bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal cocaine exposure adversely affects development of the primate cerebral cortex
Authors: Lidow Michael S.
Published: December 2004

This study was conducted to determine whether prenatal exposure to cocaine interferes with the development of the primate cerebral cortex. For this purpose, pregnant rhesus monkeys received cocaine orally (20 mg/kg/day in fruit or candy treats), twice a day from the 40th‐102nd days of pregnancy (E40‐E102), which is a period of corticogenesis in this species. The control group of pregnant animals received fruit or candy treats only. On E64 and E65, all animals received intravenous injections of [3H]thymidine. Monkeys were allowed to deliver at term. The offspring were sacrificed at age 2 months, and their brains were processed for histology and autoradiography. The analysis of cresyl violet‐stained sections showed that prenatal treatment with cocaine significantly altered lamination of the primate cerebral cortex, in some cases completely blending distinction between individual layers. In addition, autoradiographic analysis revealed that in the control animals, [3H]thymidine labeling concentrated in cortical layers V and/or IV depending on the cytoarchitectonic area observed. In contrast, drug‐ treated animals displayed labeled cells in the white matter and cortical layer VI in addition to layers V and IV, suggesting inability of cortical cells to reach proper cortical layers. The number of labeled cells was also much lower in these animals. Finally, immunocytochemical studies with antisera directed toward glial fibrillary acidic protein showed that prenatal exposure to cocaine had dramatic effect on the glial fibers normally observed in the upper cortical layers. In many cortical regions of cocaine‐treated animals, we observed practically no such fibers. This study demonstrates that cocaine administered during pregnancy can significantly affect the development of the primate cerebral cortex. © 1995 Wiley‐Liss, Inc.
Ultrasound antenatal diagnosis of cleft palate by a new technique: the 3D ‘reverse face’ view
Authors: Campbell S. , Lees C. , Moscoso G. , Hall P.
Published: December 2004

Objective

To assess the clinical value of a novel three‐dimensional (3D) ultrasound technique, the reverse face view (3D RF view), in the antenatal categorization of facial clefting and in particular clefting of the hard palate.

Methods

Eight cases of suspected orofacial clefting were examined by 3D surface rendering. The fetal lips and alveolar ridge were examined in the frontal plane and the face was then rotated through 180° on the vertical axis to examine the secondary palate by the 3D RF view.

Results

In each case described, we were able to visualize the fetal face, lips and palate and make an antenatal diagnosis as to whether the palate was affected. In all cases, the antenatal diagnosis was subsequently confirmed. In one case with a left‐sided cleft in the lips and alveolar ridge and an intact hard palate, the correct diagnosis was made but a cleft in the soft palate was missed.

Conclusion

Although clefts of the lips and alveolar ridge are readily diagnosed on high‐quality antenatal ultrasound, visualization of the fetal palate using existing techniques is unreliable. In the patients described here, the 3D RF technique allowed relatively straightforward assessment of the fetal palate with a high degree of accuracy. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Über Silikone, CXX. Organylierungen mit Hilfe von Organotriptychsiloxazolidinen
Authors: Müller R. , Frey H. J.
Published: December 2004

Molekelmassenspektren positiver sowie negativer Ionen stützen die Annahme, daß bei Organotriptych‐siloxazolidinen (Silatranen) zwischen dem Stickstoff und dem dadurch pentacovalenten Silicium eine koordinativ‐covalente Bindung besteht. Mit den Alkyl‐ und Arylverbindungen können Silber‐Alkyle und‐Aryle dargestellt werden, die aber rasch unter Abscheidung von elementarem Silber zerfallen. Die Alkoxyverbindungen ergeben mit Silbernitrat dagegen zunächst Silberoxid. Mit Hilfe der Organo‐triptychsiloxazolidine lassen sich aber beständige Organoquecksilber‐, ‐antimon‐, ‐wismut‐und ‐bleiverbindungen darstellen.
Über Nitrosyl‐Metall‐Komplexe. IX. Kationische und neutrale Derivate des C5H5Mn(CO)2NO+‐Ions
Authors: Brunner H.
Published: December 2004

Bei der Umsetzung von C5H5Mn(CO)2NO+PF mit neutralen Donatoren L entstehen kationische Cyclopentadienyl‐nitrosyl‐mangan‐Derivate:
equation image
. Reine Disubstitutionsprodukte wurden isoliert mit L = Pyridin und 1, 2‐Bis‐(diphenyl‐phosphino)‐äthan; L = Triphenyl‐Phosphin dagegen ergab nur das entsprechende Monosubstitutionsprodukt. Das C5H5Mn(CO)2NO+C+‐Kation reagiert dabei wesentlich schneller als die isoelektronischen Verbindungen C5H5M(CO)2NO der VI. Nebengruppe und C5H5Mn(CO)3.

Das Methylat‐Anion addiert sich sowohl in der monosubstituierten Verbindung C5H5Mn(CO)(NO)P(C6H5)PF als auch im unsubstituierten Komplex C5H5Mn(CO)2NO+PF an den Carbonyl‐Kohlenstoff. Basenadditionen an die NO‐Gruppe im disubstituierten C5H5Mn(NO)(C6H5)2PCH2CH2P(C6H5)PF ließ sich nicht durchführen. Der Nitrosyl‐Stickstoff in NO‐Komplexen ist also dem Angriff von Basen gegenüber wesentlich resistenter als der Carbonyl‐Kohlenstoff in Metall‐Carbonyl‐Verbindungen.
Über Chalkogenocarbonate. XXXVII. Untersuchungen über Dithiocarbamidsäure SC(SH)(NH2) 3. Alkalimetalldithiocarbamate M[SC(S)(NH2)]
Authors: Hahnkamm V. , Kiel G. , Gattow G.
Published: December 2004

Die Dithiocarbamate M[SC(S)(NH2] mit M = K, Rb, Cs, [Φ4As] wurden hergestellt und mit Hilfe chemischer, röntgenographischer und IR‐spektroskopischer Methoden näher untersucht. Die Alkalimetalldithiocarbamate kristallisieren monoklin (pseudorhombisch) mit Z = 8 in der Raumgruppe I2/a–C oder IaC und sind mit der Hochtemperaturmodifikation (β) des NH4[SC(S)(NH2)] isostrukturell. Für diese Verbindungen ist die strukturchemische Volumenregel gut erfüllt.

. Die IR‐Spektren der Dithiocarbamate werden diskutiert.
Untersuchungen in den Systemen MCl2MWO4
Authors: Blechschmidt U. , Möbius R.
Published: December 2004

Durch Auswertung der T‐ und ΔT‐Kurven und der Flächen der Eutektpeaks wurden die Schmelzdiagramme der System Erdalkalimetallchlorid‐Erdalkalimetallwolframat erhalten. Die Systeme sind von einfachem eutektischem Typ. Röntgenuntersuchungen ergaben keine Hinweise über phasenmäßige Veränderungen.
Untersuchungen von mechanisch aktivierten Kontakten. IX. Mechanisch aktivierte Eisenoxide als Konvertierungskantakte für Kohlenmonoxid
Authors: Schrader Richard , Vogelsberger Woleram
Published: December 2004

Durch mechanochemische Reduktion von α‐Fe2O3 in H2‐Atmosphäre wird Magnetit hergestellt, der chargenweise in einer Schwingmühle nachaktiviert wird. Diese Fe3O4‐Proben werden als Kontakte für die CO‐Konvertierung getestet und ihre Festkörpereigenschaften mit verschiedenen Methoden untersucht. Die errechneten Korrelationskoeffizienten gestatten, die katalytische Aktivität mit dem physikalischen Zustand des Festkörpers zu erklären.
Sättigungsdrucke, Bildungsenthalpien von WOCl4und WO2Cl2und das Zersetzungsgleichgewicht 2WO2Cl2= WO3+ WOCl4,g
Authors: Oppermann H.
Published: December 2004

Die Sättigungsdrucke des WOCl4und des WO2CL2und das Zersetzungsgleichgewicht des WO2Cl2wurden im Membrannullmanometer bestimmt und durch Ampullenabschreckversuche ergänzt. Aus der Temperaturabhängigkeit der Sättingungsdrucke wurden die Sublimationsenthalpien und ‐entropienberechnet. Aus der Temperaturabhängigkeit der Gleichgewichtskonstanten erhält man für die Zersetzung des festen WO2Cl2die Reaktionsenthalpie ΔH° (f, 573) = 31,5 (± 0,5) kcal und die Reaktionsentropie ΔS° (f, 573) = 48,7 (± 0,5,) cl. Für die Zersetzung des gasförmigen WO2Cl2erhält manAus den Lösungsenthalpien in 2n NaOH wurden die Bildungsenthalpienberechnet.

Schließlich wurden die Standardentropien zuabgeschätzt.
High Pressure — High Temperature — Synthesis and Properties of Chromium Kyanite, (Al, Cr)2SiO5
Authors: Langer K. , Seifert F.
Published: December 2004

Bei Drücken bis zu 30 kb und Temperaturen von 1000–1500°C konnte in der Al2SiO5‐Modifikation Disthen (Kyanit) Al3+ durch Cr3+ bis zu einer Zusammensetzung (Al1,5Cr0,5)SiO5 substituiert werden. Die Gitterkonstanten ao, bo, co steigen im Verlauf der Substitution an, die triklinen Achsenwinkel α, β, γ bleiben praktisch unverändert. Cr3+ wird in die co‐parallelen Oktaederketten der Struktur eingebaut. Das Remissionsspektrum (240–1000 nm) zeigt außer den erlaubten d–d Übergängen des Cr3+ in oktaedrischer Koordination auch Interkombinationsbanden. Die Halbwertsbreite (∼ 3,8 kK), Lage und Gestalt der 10 Dq‐Bande weist auf eine Symmetrie nicht höher als D4h der Cr3+‐haltigen Oktaeder hin. Dies ist in Übereinstimmung mit der Strukturverfeinerung des reinen Disthens (Burnham 1963).
Schiff base derivatives of titanium(IV) and zirconium(IV)
Authors: Prashar P. , Tandon J. P.
Published: December 2004

The reactions of a few bifunctional and tridentate Schiff bases with titanium‐(IV) and zirconium(IV) isopropoxides in equimolar and bimolar ratios are described. The resulting compounds have been obtained in almost quantitative yields and are of the general formulae M(SB)x(OPri)4−2X (where M = Ti or Zr; SB‐ = anion of the Schiff base SBH2 and x = 1 or 2). Their molecular weights have been determined ebullioscopically and IR spectra recorded.
Darstellung und einige physikalisch‐chemische Eigenschaften des γ ‐FeOOD
Authors: Wolski W. , Burewicz A.
Published: December 2004

Es wurde leichtes und schweres γ‐Eisenhydroxid durch Oxydation von Fe(OH)2 und Fe(OD)2 mit Luftsauerstoff erhalten. Die Darstellung von γ‐FeOOD darf nur in einem sehr begrenzten Intervall der Temperatur, der Fe2+‐Ionenkonzentration und der Zeit des Luftdurchleitens stattfinden. Selbst unter experimentell festgelegten optimalen Versuchsbedingungen sind die Kristallite von γ‐FeOOD nicht so gut ausgebildet wie bei gleich‐hergestelltem γ‐FeOOH.
Reduced cold pressor pain tolerance in non‐recovered whiplash patients: a 1‐year prospective study
Authors: Kasch Helge , Qerama Erisela , Bach Flemming Winther , Jensen Troels Staehelin
Published: December 2004

Whiplash injury and chronic whiplash syndrome represent major health problems in certain western communities, pain being the main symptom. Sensitization of the nociceptive system may play a role for non‐recovery after whiplash injury.

Aims: This study examined if tolerance to endure pain stimuli may predict outcome in whiplash injury.

In a prospective fashion, 141 acute whiplash patients exposed to rear‐end car collision (WAD grade 1–3) and 40 ankle‐injured controls were followed and exposed to a cold pressor test, respectively, 1 week, 1, 3, 6 and 12 months after the injury. VAS score of pain and discomfort was obtained before, during and after immersion of the dominant hand into cold water for 2 min.

The McGill Pain Questionnaire showed that ankle‐injured controls had higher initial pain scores than the corresponding whiplash group, while whiplash‐injured subjects had higher scores at 6 months; pain scores being similar at other time points. No difference was found in cold pressor pain between recovered whiplash patients and ankle‐injured subjects. Non‐recovery was only encountered in whiplash injury. Eleven non‐recovered whiplash patients (defined as: handicap after 1 year) showed reduced time to peak pain from 1 week to 3 months (P < 0.001), 6 months (P < 0.01), but not 12 months after the injury. A larger pain area was seen in non‐recovered vs. recovered whiplash‐injured subjects during the entire observation period (P < 0.001).

Non‐recovery after whiplash was associated with initially reduced cold pressor pain endurance and increased peak pain, suggesting that dysfunction of central pain modulating control systems plays a role in chronic pain after acute whiplash injury.
Program note: applying the UN Process indicators for emergency obstetric care to the United States
Authors: Lobis S. , Fry D. , Paxton A.
Published: December 2004

The United Nations Process Indicators for emergency obstetric care (EmOC) have been used extensively in countries with high maternal mortality ratios (MMR) to assess the availability, utilization and quality of EmOC services. To compare the situation in high MMR countries to that of a low MMR country, data from the United States were used to determine EmOC service availability, utilization and quality. As was expected, the United States was found to have an adequate amount of good‐quality EmOC services that are used by the majority of women with life‐threatening obstetric complications.
Acute reduction of ventricular volume decreases QT interval dispersion in elderly subjects with and without heart failure
Authors: de Carvalho Francine C. , Consolim-Colombo Fernanda M. , Pastore Carlos Alberto , Rubira Marcelo C. , Menegüetti José Claudio , Krieger Eduardo Moacyr , Wajngarten Mauricio
Published: December 2004

To evaluate the effects of acute reduction in ventricular volume (VV) on QT interval dispersion (QTd), 14 men with heart failure (HF; 74.5 ± 2 yr of age) and 11 healthy male control subjects (68 ± 2 yr of age) were studied. For 15 min, lower body negative pressure (LBNP) was applied at −15 and −40 mmHg to reduce venous return. At baseline and during LBNP application, QTd was measured with an 87-lead, body-surface-mapping device; chamber volumes were assessed by radioisotope ventriculography; blood pressure (BP) and heart rate (HR) were continuously monitored; and blood samples were obtained for assessment of norepinephrine (Nor) levels. At −15 mmHg, LNBP application induced a significant decrease in VV but did not change BP and HR in both groups. In addition, Nor levels increased significantly ( P ≤ 0.05) in the control group (from 286.7 ± 31.5 to 388.8 ± 41.2 pg/ml) and in HF patients (from 405.8 ± 56 to 477.6 ± 47 pg/ml), and QTd was significantly ( P ≤ 0.05) decreased in the control group (57.2 ± 3.8 vs. 49.1 ± 3.4 ms) and in HF patients (67.8 ± 6 vs. 63.7 ± 5.9 ms). No additional decreases in VV or QTd were produced by −40 mmHg LNBP, but Nor levels did increase in both groups and reach 475.5 ± 34 and 586.5 ± 60 pg/ml ( P < 0.05) in the control and HF groups, respectively; BP did not change, but HR also increased in both groups. In conclusion, an acute LBNP-induced reduction in VV caused a decrease in the QTd of elderly men regardless of the existence of HF. Because increased sympathetic activity with more intense LBNP was not accompanied by additional changes in QTd, altered QTd may be better related to changes in VV than to autonomic nervous system activity.
Nitrite is an alternative source of NO in vivo
Authors: Tsuchiya Koichiro , Kanematsu Yasuhisa , Yoshizumi Masanori , Ohnishi Hideki , Kirima Kazuyoshi , Izawa Yuki , Shikishima Michiyo , Ishida Tatsuhiro , Kondo Shuji , Kagami Shoji , Takiguchi Yoshiharu , Tamaki Toshiaki
Published: December 2004

In this study, we investigated whether orally administered nitrite is changed to NO and whether nitrite attenuates hypertension in a dose-dependent manner. We utilized a stable isotope of [15N]nitrite (15NO2−) as a source of nitrite to distinguish between endogenous nitrite and that exogenously administered and measured hemoglobin (Hb)-NO as an index of circulating NO in whole blood using electron paramagnetic resonance (EPR) spectroscopy. When 1 mg/kg Na15NO2was orally administered to rats, an apparent EPR signal derived from Hb15NO ( AZ= 23.4 gauss) appeared in the blood. The peak blood HbNO concentration occurred at the first measurement after intake (5 min) for treatment with 1 and 3 mg/kg (HbNO: 4.93 ± 0.52 and 10.58 ± 0.40 μM, respectively) and at 15 min with 10 mg/kg (HbNO: 38.27 ± 9.23 μM). In addition, coadministration of nitrite (100 mg/l drinking water) with Nω-nitro-l-arginine methyl ester (l-NAME; 1 g/l) for 3 wk significantly attenuated the l-NAME-induced hypertension (149 ± 10 mmHg) compared with l-NAME alone (170 ± 13 mmHg). Furthermore, this phenomenon was associated with an increase in circulating HbNO. Our findings clearly indicate that orally ingested nitrite can be an alternative to l-arginine as a source of NO in vivo and may explain, at least in part, the mechanism of the nitrite/nitrate-rich Dietary Approaches to Stop Hypertension diet-induced hypotensive effects.
Fetal origins of adult vascular dysfunction in mice lacking endothelial nitric oxide synthase
Authors: Longo Monica , Jain Venu , Vedernikov Yuri P. , Bukowski Radek , Garfield Robert E. , Hankins Gary D. , Anderson Garland D. , Saade George R.
Published: December 2004

Epidemiological studies have shown increased incidence of hypertension and coronary artery disease in growth-restricted fetuses during their adult life. A novel animal model was used to test the hypothesis regarding the role of an abnormal uterine environment in fetal programming of adult vascular dysfunction. Mice lacking a functional endothelial nitric oxide synthase (NOS3−/−KO, where KO is knockout) and wild-type (WT) mice (NOS3+/+WT) were crossbred to produce homozygous NOS3−/−KO, maternally derived heterozygous (NOS3+/−mat, mother with NOS3 deficiency), paternally derived heterozygous (NOS3+/−pat, normal mother), and NOS3+/+WTlitters. Number of fetuses per litter was smaller in NOS3−/−KOand NOS3+/−matcompared with NOS3+/−patand NOS3+/+WTmice. Adult female mice from these litters (7–8 wk old) were killed, and ring preparations of carotid and mesenteric arteries were mounted in a wire myograph to evaluate the passive and reactive vascular characteristics. Slope of the length-tension plot (a measure of vascular compliance) was increased, and optimal diameter (as calculated by Laplace equation) was decreased in NOS3−/−KOand NOS3+/−matcompared with NOS3+/−patand NOS3+/+WTmice. Acetylcholine caused vasorelaxation in NOS3+/−patand NOS3+/+WTand contraction in NOS3−/−KOand NOS3+/−matmice. Responses to phenylephrine and Ca2+were increased in NOS3−/−KOand NOS3+/−matcompared with NOS3+/−patand NOS3+/+WTmice. Relaxation to isoproterenol was decreased in NOS3−/−KOand NOS3+/−matvs. NOS3+/−patand NOS3+/+WTmice. Abnormalities in the passive and reactive in vitro vascular properties seen in NOS+/−matthat developed in a NOS3-deficient maternal/uterine environment compared with the genetically identical NOS3+/−patmice that developed in a normal environment are the first direct evidence in support of a role for uterine environment in determining vascular function in later life.
Identification of mcl-1 as a BCR/ABL-dependent target in chronic myeloid leukemia (CML): evidence for cooperative antileukemic effects of imatinib and mcl-1 antisense oligonucleotides
Authors: Aichberger Karl J. , Mayerhofer Matthias , Krauth Maria-Theresa , Skvara Hans , Florian Stefan , Sonneck Karoline , Akgul Cahit , Derdak Sophia , Pickl Winfried F. , Wacheck Volker , Selzer Edgar , Monia Brett P. , Moriggl Richard , Valent Peter , Sillaber Christian
Published: December 2004

Antiapoptotic members of the bcl-2 family have recently been implicated in the pathogenesis of chronic myeloid leukemia (CML), a hematopoietic neoplasm associated with the BCR/ABL oncogene. We have examined expression of MCL-1 in primary CML cells and BCR/ABL-transformed cell lines. Independent of the phase of disease, isolated primary CML cells expressed myeloid cell leukemia-1 (mcl-1) mRNA and the MCL-1 protein in a constitutive manner. The BCR/ABL inhibitor imatinib (=STI571) decreased the expression of MCL-1 in these cells. Correspondingly, BCR/ABL enhanced mcl-1 promoter activity, mcl-1 mRNA expression, and the MCL-1 protein in Ba/F3 cells. BCR/ABL-dependent expression of MCL-1 in Ba/F3 cells was counteracted by the mitogen-activated protein-kinase/extracellular signal-regulated kinase (MEK) inhibitor, PD98059, but not by the phosphoinositide 3-kinase inhibitor, LY294002. Identical results were obtained for constitutive expression of MCL-1 in primary CML cells and the CML-derived cell lines K562 and KU812. To investigate the role of MCL-1 as a survival-related target in CML cells, mcl-1 siRNA and mcl-1 antisense oligonucleotides (ASOs) were applied. The resulting down-regulation of MCL-1 was found to be associated with a substantial decrease in viability of K562 cells. Moreover, the mcl-1 ASO was found to synergize with imatinib in producing growth inhibition in these cells. Together, our data identify MCL-1 as a BCR/ABL-dependent survival factor and interesting target in CML. (Blood. 2005;105:3303-3311)
Differences of globin transgene expression in stably transfected cell lines and transgenic mice
Authors: Li Qiliang , Emery David W. , Han Hemei , Sun Jin , Yu Man , Stamatoyannopoulos George
Published: December 2004

Previous studies demonstrated that DNase I hypersensitive site -40 (HS-40) of the α-globin locus is capable of greatly enhancing expression of a hybrid β/γ-globin transcriptional unit in plasmid-transfected murine erythroleukemia (MEL) cells. However, as reported here, this same γ-globin gene expression cassette was only transcribed at trace amounts in erythroid cells of transgenic mice. This lack of expression was not directly attributable to the β/γ-globin transcriptional unit, since this same unit linked to a composite β-globin locus control region was expressed at high levels in transgenic mice. This lack of expression was also not directly attributable to chromosomal position effects, since addition of chromatin insulators failed to increase the frequency of expression. DNase I hypersensitivity and chromatin immunoprecipitation assays demonstrated that the lack of expression was correlated with a closed chromatin structure. We hypothesize that transgenes undergo dynamic changes in chromatin conformation following chromosomal integration and that the discrepant results reported here can be attributed to the relatively high level of chromatin remodeling that occurs in the transgenic mouse model, coupled with the relative inability of the HS-40 element to maintain an open chromatin state under such conditions. (Blood. 2005;105: 3346-3352)
HIF-2α regulates murine hematopoietic development in an erythropoietin-dependent manner
Authors: Scortegagna Marzia , Ding Kan , Zhang Quiyang , Oktay Yavuz , Bennett Michael J. , Bennett Michael , Shelton John M. , Richardson James A. , Moe Orson , Garcia Joseph A.
Published: December 2004

Erythropoiesis in the adult mammal depends critically on erythropoietin, an inducible cytokine with pluripotent effects. Erythropoietin gene expression increases under conditions associated with lowered oxygen content such as anemia and hypoxia. HIF-1α, the founding member of the hypoxia-inducible factor (HIF) alpha class, was identified by its ability to bind and activate the hypoxia-responsive enhancer in the erythropoietin regulatory region in vitro. The existence of multiple HIF alpha members raises the question of which HIF alpha member or members regulates erythropoietin expression in vivo. We previously reported that mice lacking wild-type HIF-2α, encoded by the EPAS1 gene, exhibit pancytopenia. In this study, we have characterized the etiology of this hematopoietic phenotype. Molecular studies of EPAS1-null kidneys reveal dramatically decreased erythropoietin gene expression. EPAS1-null as well as heterozygous mice have impaired renal erythropoietin induction in response to hypoxia. Treatment of EPAS1-null mice with exogenous erythropoietin reverses the hematopoietic and other defects. We propose that HIF-2α is an essential regulator of murine erythropoietin production. Impairments in HIF signaling, involving either HIF-1α or HIF-2α, may play a prominent role in conditions involving altered hematopoietic or erythropoietin homeostasis.
HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and inhibits M-CSF bioactivities
Authors: Suzu Shinya , Harada Hideki , Matsumoto Takahiro , Okada Seiji
Published: December 2004

HIV-1 Nef protein is a major determinant of the pathogenicity of the virus. It has been shown that Nef activates Hck, a member of Src family kinase, in monocytes/macrophages and that the interaction is critical for AIDS-like disease progression in a mouse model. However, it was unclear how the molecular interaction in monocytes/macrophages leads to disease progression. Here, we show for the first time that Nef interferes with the macrophage colony-stimulating factor (M-CSF)/M-CSF receptor signal pathway. In this study, we introduced a conditionally active Nef into myeloid leukemia TF-1-fms cells and analyzed their responsiveness to M-CSF. We found that Nef-activated Hck constitutively associated with the M-CSF receptor complex. The formation of the molecular complex should occur under physiologic conditions, that is, on M-CSF stimulation. Because of aberrant molecular association, the tyrosine-phosphorylation/activation of the receptor in response to M-CSF was markedly diminished in Nef-active cells. Consequently, Nef activation caused the inhibition of M-CSF-mediated proliferation of TF-1-fms cells and macrophage differentiation of the cells induced by M-CSF and 12-O-tetradecanoylphorbol 13-acetate. These results indicate that HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and thereby inhibits M-CSF functions in monocytes/macrophages. (Blood. 2005;105:3230-3237)
FLT3-ITD-TKD dual mutants associated with AML confer resistance to FLT3 PTK inhibitors and cytotoxic agents by overexpression of Bcl-x(L)
Authors: Bagrintseva Ksenia , Geisenhof Stefanie , Kern Ruth , Eichenlaub Sabine , Reindl Carola , Ellwart Joachim W. , Hiddemann Wolfgang , Spiekermann Karsten
Published: December 2004

FLT3 (fms-like tyrosine kinase 3) is constitutively activated in about 30% of patients with acute myeloid leukemia (AML) and represents a disease-specific molecular marker. Although FLT3-LM (length mutation) and TKD (tyrosine kinase domain) mutations have been considered to be mutually exclusive, 1% to 2% of patients carry both mutations. However, the functional and clinical significance of this observation is unclear. We demonstrate that FLT3-ITD-TKD dual mutants induce drug resistance toward PTK inhibitors and cytotoxic agents in in vitro model systems. As molecular mechanisms of resistance, we found that FLT3-ITD-TKD mutants cause hyperactivation of STAT5 (signal transducer and activator of transcription-5), leading to upregulation of Bcl-x(L) and RAD51 and arrest in the G2M phase of the cell cycle. Overexpression of Bcl-x(L) was identified as the critical mediator of drug resistance and recapitulates the PTK inhibitor and daunorubicin-resistant phenotype in FLT3-ITD cells. The combination of rapamycin, a selective mTOR inhibitor, and FLT3 PTK inhibitors restored the drug sensitivity in FLT3 dual mutant–expressing cells. Our data provide the molecular basis for understanding clinical FLT3 PTK inhibitor resistance and point to therapeutical strategies to overcome drug resistance in patients with AML.
The role of CXCL12 in the organ-specific process of artery formation
Authors: Ara Toshiaki , Tokoyoda Koji , Okamoto Rika , Koni Pandelakis A. , Nagasawa Takashi
Published: December 2004

CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor-1 [SDF-1]/pre-B-cell growth-stimulating factor [PBSF]) and its receptor CXCR4 are essential for vascularization in the gastrointestinal tract as well as B lymphopoiesis and colonization of bone marrow by hematopoietic cells. However, the mechanism by which CXCL12/CXCR4 functions in blood vessel formation remains elusive. Here, we have found a novel mode of organ vascularization and determined the roles of CXCL12 in these processes. In the developing small intestine, many short interconnecting vessels form between larger superior mesenteric artery (SMA) and the neighboring primary capillary plexus surrounding the primitive gut, and they elongate and become the arteries supplying the small intestine. Mice lacking CXCL12 or CXCR4 lack the interconnecting vessels but have normal venous networks. The mutants lack filopodial extension and intussusception from endothelial cells of SMAs seen in wild-type embryos. CXCR4 is specifically expressed in arteries in the developing mesenteries and its expression is severely reduced in CXCL12–/– embryos. Mice in which CXCR4 is specifically deleted in the endothelium reveal vascular defects identical to those observed in the conventional CXCR4–/– embryos. Together, CXCL12 acts on arterial endothelial cells of SMA to up-regulate CXCR4 and mediate the connection between the larger artery and neighboring capillary plexus in an organ-specific manner.
Steuerung der ebenen Fahrzeugbewegung mit optimaler Nutzung der Kraftschlusspotentiale aller vier Reifen (Vehicle Dynamics Feedforward Control with Optimal Utilisation of the Adhesion Potentials of all four Tyres)
Authors: Orend Ralf
Published: December 2004

Zur Steuerung der Längs- und Querbewegung eines Fahrzeugs mit Einzelradlenkung, Einzelradbremse, Einzelradantrieb und aktivem Fahrwerk wird eine Strategie entwickelt, mit der sich desssen fahrdynamisches Potential voll ausschöpfen lässt. Die Kräfte an den Rädern werden dabei durch Lösen einer konvexen Optimierungsaufgabe derart betimmt, dass sich alle vier Reifen möglichst weit unterhalb ihrer Krafschlussgrenzen befinden.
Entwicklungsumgebung mit echtzeitfähigen Gesamtfahrzeugmodellen für sicherheitskritische Fahrerassistenzsysteme (Development Environment with Real-time Models for Safety Assistance Systems)
Authors: Schmitt Jürgen , Schorn Matthias , Stählin Ulrich , Isermann Rolf
Published: December 2004

Simulationen gewinnen bei der Funktionsentwicklung für Fahrdynamikregelungen speziell im Stadium der Vorentwicklung immer mehr an Bedeutung. Die Bewertung von Fahrerassistenzsystemen oder Fahrdynamikregelungen ist jedoch aufgrund des subjektiven Fahrgefühls schwierig. Aus diesem Grund wurden ein Force-Feedback-Lenkrad und eine Pedaleinheit mit einem in Fahrversuchen verifizierten echtzeitfähigen Zweispurmodell gekoppelt, die es dem Fahrer ermöglichen, das Gesamtfahrzeugmodell realitätsnah zu steuern. Den aktuellen Fahrzustand erhält der Fahrer über eine 3D-Animation von Fahrzeug und Umgebung in verschiedenen Perspektiven. Mithilfe dieser Entwicklungsumgebung werden neue Ansätze zur Fahrdynamikregelung mit kombiniertem Lenk- und Bremseingriff untersucht.
Systemsicherheit des Active Front Steering (Active Front Steering – System Safety)
Authors: Reinelt Wolfgang , Klier Willy , Reimann Gerd
Published: December 2004

Active Front Steering ist ein elektronisch geregeltes Lenksystem für Kraftfahrzeuge, das situationsabhängig eine Überlagerung eines Winkels zum Lenkradwinkel erlaubt und somit eine Variation der Lenkübersetzung ermöglicht. Für ein solches System muss die funktionale Sicherheit gewährleistet sein. Ziele der funktionalen Sicherheit werden erläutert und messbare Kriterien und deren Nachweisbarkeit dafür diskutiert. Der Analyseprozess, der Sicherheitsintegritätslevel des Systems und der Komponenten bestimmt, wird erläutert, gefolgt von der Spezifikation der Sicherheitsanforderungen und Überwachungsfunktionen. Zum Schluss werden einige modellbasierte Überwachungsfunktionen beschrieben, wie sie im technischen Sicherheitskonzept, speziell in der Verifikation der Eingangssignale des Active Front Steering der Nachfolgegeneration Anwendung finden sollen.
Prüfstandtaugliche Lasermassenspektrometrie von Abgasinhaltsstoffen an Otto- und Dieselmotoren (Laser Mass Spectrometry of Compounds in Exhaust Emissions from Otto and Diesel Engines Adapted for Use at Motor Test Facilities)
Authors: Boesl Ulrich , Weishäupl Ronald , Püffel Peter , Thiel Wolfgang
Published: December 2004

Die Lasermassenspektrometrie zum simultanen Nachweis von Stickoxiden, Ammoniak und anderer Abgaskomponenten (N2O, CO, O2, H2O, Aromaten) wird vorgestellt. Am Motorprüfstand wurden ausführliche Messserien an Otto- und Dieselmotoren vor und nach Katalysatoren, im Zylinder und im Vergleich mit konventionellen Methoden durchgeführt.
Coupling of an induced fit enzyme to polydiacetylene thin films: Colorimetric detection of glucose
Authors: Cheng Quan , Stevens Raymond C.
Published: December 2004

A new biosensor design is demonstrated, in which a protein conformational change is used as a trigger mechanism for a low‐cost, solid‐state sensor (see also the cover). The figure illustrates the principle: an enzyme (hexokinase, large white shape) immobilized on a lipid polydiacetylene (PDA) layer undergoes a conformational change when glucose (dark shape) binds to it. The resulting stress in the PDA layer produces a color change.

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Conformational polymorphism of oligothiophenes: X‐ray structure of the monoclinic form of 3, 3′, 4″, 3″′‐Tetrakis(methylsulfany‐l)2, 2′:5′, 2″:5″, 2″′‐Quaterthiophene
Authors: Barbarella Giovanna , Zambianchi Massimo , del Fresno I Marimon Montserrat , Antolini Luciano , Bongini Alessandro
Published: December 2004

Conformational polymorphism of an oligothiophene the title compound (T4S), is reported for the first time. Efficient synthesis of T4S produced, in addition to the triclinic, deep orange crystals reported previously, a second (yellow, monoclinic) form of T4S, whose structure as revealed by single‐crystal X‐ray diffraction is presented here. The synthetic pathway is outlined and the molecular structure and crystal packing are discussed. The significantly different π‐delocalization in the two conformations indicates the need for very careful molecular characterization.
Chemical vapor deposition of thin polymer films used in polymer‐based light emitting diodes
Authors: Vaeth Kathleen M. , Jensen Klavs F.
Published: December 2004

A chemical vapor deposition (CVD) technique for the preparation of the conjugated polymer PPV, poly(phenylenevinylene), is presented. The thin films were prepared by CVD of a chlorine precursor polymer from a dichloro‐p‐xylene monomer followed by a thermal conversion step. The preparation and apparatus are detailed and results of UV‐vis and IR spectroscopy discussed. Spontaneous orientation of the polymer during growth is revealed, which suggests the possibility of fabricating chain‐oriented polymers by CVD.
Interfaces and interphases of (bio)materials: Definitions, structures, and dynamics
Authors: Geckeler Kurt E. , Rupp Frank , Geis‐Gerstorfer Jürgen
Published: December 2004

What exactly is an interface, and when is an interphase the more correct concept? The nature of interfaces and the phenomena occurring there are described before the role of interphases is illustrated with a series of examples taken from purely artificial systems (e.g., polymer and polymer‐metal “interfaces”) and natural and mixed artificial–natural systems (e.g., the multilayer interphase of a biomedical system such as a dental implant). The approach presented demonstrates that “interphase” or “interface” depends to some extent on the point of view.
A prospective study of nontraumatic coma: Methods and results in 310 patients
Authors: Bates D. , Caronna J. J. , Cartlidge N. E. F. , Knill‐Jones R. P. , Levy D. E. , Shaw D. A. , Plum F.
Published: December 2004

Neurological signs and outcome are compared in the first 310 patients from a continuing prospective study of coma not caused by trauma or drugs. Sixteen percent of the patients achieved an independent existence within a month; severe disability or the vegetative state developed in 25% of patients comatose for six hours and in 79% of those still in coma after a week. The chance of regaining an independent existence was greater in patients who, by one day, obeyed commands or moved the limbs appropriately in response to noxious stimuli or who had attained any of the following: orienting eye movements, normal responses to oclulocephalic or ocluovestibular stimulation, or normal muscle tone. Conversely, the chance of regaining an independent existence fell in patients who, after one day, had either extensor responses of the limbs or failed to move them in response to noxious stimuli or who lacked eye opening, pupillary reactions, corneal responses, or any eye movement in response to oculovestibular or oculocephalic stimulation. Beyond these general guidelines, numbers of patients with particular signs are presently too small for confident prediction of outcome.
Pharmacological prophylaxis against the development of kindled amygdaloid seizures
Authors: Turner Ira M. , Newman Stephen M. , Louis Sydney , Kutt Henn
Published: December 2004

The kindling of amygdaloid and cortical seizures in cats was used to study the prophylactic effects of phenobarbital, phenytoin, ethosuximide, acetazolamide, and dexamethasone. Phenobarbital prevented the evolution of such seizures beyond stage 4 in all amygdaloid‐kindling animals during 160 days of study. The prophylactic effect persisted on periodic challenge after the drug had been discontinued. Phenytoin, ethousuximide, acetazolamide, and dexamethasone appeared to have no prophylactic effect against the development of kindled amygdaloid seizures. With cortical kindling, both phenobarbital and phenytoin retarded the evolution of seizures without achieving true prophylaxis. The drugs appeared to act as suppressants. Prophylaxis was not an “all‐or‐none” phenomenon but rather a limitation of the stage of seizure evolution.
The relationship between parkinson syndrome and vascular siderosis: An electron microprobe study
Authors: Duckett Serge , Galle Pierre , Kradin Richard
Published: December 2004

Vascular siderosis (VS) refers to the presence of mineralized small and medium‐sized arteries in the globus pallidus, usually regarded as reflecting an aging process. The electron probe analysis of deposits in vascular siderosis in 10 patients dying of parkinsonism and in 8 other patients without parkinsonism is reported here. The microprobes identified a total of 11 elements in the VS in these 18 patients. Five elements—lead, aluminum, sulfur, manganese, and barium—were present only in VS associated with parkinsonism. Statistically, the association of lead was highly significant while that of aluminium and sulfur was only suggestive. Lead was present in 7 of the 10 patients with parkinsonism and aluminium and sufur in 4. The significance of the presence of sulfur is difficult to assess since its compounds are normally present in large quantities in the brain. These findings raise the question whether lead and aluminum may be associated in some way with the pathogenesis of certain forms of Parkinson disease.
Pedigree testing in duchenne muscular dystrophy
Authors: Roses A. D. , Roses M. J. , Metcalf B. S. , Hull K. L. , Nicholson G. A. , Hartwig G. B. , Roe C. R.
Published: December 2004

Female relatives of 41 Duchenne muscular dystrophy proband cases were studied with a panel of carrier‐detection tests. A total of 277 relatives were tested in order to determine which mothers had affected sons as a result of new mutation. In 39 of 41 pedigrees the data demonstrate that a mutation cannot be postulated; the 2 negative pedigrees were inadequately tested. Our data suggest that all mothers of affected sons should be considered genetic carriers (heterozygotes) until proved otherwise. Our findings also raise questions concerning what mechanisms skew the indirect statistical estimates of mutation that are in common use.
Familial paroxysmal dystonic choreoathetosis and its differentiation from related syndromes
Authors: Lance James W.
Published: December 2004

Four generations of a family are described in which 7 of 8 affected members suffered from prolonged dystonic seizures; the eighth member's attacks were those of paroxysmal choreoathetosis. The attacks lasted up to 4 hours, were precipitated by alcohol, emotion, or fatigue, and responded poorly to phenytoin and barbiturates but were controlled by clonazepam. Autopsy on an affected child who died a “crib death” at the age of 2 years disclosed no major abnormality of the brain. This family appears to have the same condition as that described by Mount and Reback in 1940, Forssman in 1961, and Richards and Barnett in 1968, which the last authors termed paroxysmal dystonic choreoathetosis to distinguish it from the more common movement‐induced (kinesigenic) form of the disorder.

Analysis of reports of 100 cases of paroxysmal kinesigenic choreoathetosis shows that the attacks last less than 5 minutes, are precipitated by sudden movement or startle, and usually respond well to phenytoin or barbiturates. A clinical classification is presented in which the kinesigenic form is divided into a familial group (72% of cases) and a sporadic group (28% of cases) and contrasted with paroxysmal dystonic choreoathetosis. One family with an intermediate form, in which dystonic choreoathetosis was provoked by continued exertion and lasted for up to 30 minutes, is also reported.
Programmed feeding as a model of chronic alcoholism in the rat
Authors: Craig J. R. , Munsat T. L. , Chuang M.
Published: December 2004

Programmed‐feeding polydipsia results in a reliable model of chronic alcoholism in the rat. High oral ethanol consumption and a predictable withdrawal reaction associated with audiogenic seizures are produced. The maintenance of high blood ethanol levels for three weeks in 18 male Charles River rats was associated with audiogenic seizures after 6 to 8 hours of withdrawal. These chronic alcoholic rats had enhanced blood clearance of ethanol. The cerebral cortical crude mitochondrial function showed a decrease in total and magnesium‐dependent adenosine triphosphatase activity in alcoholic and control (water‐fed) rats compared with normal rats.
Acute measles encephalitis of the delayed type
Authors: Lyon Gilles , Ponsot Gérard , Lebon Pierre
Published: December 2004

An acute measles encephalitis with epilepsia partialis continua occurred three months after measles in a previously healthy child with no detectable immunological defect. Levels of measles antibodies in serum and cerebrospinal fluid were high, and tubular inclusions of the type seen in subacute sclerosing panencephalitis were found in nerve cell nuclei. A communicating high‐pressure hydrocephalus developed in the later stage of the disease. This case demonstrates that measles encephalitis of the delayed type should systematically be considered in children with acute encephalitis.
Cysticercosis of the nervous system: Diagnosis by means of specific radioimmunoscan
Authors: Skromne‐Kadlubik Gregorio , Celis Cesar , Ferez Antonio
Published: December 2004

A new method for diagnosing cerebral cysticercosis by means of specific radioimmunoscan is described. The method has been evaluated in 24 patients with encouraging results. The technique involves a single intravenous injection followed by brain scanning and thus far has been entirely nontoxic. The accuracy of the scan was confirmed in 6 patients by surgical removal of lesions that coincided in location and number with the diagnostic scan of the parasites.
Tissue culture studies of demyelinating disease: A critical review
Authors: Seil Fredrick J.
Published: December 2004

Tissue culture studies of human and experimental demyelinating diseases have demonstrated that sera from patients with multiple sclerosis reversibly demyelinate central nervous system cultures. Similar changes are evoked by sera from animals with experimental allergic encephalomyelitis induced by inoculation with whole central nervous system tissue but not by encephalitogenic myelin basic protein. Sera and buffy coat or lymph node cells from humans with idiopathic polyneuritis and animals with experimental allergic neuritis demyelinate cultures of peripheral nervous system tissue.

While these studies have contributed to speculations about pathogenetic mechanisms of demyelinating diseases, including the role of both circulating antibodies and delayed hypersensitivity factors, a number of important questions remain unanswered. Among these are the identity of the antigens that evoke antimyelin antibodies and the precise relationship of serum or cellular antimyelin factors to the pathogenesis or clinical course of the demyelinating diseases. Further studies with this technique may provide more complete information about the role of immunological events in induction of disease.
Growth rates of epidermoid tumors
Authors: Alvord Ellsworth C.
Published: December 2004

Consideration of the most likely method of growth of epidermoid tumors, either congenital or traumatic in origin, suggests that they grow linerarly, at rates approximating those reported for normal human skin, rather than exponentially, as most tumors do. Such a linear rate of growth would be expected of tumors derived from a single layer of basal germinal cells spread out over a surface area.
Tonic pupils with acute ophthalmoplegic polyneuritis
Authors: Keane James R.
Published: December 2004

Two patients with the symmetrical ophthalmoplegic varient of acute idopathic polyneuritis (Fisher's syndrome) developed bilateral dilated pupils with cholinergic supersensitivity and light‐near dissociation (tonic pupils), indicating involvement of the postganglionic parasympathetic neuron within the orbit. Supranuclear eye movement dysfunction also was present, indicated by relative levator sparing in both patients and by preservation of Bell's phenomenon in 1 patient despite paralysis of voluntary upward gaze.

The lesions that produce the eye signs of ophthalmoplegic polyneuritis are not necessarily restricted to the cranial nerve trunks. The present cases support a relationship between the ophthalmoplegic variant of the Guillain‐Barré syndrome and acute postifectius encephalomyelitis (brainstem encephalitis) on the one hand, and idiopathic autonomic neuropathies such as the Holmes‐Adie syndrome and pandysautonomia on the other.
The ocular motor defects in progressive supranuclear palsy
Authors: Troost B. Todd , Daroff Robert B.
Published: December 2004

The results of quantitative infrared horizontal eye movement recordings in 8 patients with progressive supranuclear palsy are presented. Some of the patients had total paralysis of vertical movements, but none had completely lost the ability to perform horizontal eye movements.

All patients had a defect in ocular fixation previously undescribed in this condition: the universal presence of square‐wave jerks. Analysis of refixation sacades demonstrated hypometria, slow velocity/amplitude relationships, and profound prolongation of duration. The pursuit abnormality, characterized clinically by “cogwheel” eye movements, represented the inability to match eye velocity to target velocity. The ratio of peak eye velocity to peak target velocity (pursuit gain) was 0.2 to 0.5. Defects in the vestibuloocular reflex included inability to increase the gain of the reflex (ratio of peak eye velocity to head velocity) during viewing of a visible, stationary target and failure to suppress the reflex when viewing a target rotating with the head.
WAIS performance in brain‐damaged left‐ and right‐handers
Authors: Todd John , Satz Paul
Published: December 2004

WAIS performance was compared in 35 pairs of left‐ and right‐handed subjects who had been individually matched for lateralization, cause of brain damage, age, education, and gender. WAIS results were similar in the two groups as well as in two subgroups of subjects with unilateral brain damage. No differences between the unilateral groups were found to support the hypothesis advanced by Levy and Nagylaki in 1972 that left‐handers have inferior visual‐spatial abilities.
Phenytoin‐Related cerebellar degeneration without seizures
Authors: Rapport Richard L. , Shaw Cheng‐Mei
Published: December 2004

Cerebellar changes have been reported in relationship to epilepsy alone as well as to phenytoin therapy for the control of seizures. The cliniconeuropathological correlation between these changes and epilepsy or the anticonvulsant is usually complicated by the presence of both variables. Experimental evidence suggests that phenytoin alone may be sufficient to cause cerebellar changes following intoxication. We report a case of cerebellar degeneration in a patient treated with isoniazid and prophylactically treated with phenytoin who never had a seizure.
Persistent cerebellar ataxia after exposure to toluene
Authors: Boor John William , Hurtig Howard I.
Published: December 2004

An optometrist and a glue sniffer exposed independently to toluene vapors developed cerebellar, pyramidal, and cognitive dysfunction. All deficits cleared completely in the former but persisted in the latter. The findings confirm a previous report of a toluene‐induced neurological syndrome that is exclusively central, sparing peripheral nerves.