM+/− (+9q or +11q; 21.3%), and (3) MM−/− (neither +9q nor +11q; 35.2%). The incidence of t(14q) was significantly different in these subgroups: 23% in MM+/+, 56% in MM+/−, and 89% in MM−/−. Deletion of 13q (13q−) also was significantly less frequent in MM+/+ (23%) than in MM+/− and MM−/− (36% and 63%, respectively). The nonrandom distribution of chromosomal aberrations in the present series of MM tumors points to a novel, 14q32 translocation–independent pathogenetic pathway in plasma cell neoplasms. © 2005 Wiley‐Liss, Inc.
Acute lymphoblastic leukemia in a patient with Greig cephalopolysyndactyly and interstitial deletion of chromosome 7 del(7)(p11.2 p14) involving the GLI3 and ZNFN1A1 genes
Authors: Mendoza‐Londono Roberto , Kashork Catherine D. , Shaffer Lisa G. , Krance Robert , Plon Sharon E.
Published: September 2004

Greig cephalopolysyndactyly (GCPS; OMIM 175700) is an autosomal dominant condition caused by mutations of the gene GLI3, located on 7p13. To date, several cases of deletions and/or translocations involving this locus have been reported in patients with GCPS. GLI3 is a transcription factor from the GLI‐Kruppel gene family that has been implicated in three distinct entities: GCPS, Pallister–Hall syndrome, and postaxial polydactyly type A. The zinc finger protein, subfamily 1, member 1 gene (ZNFN1A1; OMIM 603023), on 7p12, codes for a lymphoid‐restricted zinc finger transcription factor, ZNFN1A1, also called IKAROS, that regulates lymphocyte differentiation and has been associated with the development of childhood leukemia. We present the case of a 9‐year‐old Latin‐American boy who was referred for stem cell transplantation because of recurrent acute lymphoblastic leukemia (ALL). On evaluation, he was found to have dysmorphic features consistent with GCPS, including a prominent forehead, down‐slanting palpebral fissures, 1‐2‐3 toe syndactyly, broad thumbs and first toes, and mild developmental delay. He had developed ALL at 5 years of age. Chromosome analysis of bone marrow and fibroblastic cells showed an interstitial deletion of chromosome arm 7p, del(7)(p11.2p14), in 74% and 44% of the cells, respectively. We performed FISH analysis with a BAC clone containing the ZNFN1A1 gene and demonstrated that it is contained in the deleted segment. To our knowledge, this is the first report of a patient with GCPS and leukemia. We hypothesize that constitutional deletion of the ZNFN1A1 gene in this patient may have resulted in an increased risk of lymphoid malignancy. © 2005 Wiley‐Liss, Inc.
Cancer risk according to type and location of ATM mutation in ataxia‐telangiectasia families
Authors: Cavaciuti E. , Laugé A. , Janin N. , Ossian K. , Hall J. , Stoppa‐Lyonnet D. , Andrieu N.
Published: September 2004

Epidemiological studies have indicated that ataxia‐telangiectasia (AT) heterozygotes in AT families have an increased risk of cancer, particularly of breast cancer (BC). However, in BC case–control studies, no significant differences were found in the frequency of ATM mutations between patients and controls. In such studies missense mutations were found more frequently than truncating mutations, suggesting that the cancer risk depends on mutation type. To investigate this possibility, we assessed the risk of BC according to the type and position of the ATM truncating mutation in extended AT families. DNA or RNA that had been isolated from blood or buccal cells of AT children and their relatives was screened for ATM germ‐line mutations using restriction endonuclease fingerprinting, the protein truncation test, fluorescence‐assisted mismatch analysis, and direct sequencing. The standardized incidence ratio of cancer associated with ATM heterozygosity status and type of mutation was estimated. We tested for genotype–phenotype correlations by simulations, permuting mutations among parental branches. No significant difference was found in the relative risk of breast cancer or any other type of cancer based on mutation type. However, the occurrence of BC may be associated with truncating mutations in certain binding domains of the ATM protein (e.g., P53/BRCA1, β‐adaptin, and FAT domains; P = 0.006). In this limited sample set, the presence of missense or truncating ATM mutations was not associated with different cancer risks. The risk of BC appeared to be associated with the alteration of binding domains rather than with the length of the predicted ATM protein. © 2004 Wiley‐Liss, Inc.
Glutamate transport by retinal Müller cells in glutamate/aspartate transporter‐knockout mice
Authors: Sarthy Vijay P. , Pignataro Leonardo , Pannicke Thomas , Weick Michael , Reichenbach Andreas , Harada Takayuki , Tanaka Kohichi , Marc Robert
Published: September 2004

Glutamate transporters are involved in maintaining extracellular glutamate at a low level to ensure a high signal‐to‐noise ratio for glutamatergic neurotransmission and to protect neurons from excitotoxic damage. The mammalian retina is known to express the excitatory amino acid transporters, EAAT1–5; however, their specific role in glutamate homeostasis is poorly understood. To examine the role of the glial glutamate/aspartate transporter (GLAST) in the retina, we have studied glutamate transport by Müller cells in GLAST−/− mice, using biochemical, electrophysiological, and immunocytochemical techniques. Glutamate uptake assays indicated that the Km value for glutamate uptake was similar in wild‐type and GLAST−/− mouse retinas, but the Vmax was ∼50% lower in the mutant. In Na+‐free medium, the Vmax was further reduced by 40%. In patch‐clamp recordings of dissociated Müller cells from GLAST−/− mice, application of 0.1 mM glutamate evoked no current showing that the cells lacked functional electrogenic glutamate transporters. The result also indicated that there was no compensatory upregulation of EAATs in Müller cells. [3H]D‐Aspartate uptake autoradiography, however, showed that Na+‐dependent, high‐affinity transporters account for most of the glutamate uptake by Müller cells, and that Na+‐independent glutamate transport is negligible. Additional experiments showed that the residual glutamate uptake in Müller cells in the GLAST−/− mouse retina is not due to known glutamate transporters—cystine‐glutamate exchanger, ASCT‐1, AGT‐1, or other heteroexchangers. The present study shows that while several known glutamate transporters are expressed by mammalian Müller cells, new Na+‐dependent, high‐affinity glutamate transporters remain to be identified. © 2004 Wiley‐Liss, Inc.
Glial‐mediated neuroprotection: Evidence for the protective role of the NO‐cGMP pathway via neuron–glial communication in the peripheral nervous system
Authors: Thippeswamy Thimmasettappa , Mckay Jennifer S. , Morris Richard , Quinn John , Wong Liang‐Fong , Murphy David
Published: September 2004

The NO‐cGMP pathway has emerged as a neuroprotective signaling system involved in communication between neurons and glia. We have previously shown that axotomy or nerve growth factor (NGF)‐deprivation of dorsal root ganglion (DRG) neurons leads to increased production of NO and at the same time an increase in cGMP production in their satellite glia cells. Blockade of NO or its receptor, the cGMP synthesizing enzyme soluble guanylate cyclase (sGC), results in apoptosis of neurons and glia. We now show that co‐culture of neonatal DRG neurons with either Schwann cells pre‐treated with an NO donor or a membrane‐permeant cGMP analogue; or neurons maintained in the medium from Schwann cell cultures treated in the same way, prevents neuronal apoptosis. Both NO donor and cGMP treatment of Schwann cells results in synthesis of NGF and NT3. Furthermore, if the Schwann cells are previously infected with adenoviral vectors expressing a dominant negative sGC mutant transgene, treatment of these Schwann cells with an NO donor now fails to prevent neuronal apoptosis. Schwann cells treated in this way also fail to express neither cGMP nor neurotrophins. These findings suggest NO‐sGC‐cGMP‐mediated NGF and NT3 synthesis by Schwann cells protect neurons. © 2004 Wiley‐Liss, Inc.
Amino acid transporter SNAT5 localizes to glial cells in the rat brain
Authors: Cubelos Beatriz , González‐González Inmaculada M. , Giménez Cecilio , Zafra Francisco
Published: September 2004

The SNAT5 transporter is a neutral amino acid carrier whose function remains unclear. Structural and mechanistically, SNAT5 is closely related to the SNAT3 transporter that mediates the efflux of glutamine from glial cells and that participates in the glutamate‐glutamine cycle in the brain. In this study, we have analyzed the distribution of SNAT5 in the rat central nervous system using specific antibodies. Through immunoblotting we observed that SNAT5 is ubiquitously but unevenly distributed in the CNS. It accumulates most intensely in the neocortex, the hippocampus, the striatum, and the spinal cord, whereas moderate levels were found in the thalamus, hypothalamus, and brainstem. Light microscopy revealed that the distribution of SNAT5 paralleled that of the vesicular glutamate transporter vGLUT1 in the forebrain regions, whereas in the diencephalon and brainstem, SNAT5 staining was better correlated with that of vGLUT1 and vGLUT2. However, the cellular localization differed from that of the glutamatergic markers, since SNAT5 was expressed exclusively in astrocyte cell bodies and their processes, ensheathing glutamatergic GABAergic and glycinergic terminals. The presence of SNAT5 in astrocyte processes was confirmed by electron microscopy. They were seen not only to surround different neuronal structures, but they were also found in astrocyte endfeet. Taking into consideration the higher levels of SNAT5 in the neighborhood of glutamatergic terminals and the ability of this transporter family to promote the efflux of amino acids from intracellular stores (including glutamine and perhaps glycine), this transporter is likely to be involved in glutamatergic pathways in the brain. © 2004 Wiley‐Liss, Inc.
Role of Na+‐H+ and Na+‐Ca2+ exchange in hypoxia‐related acute astrocyte death
Authors: Bondarenko Alexander , Svichar Nataliya , Chesler Mitchell
Published: September 2004

Cultured astrocytes do not succumb to hypoxia/zero glucose for up to 24 h, yet astrocyte death following injury can occur within 1 h. It was previously demonstrated that astrocyte loss can occur quickly when the gaseous and interstitial ionic changes of transient brain ischemia are simulated: After a 20–40‐min exposure to hypoxic, acidic, ion‐shifted Ringer (HAIR), most cells died within 30 min after return to normal saline (i.e., “reperfusion”). Astrocyte death required external Ca2+ and was blocked by KB‐R7943, an inhibitor of reversed Na+‐Ca2+ exchange, suggesting that injury was triggered by a rise in [Ca2+]i. In the present study, we confirmed the elevation of [Ca2+]i during reperfusion and studied the role of Na+‐Ca2+ and Na+‐H+ exchange in this process. Upon reperfusion, elevation of [Ca2+]i was detectable by Fura‐2 and was blocked by KB‐R7943. The low‐affinity Ca2+ indicator Fura‐FF indicated a mean [Ca2+]i rise to 4.8 ± 0.4 μM. Loading astrocytes with Fura‐2 provided significant protection from injury, presumably due to the high affinity of the dye for Ca2+. Injury was prevented by the Na+‐H+ exchange inhibitors ethyl isopropyl amiloride or HOE‐694, and the rise of [Ca2+]i at the onset of reperfusion was blocked by HOE‐694. Acidic reperfusion media was also protective. These data are consistent with Na+ loading via Na+‐H+ exchange, fostering reversal of Na+‐Ca2+ exchange and cytotoxic elevation of [Ca2+]i. The results indicate that mechanisms involved in pH regulation may play a role in the fate of astrocytes following acute CNS injuries. © 2004 Wiley‐Liss, Inc.