bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired arachidonic acid-mediated dilation of small mesenteric arteries in Zucker diabetic fatty rats
Authors: Zhou Wei , Wang Xiao-Li , Kaduce Terry L. , Spector Arthur A. , Lee Hon-Chi
Published: December 2004

Arachidonic acid (AA) is a precursor of important vasoactive metabolites, but the role of AA-mediated vasodilation in Type 2 diabetes is not known. Using Zucker diabetic fatty (ZDF) rats, we examined the effects of AA in small mesenteric arteries preconstricted with endothelin. In ZDF rat mesenteric arteries, 1 μM AA produced only one-third the amount of dilation as in vessels from lean control animals. In lean control rats, the effect of AA was significantly and predominantly inhibited by the lipoxygenase inhibitors baicalein and cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC). However, baicalein and CDC had no effect on AA-mediated dilation in ZDF rat mesenteric arteries. The major [3H]AA metabolite produced by isolated mesenteric arteries in both lean and ZDF rats was 12-hydroxyeicosatetraenoic acid (12-HETE), but the amount of [3H]12-HETE produced by ZDF rat vessels was only 36% of that of control vessels. In addition, 12-HETE produced similar amounts of dilation in lean and ZDF rat mesenteric arteries. Immunoblot analysis showed an 81% reduction in 12-lipoxygenase protein in ZDF rat mesenteric arteries. Immunofluorescence labeling showed strong nitrotyrosine signals in ZDF rat mesenteric arteries that colocalized with 12-lipoxygenase in endothelium, and 12-lipoxygenase coprecipitation with anti-nitrotyrosine antibodies was enhanced in ZDF rat vessels. We conclude that AA-mediated relaxation in ZDF rat small mesenteric arteries is impaired due to reduced 12-lipoxygenase protein and activity. Increased oxidative stress and nitration of 12-lipoxygenase may underlie the impairment of AA-mediated relaxation in small mesenteric arteries of diabetic rats.
PGE2-induced hypertrophy of cardiac myocytes involves EP4 receptor-dependent activation of p42/44 MAPK and EGFR transactivation
Authors: Mendez Mariela , LaPointe Margot C.
Published: December 2004

Upon induction of cyclooxygenase-2 (COX-2), neonatal ventricular myocytes (VMs) mainly synthesize prostaglandin E2 (PGE2). The biological effects of PGE2 are mediated through four different G protein-coupled receptor (GPCR) subtypes (EP1–4). We have previously shown that PGE2 stimulates cAMP production and induces hypertrophy of VMs. Because the EP4 receptor is coupled to adenylate cyclase and increases in cAMP, we hypothesized that PGE2 induces hypertrophic growth of cardiac myocytes through a signaling cascade that involves EP4-cAMP and activation of protein kinase A (PKA). To test this, we used primary cultures of VMs and measured [3H]leucine incorporation into total protein. An EP4 antagonist was able to partially block PGE2 induction of protein synthesis and prevent PGE2-dependent increases in cell surface area and activity of the atrial natriuretic factor promoter, which are two other indicators of hypertrophic growth. Surprisingly, a PKA inhibitor had no effect. In other cell types, G protein-coupled receptor activation has been shown to transactivate the epidermal growth factor receptor (EGFR) and result in p42/44 mitogen-activated protein kinase (MAPK) activation and cell growth. Immunoprecipitation of myocyte lysates demonstrated that the EGFR was rapidly phosphorylated by PGE2 in VMs, and the EP4 antagonist blocked this. In addition, the selective EGFR inhibitor AG-1478 completely blocked PGE2-induced protein synthesis. We also found that PGE2 rapidly phosphorylated p42/44 MAPK, which was inhibited by the EP4 antagonist and by AG-1478. Finally, the p42/44 MAPK inhibitor PD-98053 (25 μmol/l) blocked PGE2-induced protein synthesis. Altogether, we believe these are the first data to suggest that PGE2 induces protein synthesis in cardiac myocytes in part via activation of the EP4 receptor and subsequent activation of p42/44 MAPK. Activation of p42/44 MAPK is independent of the common cAMP-PKA pathway and involves EP4-dependent transactivation of EGFR.
Norepinephrine induces endoplasmic reticulum stress and downregulation of norepinephrine transporter density in PC12 cells via oxidative stress
Authors: Mao Weike , Iwai Chikao , Qin Fuzhong , Liang Chang-seng
Published: December 2004

Cardiac norepinephrine (NE) uptake is reduced in cardiomyopathy. This change is associated with a decrease of NE transporter (NET) receptor and can be reproduced in PC12 cells by extracellular NE. To study whether this effect of NE is mediated via impaired glycosylation and trafficking of NET in the endoplasmic reticulum (ER), we measured the distribution of glycosylated 80-kDa NET and unglycosylated 46-kDa NET in the membrane and cytosolic fractions of PC12 cells. We found that NE decreased glycosylated NET in both membrane and cytosolic fractions and increased cytosolic unglycosylated NET protein. Similar results were produced by tunicamycin and thapsigargin, two agents that induce ER stress by inhibiting N-glycosylation of membrane proteins and disrupting calcium homeostasis, respectively. Also, like the ER stressors, NE not only increased phosphorylation of both the α-subunit of eukaryotic initiation factor-2 and its upstream RNA-dependent protein kinase-like ER kinase over 12 h of treatment but also increased ER chaperone molecule glucose-regulated protein 78 and the nuclear transcription factor C/EBP homologous protein. Antioxidants superoxide dismutase and catalase prevented the downregulation of NET proteins and induction of ER stress signals produced by NE but not by tunicamycin or thapsigargin. The results indicate that the downregulation of membrane NET by NE is mediated by decreased N-glycosylation of NET proteins secondary to induction of ER stress pathways by NE-derived oxidative metabolites. Interventions involving the ER stress pathways may provide novel therapeutic strategies for the treatment of sympathetic dysfunction in heart failure.
Inhibition of chloride secretion in human bronchial epithelial cells by cigarette smoke extract
Authors: Kreindler James L. , Jackson Alan D. , Kemp Philip A. , Bridges Robert J. , Danahay Henry
Published: December 2004

Chronic bronchitis, a disease mainly of cigarette smokers, shares many clinical features with cystic fibrosis, a disease of altered ion transport, suggesting that the negative effects of cigarette smoke on mucociliary clearance may be mediated through alterations in ion transport. We tested the hypothesis that cigarette smoke extract would inhibit chloride secretion in human bronchial epithelial cells. In agreement with studies in canine trachea, cigarette smoke extract inhibited net chloride secretion without affecting sodium transport. We performed microelectrode impalements and impedance analysis studies to investigate the physiological mechanisms of this inhibition. These data demonstrated that cigarette smoke extract caused an acute increase in membrane resistances in conjunction with apical membrane hyperpolarization, an effect consistent with inhibition of an apical membrane anion conductance. After this acute phase, both membrane resistances decreased while membrane potentials continued to hyperpolarize, indicating that cigarette smoke extract also inhibited the basolateral entry of chloride into the cell. Furthermore, cigarette smoke extract caused an increase in mucin secretion. Therefore, the ion transport phenotype of human bronchial epithelial cells exposed to cigarette smoke extract is similar to that of cystic fibrosis epithelia in which there is sodium absorption out of proportion to chloride secretion in the setting of increased mucus secretion.
Equimolar doses of atrial and brain natriuretic peptides and urodilatin have differential renal actions in overt experimental heart failure
Authors: Chen Horng H. , Cataliotti Alessandro , Schirger John A. , Martin Fernando L. , Burnett John C.
Published: December 2004

A hallmark of overt congestive heart failure (CHF) is attenuated cGMP production by endogenous atrial natriuretic peptide (ANP) with renal resistance to ANP. ANP and brain natriuretic peptides (BNP) are of myocardial origin, whereas urodilatin (Uro) is thought to be derived from kidney. All three peptides are agonists to the natriuretic peptide-A receptor. Our objective was to compare the cardiorenal and humoral actions of ANP, BNP, and Uro in experimental overt CHF. We determined cardiorenal and humoral actions of 90 min of intravenous equimolar infusion of ANP, BNP, and Uro (2 and 10 pmol·kg−1·min−1) in three separate groups of anesthetized dogs with rapid ventricular pacing-induced overt CHF (240 beats/min for 10 days). BNP resulted in increases in urinary sodium excretion (UNaV) (2.2 ± 0.7 to 164 ± 76 μeq/min, P < 0.05) and glomerular filtration rate (GFR) (27 ± 4 to 52 ± 11 ml/min, P < 0.05) that were greater than those with Uro ( P < 0.05), whereas ANP did not result in increases in UNaV or GFR. Increases in plasma cGMP (25 ± 2 to 38 ± 2 pmol/ml, P < 0.05) and urinary cGMP excretion with BNP (1,618 ± 151 to 6,124 ± 995 pmol/min, P < 0.05) were similar to those with Uro; however, there was no change with ANP. Cardiac filling pressures were reduced in all three groups. These studies also support the conclusion that in experimental overt CHF, renal resistance to natriuretic peptides in increasing rank order is BNP < Uro < ANP.
A naturally occurring E30Q mutation in the Gla domain of protein Z causes its impaired secretion and subsequent deficiency
Authors: Souri Masayoshi , Koseki-Kuno Shiori , Iwata Hiroki , Kemkes-Matthes Bettina , Ichinose Akitada
Published: December 2004

Protein Z is a vitamin K–dependent glycoprotein that plays a role in the regulation of coagulation. A nucleotide substitution of G by C in exon II of the protein Z gene, resulting in the replacement of Glu-30 with Gln (E30Q), and a G to A transition at the 79th nucleotide in intron F (IntF79G/A) were heterozygously identified in a patient with a severe thrombotic tendency, whose plasma protein Z level was about 15% of normal. Other vitamin K–dependent coagulation factors were within normal ranges. Glu-30 is one of 13 γ-carboxylation sites in protein Z and is well conserved among vitamin K–dependent proteins. Expression studies revealed that the E30Q mutant was not released from synthesizing cells, although wild-type protein Z was readily secreted in a vitamin K–dependent fashion. The E30Q mutant was N-glycosylated, γ-carboxylated, and translocated from the endoplasmic reticulum (ER) to the Golgi in the presence of vitamin K, as was the wild type. Coexpression of E30Q with wild-type protein Z interfered with the secretion of the wild type, while only a minor or no effect was observed on the secretion of factor X and plasminogen. The IntF79A allele has been reported to be also associated with lowered protein Z levels.
Iron regulates T-lymphocyte sensitivity to the IFN-γ/STAT1 signaling pathway in vitro and in vivo
Authors: Regis Gabriella , Bosticardo Marita , Conti Laura , De Angelis Stefania , Boselli Daniela , Tomaino Barbara , Bernabei Paola , Giovarelli Mirella , Novelli Francesco
Published: December 2004

The refractoriness of T cells to the interferon-γ (IFN-γ)/signal transducer and activator of transcription 1 (STAT1) pathway, which shields them from the antiproliferative effect of IFN-γ, is attributed mainly to down-regulation of the IFN-γR2 signaling chain. However, the mechanisms responsible for this down-regulation are unclear. Here we show that iron uptake mediated by the transferrin receptor (TfR) delivers a signal that leads to IFN-γR2 internalization and thus plays an essential role in attenuating activation of the IFN-γ/STAT1 pathway in human T lymphocytes. The effect of iron on IFN-γR2 internalization was specific as it did not affect expression of the IFN-γR1 binding chain. Deferoxamine (DFO), an iron-chelating agent, up-regulated IFN-γR2 surface expression and reinstated IFN-γ/STAT1 activation in proliferating T lymphocytes. Resistance of malignant T cells to the antiproliferative effect of IFN-γ in vitro was abrogated by addition of DFO. Conversely, iron inhibited IFN-γ–induced apoptosis in malignant T cells in serum-free conditions. In combination but not individually, DFO and IFN-γ strongly inhibited growth of human malignant T cells in an in vivo severe combined immunodeficient (SCID) mouse model. These data provide valuable insights for novel therapeutic approaches aimed at reinstating the IFN-γ/STAT1 apoptotic signaling pathway in autoreactive or neoplastic T cells by means of iron chelation.
Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies
Authors: Orlowski Robert Z. , Voorhees Peter M. , Garcia Reynaldo A. , Hall Melissa D. , Kudrik Fred J. , Allred Tammy , Johri Anandhi R. , Jones Paul E. , Ivanova Anastasia , Van Deventer Hendrik W. , Gabriel Don A. , Shea Thomas C. , Mitchell Beverly S. , Adams Julian , Esseltine Dixie-Lee , Trehu Elizabeth G. , Green Marie , Lehman Mary Jo , Natoli Susan , Collins Jason M. , Lindley Celeste M. , Dees E. Claire
Published: December 2004

Proteasome inhibitors, a novel class of chemotherapeutic agents, enhance the antitumor efficacy of anthracyclines in vitro and in vivo. We therefore sought to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of bortezomib and pegylated liposomal doxorubicin (PegLD). Bortezomib was given on days 1, 4, 8, and 11 from 0.90 to 1.50 mg/m2 and PegLD on day 4 at 30 mg/m2 to 42 patients with advanced hematologic malignancies. Grade 3 or 4 toxicities in at least 10% of patients included thrombocytopenia, lymphopenia, neutropenia, fatigue, pneumonia, peripheral neuropathy, febrile neutropenia, and diarrhea. The MTD based on cycle 1 was 1.50 and 30 mg/m2 of bortezomib and PegLD, respectively. However, due to frequent dose reductions and delays at this level, 1.30 and 30 mg/m2 are recommended for further study. Pharmacokinetic and pharmacodynamic studies did not find significant drug interactions between these agents. Antitumor activity was seen against multiple myeloma, with 8 of 22 evaluable patients having a complete response (CR) or near-CR, including several with anthracycline-refractory disease, and another 8 having partial responses (PRs). One patient with relapsed/refractory T-cell non-Hodgkin lymphoma (NHL) achieved a CR, whereas 2 patients each with acute myeloid leukemia and B-cell NHL had PRs. Bortezomib/PegLD was safely administered in this study with promising antitumor activity, supporting further testing of this regimen.
Hodgkin lymphoma therapy with interleukin-4 receptor–directed cytotoxin in an infiltrating animal model
Authors: Kawakami Mariko , Kawakami Koji , Kioi Mitomu , Leland Pamela , Puri Raj K.
Published: December 2004

Hodgkin lymphoma represents unique clinicopathologic features because Hodgkin and Reed-Sternberg (H-RS) cells produce a variety of cytokines, express a variety of cytokine receptors, and are surrounded by numerous nonmalignant immunoreactive cells. We found that receptors for interleukin-4 (IL-4R) are highly expressed in H-RS cells. To target interleukin-4 receptor (IL-4R), we used a recombinant protein fusing circularly permuted human IL-4 and Pseudomonas exotoxin termed IL438-37-PE38KDEL, or IL-4 cytotoxin. The cytotoxic effect of IL-4 cytotoxin on H-RS cell lines was determined to be moderate to high in vitro. We developed an infiltrating model of Hodgkin disease (HD) by injecting an adherent population of HD-MyZ cells subcutaneously into the flanks of beige/nude/X-linked immunodeficient mice. The animal model exhibited spontaneous metastasis of H-RS cells to lymph nodes and dissemination to vital organs, including the lungs. Intraperitoneal or intratumoral treatment of these mice with IL-4 cytotoxin resulted in regression of the primary tumor mass and a decrease in the incidence of lymph node metastasis. Mice injected with HD-MyZ cells demonstrated 203% prolonged survival (mean survival, 63 days) compared with control (mean survival, 31 days) when they received systemic IL-4 cytotoxin treatment. Because numerous H-RS cell lines express receptors for IL-4, IL-4 cytotoxin may be a unique agent for the treatment of Hodgkin lymphoma.
Mikromechanisches durchstimmbares Fabry–Perot-Filter für die IR-Gasanalytik (Micromechanical Tunable Fabry–Perot Filter for IR Gas Analysis)
Authors: Neumann Norbert , Heinze Matthias , Stegbauer Hans-Jürgen , Hiller Karla , Kurth Steffen
Published: December 2004

Vorgestellt wird ein kompaktes, durchstimmbares Infrarotfilter, welches als Fabry–Perot-Interferometer (FPI) in 1. Ordnung für den Spektralbereich (3...5) μm ausgebildet ist. Das Filter ist mikromechanisch aus doppelseitig polierten, 300 μm dicken Si-Wafern gefertigt. Die Si-Wafer werden nasschemisch strukturiert und durch Waferbonden gefügt. Als Resonatorspiegel wurden Bragg-Reflektoren gewählt, die aus alternierenden λ/4-Schichten aus SiO2 und Poly-Si aufgebaut sind. Der bewegliche Spiegelträger besteht aus zwei Teilen, um ein Festkörpergelenk aus zwei parallelen Federn zu bilden. Elektrostatische Antriebe lenken den beweglichen Spiegel aus seiner Ruhelage aus und verkleinern den Luftspalt. Durchstimmbare Filter für den Bereich von (4,5...3,0) μm mit einer spektralen Bandbreite von (50...60) nm wurden erfolgreich getestet.
Ein neues preiswertes NDIR-Fotometer mit hoher Langzeitstabilität von Nullpunkt und Empfindlichkeit (A New Inexpensive NDIR Photometer with High Long-Term Stability of Zero Point and Sensitivity)
Authors: Deggim Dieter , Krämer Harri , Olsowski Wolfgang , Zöchbauer Michael
Published: December 2004

Die vorliegende Arbeit beschreibt Konzept sowie Aufbau und Wirkungsweise des neu entwickelten NDIR-Prozessfotometers SIDOR. Besondere Merkmale dieses Fotometers sind sein einfacher Aufbau sowie der stabile Betrieb über ein größeres Wartungsintervall ohne Einsatz von Prüfgasen oder Kalibrierküvetten. Erreicht wurden diese Ziele durch Optimierung des opto-pneumatischen Empfängers, durch Vereinfachung der Konstruktion sowie durch Realisierung eines kompensierenden Signalverarbeitungsverfahrens. Die Leistungsfähigkeit des Gerätes wird anhand von Messbeispielen demonstriert.
Fasergekoppeltes In-situ-Laserspektrometer für den selektiven Nachweis von Wasserdampfspuren bis in den ppb-Bereich (Fibre-Coupled In-situ Laser Absorption Spectrometer for the Selective Detection of Water Vapour Traces down to the ppb-Level)
Authors: Ebert Volker , Teichert Holger , Giesemann Carsten , Saathoff Harald , Schurath Ulrich
Published: December 2004

Ein neues, glasfasergekoppeltes In-situ-Absorptionsspektrometer auf Basis von Nah-Infrarot(NIR)-Diodenlasern eröffnet im Hinblick auf den in Industrie und Forschung bedeutenden In-situ-H2O-Nachweis neue Möglichkeiten, da es erstmals auch in mehrphasigen Gasströmungen die schnelle, selektive, probennahme- und kalibrationsfreie Feuchtemessung gestattet. Aufwändige Tests in der cryogenen Aerosolkammer AIDA ermöglichten mit einer gefalteten Absorptionstrecke von 82 m selbst in dichten Eiswolken eine Nachweisgrenze von 15 ppb (1σ, Δt = 2 s) und demonstrierten gleichzeitig die erste präzise Bestimmung der dynamischen Übersättigung der Gasphase während der Wolkenbildung.
Photoakustische Spektroskopie an farbigen lichtstreuenden Flüssigkeiten (Photoacoustic Spectroscopy on Coloured and Lightscattering Liquids)
Authors: Schloßer Uwe , Schollmeyer Eckhard , Patz Claus-Dieter , Dietrich Helmut
Published: December 2004

Wie die photoakustischen Messungen zeigen, ist es möglich, Spektren zu bestimmen, die herkömmlichen photometrischen Spektren äquivalent sind. Dies konnte durch Messungen an wasserlöslichen Systemen gezeigt werden. Die Messungen an Dispersionsfarbstoffsystemen und naturtrüben Frucht- und Gemüsesäften ergeben qualitative Spektren, die nicht oder nur sehr wenig von lichtstreuenden Effekten überlagert sind. Dies wird zum einen belegt durch photometrische Messungen, die im Vergleich mit PA-Spektren keine farbspezifischen Strukturen im gesamten Wellenlängenbereich aufzeigen. Weiter belegt wird diese Aussage aus den durchgeführten PA-Messungen an Konzentrationsreihen mit Dispersionsfarbstoffsystemen. Diese Spektren haben keinen konzentrationsabhängigen „Offset“ in den Wellenlängenbereichen, in denen keine Absorption vorliegt. Photometrische Messungen an von Textilien extrahierten und gelösten Dispersionsfarbstoffen ergeben Spektren, die qualitativ gleichwertig sind zu PA-Spektren, gemessen an dispergierten Systemen.
Fabrication of glassy carbon microstructures by pyrolysis of microfabricated polymeric precursors
Authors: Schueller Olivier J. A. , Brittain Scott T. , Whitesides George M.
Published: December 2004

High‐carbin mcirostructures as components in microelectromechanical structures and microreactors are of particular interest because their mechanical, electrical, and chemical properties can be controlled by the temperature of preparation. The range of electrical properties is especially impressive. A method of fabricating microstructures of glassy carbon and other high‐carbon solids is presented, based on micromolding of polymers to form precursors to these structures and pyrolysis to yield the carbon solids. The advantages of the technique are discussed.
Simulation of layered double hydroxide intercalates
Authors: Aicken A. Michael , Bell Iain S. , Coveney Peter V. , Jones William
Published: December 2004

Computational simulations of layered double hydroxides (LDHs), based on relatively simple models and simulation procedures (classically based force‐field calculations), are shown to be an effective technique for rationalizing the orientation fo guest species. It is demonstrated that the simulations yield valeus for the gallery heights that agree well with those observed experimentally and that intercalculated water plays an important role. LDHs are of interest for applications in catalysis, medicine, molecular sieing, electrochemistry, and oil‐field exploration.
Access in mesoporous materials: Advantages of a uniform pore structure in the design of a heavy metal ion adsorbent for environmental remediation
Authors: Mercier Louis , Pinnavaia Thomas J.
Published: December 2004

The access of guest species to the binding sites of adsorbent determines the metal‐binding capacity of materials, which is important for example in environmental remediation efforts. It is shown that MP‐HMS, the mercaptopropylsilane‐functionalized derivative of the molecualr sieve HMS, with its regular pore structure is a much better Hg2⊕ absorbent than silica gels, in which functionalization leads to pore blocking (see Figure).

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Brain death: II. Neuropathological correlation with the radioisotopic bolus technique for evaluation of critical deficit of cerebral blood flow
Authors: Pearson John , Korein Julius , Harris James H. , Wichter Melvin , Braunstein Philip
Published: December 2004

Diffuse necrosis and autolysis were found in the brains from 6 comatose, respirator‐supported patients in whom the bolus technique demonstrated no cerebral blood flow during a period exceeding 20 hours prior to cardiac death. When blood flow was insufficient to produce a bolus, there was no evidence of active tissue response to necrosis. In 6 similar patients when cerebral blood flow was detected by the bolus technique, less extensive necrosis was observed postmortem and there was active tissue response.
Distribution of cerebral blood flow in the dominant hemisphere during motor ideation and motor performance
Authors: Ingvar David H. , Philipson Lars
Published: December 2004

Distribution of activity in the dominant (left) hemisphere was studied with a multidetector instrument during diagnostic measurements of regional cerebral blood flow in 6 patients, 4 of them neurologically normal. Computer‐calculated charts, in color, of the flow/activity distribution—“cerebral ideograms”—were obtained in three situations: at rest, during motor ideation (attempts to conceive of rhythmic clenching movements of the right hand), and during actual movements of the right hand. Motor ideation changed the normal “hyperfrontal” resting flow distribution, and an increase of the hemisphere mean flow was recorded. The increase was especially marked in frontal and temporal structures. This pattern differed from the one during actual hand movements, when a rolandic flow increase was seen. The result suggests that centers for motor ideation have a different cerebral location than those which control the actual hand movement.
Sequential cerebral biochemical and physiological events in controlled hypoxemia
Authors: Kogure Kyuya , Scheinberg Peritz , Utsunomiya Yoichi , Kishikawa Hidemi , Busto Raul
Published: December 2004

Effects of controlled hypoxemia on cerebral functional activity were studied in rats using cyclic adenosine monophosphate (cAMP) and aminergic neurotransmitters in the brain tissue as special references. Evidence is presented that: (1) mild hypoxemic stress (Pa 60 to 40 torr) may activate cerebral glycolysis with no evidence of anaerobic metabolism but that further reduction Pa impairs cellular respiration, as evidenced by accumulation of glycolytic products; (2) glycogenolysis in the brain tissue, leakage of potassium ions from the brain cell, increase in brain water, and suppression of neural functional activity occur concomitant with accumulation of cAMP and prior to the fall of adenosine triphosphate; (3) the diminution of cerebral high‐energy phosphates during hypoxia is associated with and may be caused by hypoxemia‐induced neuroglycopenia and occurs at Pa 15 torr; (4) induced hypoxemia per se does not affect the level of aminergic neurotransmitter substances in brain tissue.
The human thalamocortical sensory path in the internal capsule: Evidence from a small capsular hemorrhage causing a pure sensory stroke
Authors: Groothuis Dennis R. , Duncan Gary W. , Fisher C. Miller
Published: December 2004

A patient is presented who suffered a strokelike event during life that resulted in a hemisensory deficit for some modalities. On pathological examination of the brain, the lesion responsible for the deficit was found to be a small slit hemorrhage located in the posterior limb of the internal capsule adjacent to and minimally involving the thalamus. Clinicopathological correlation suggests that the sensory thalamocortical radiations must lie farther posterior in the posterior limb of the internal capsule than the corticospinal motor fibers, and that they probably lie adjacent to the thalamus. The case emphasizes that small slit hemorrhages deep in the brain, although rare, must be considered in the differential diagnosis of sudden hemisensory deficits.
The therapeutic use of glucocorticoid hormones in the perinatal period: Potential neurological hazards
Authors: Weichsel Morton E.
Published: December 2004

The expanding perinatal use of glucocorticoids entails potentially hazardous effects of these hormones on nervous system development. Neonatal animal experimentation with pharmacological doses of glucocorticoids has revealed immediate effects on brain cell division, differentiation, myelination, and electrophysiological reactions. In addition, delayed (latent) effects include changes in control of circadian periodicity, altered biogenic amine levels, altered response to stress, and changes in ultimate behavior. Thus perinatal hormone therapy during critical periods of brain development is capable of exerting irreversible immediate effects on brain cell division and differentiation, resulting in latent or long‐term physiological and behavioral effects.
An electrooculographic study of internuclear ophthalmoplegia
Authors: Kirkham Trevor H. , Katsarkas Athanassios
Published: December 2004

The eye movements of 25 patients with internuclear ophthalmoplegia were recorded by electrooculography. The velocity of adducting saccades was markedly less than normal. The velocity of abducting sacades was within the normal range, but statistically there was a wider distribution. Recordings were made in 2 patients several months after the onset of internuclear ophthalmoplegia, at which time the adducting eye velocity was greater than the abducting eye velocity. A patient with a unilateral medial fasciculus lesion showed marked overshoot of the abducting eye on contralateral saccades and overshoot of both eyes toward the side of the lesion. Optokinetic and postcaloric nystagmus were recorded, and the slow phase showed increasing velocity exponential waveform for the abducting eye. The recordings also showed decreasing velocity exponential waveform for the abducting eye. Downbeat nystagmus was as common as upbeat nystagmus in our patients. The findings appear to confirm the theoretical analysis of the eye movement disorder in internuclear ophthalmoplegia provided by Pola and Robinson as modified by recent experimental work in primates.
Glucocorticoid effects on the edrophonium responsiveness of normal and degenerating mammalian motor nerve terminals
Authors: Hall Edward D. , Riker Walter F. , Baker Thomas
Published: December 2004

An intensive short‐term triamcinolone regimen in cats preserves the prejunctional actions of edrophonium in degenerating motor nerves. These edrophonium actions include the induction of a stimulus‐dependent afterdischarge and the initiation of fasciculations. The relationship between fasciculations and stimulus‐dependent afterdischarge is discussed. The glucocorticoid preservation of these edrophonium effects is like that previously reported for the preservation of posttetanic facilitation in motor nerves equally compromised. The results therefore show that glucocorticoid and facilitatory drug actions synergize to increase facilitation in degenerating but still functional motor nerves. This drug synergy is comparable to that which occurs in normal motor nerves. This interaction may provide a basis for effectively combining glucocorticoid and facilitatory drugs in the treatment of myasthenia gravis.
The relationship of voluntary movement of spasticity in the upper motor neuron syndrome
Authors: Sahrmann Shirley A. , Norton Barbara J.
Published: December 2004

Hyperactive strethch reflexes in the upper motor neuron (UMN) syndrome are frequently cited as an impediment to volitional movement. The assumption is that neural or mechanical activity of the hyperactive antagonist interferes with agonist function. The validity of this assumption was examined by evaluating quantitative and qualitative relationships between stretch reflexes and voluntary movement.

Sixteen patients with chronic UMN symptoms and 8 normal volunteers were tested. Joint position and integrated electromyograms from primary flexors and extensors were recorded. Quantitated values of (1) reflex response to controlled passive motion by an automated system, (2) a maximal voluntary isometric contraction, and (3) the time required for ten voluntary rapid repetitive movements (RRM) of alternating elbow flexion and extension were obtained.

Passive movement elicited tonic reflexes, which predominated during muscle stretch in patients and during muscle shortening in the volunteers. Ratios of the EMG activity elicited during stretch, shortening, and isometric activity were used as measures of spasticity and were compared with the time for RRM. A positive correlation between elbow flexor spasticity and the time for RRM was shown. Qualitative analysis of the EMG activity during voluntary isotonic movement, however, showed that primary impairment of movement is not due to antagonist stretch reflexes, but rather to limited and prolonged recruitment of agonist contraction and delayed cessation of agonist contraction at the termination of movement.
Globoid cells, glial nodules, and peculiar fibrillary changes in the cerebro‐hepato‐renal syndrome of zellweger
Authors: de León Guillermo A. , Grover Warren D. , Huff Dale S. , Morinigo‐Mestre Gladys , Punnett Hope H. , Kistenmacher Mildred L.
Published: December 2004

In addition to a distinct malformation (pachymicrogyria, heterotaxic lamination of the cerebellar cortex, olivary dysplasia), unusual degenerative changes were found in the nervous system of 2 unrelated babies with the Zellweger syndrome. Cerebral clefts were present in 1 case. In both infants there was neuron loss and accumulation of glial nodules and globoid cells in the gray matter as well as degeneration of the white matter. There was fatty change in astrocytes and diffuse gliosis. Neurons in the column of Clarke and the lateral cuneate nucleus showed peculiar fibrillary changes. Cytoplasmic inclusion bodies were seen in the spinal ganglia. Swelling of cortical astrocytes was remarkable in the older infant. The combination of a rare malformation with the cell changes described here gives the syndrome a unique neuropathological profile.
Tables of cranial and orbital measurements, cranial volume, and derived indexes in males and females from 7 days to 20 years of age
Authors: Dekaban Anatole S.
Published: December 2004

A series of head measurements were made in both sexes during the growth period from 7 days to 20 years of age. The measurements included head circumference, breadth, length, and height as well as interpupillary distance and the lateral orbital and medial canthal dimensions; all were expressed as means ± standard deviation in centimeters. In addition, cranial volumes were calculated from the three cranial dimensions according to a previosuly validated formula, and various cranial and orbital indexes were determined for all growth stages.

The increments of all measurements are greatest during the first 12 months of life. At 1 year of age, the cranial volume has increased by a factor of 2.3 and the head circumference, cranial breadth, length, and height by a factor of 1.4 over that at birth. Subsequently the pace of growth slows; at 5 years of age cranial volume has increased up to a total factor of about 3 while head circumference and the other three cranial measurements have expanded by a factor of about 1.5 over the dimensions at birth. By 20 years of age the cranial volume is about 3.8 times that at birth, and the head circumference and the three principal cranial dimensions have increased by a total factor of about 1.6. Clinical applications of the measurements, cranial volume, and certain indexes are listed.
The rate of CSF formation in man: Preliminary observations on metrizamide washout as a measure of CSF bulk flow
Authors: Rottenberg David A. , Howieson John , Deck Michael D. F.
Published: December 2004

Metrizamide, a nonionic, water‐soluble contrast agent, was injected into the ventricular system of 3 patients with indwelling ventricular catheters and subcutaneous cerebrospinal fluid reservoirs. A first‐order rate constant, k, for metrizamide washout from the right lateral ventricle was determined with reference to mean ventricular metrizamide concentration on serial CAT scans; right ventricular volume, V, was estimated after metrizamide injection by multiplying the appropriate ventricular area on consecutive CAT slices by the nominal slice thickness. The rat of right lateral ventricular CSF formation, If, in our 3 patients was calculated as k × V and ranged from 0.83 to 0.103 ml per minute.
The hypothalamus in parkinson disease
Authors: Langston J. William , Forno Lysia S.
Published: December 2004

The hypothalamus was systematically examined in 30 patients with pathologically documented idiopathic parkinsonism. Using Lewy body formation as a marker for nerve cell degeneration, we observed abnormalities in every hypothalamus examined. Of the thirteen hypothalamic nuclei that could be individually identified, none were exempt from Lewy body degeneration. The tuberomamillary nucleus and the lateral and posterior hypothalamic nuclei demonstrated the highest average Lewy body counts (16, 9, and 3, respectively); they were also the most frequently involved nuclei. These findings may aid in interpretation of the autonomic and endocrine abnormalities in patients with Parkinson disease.
Further evidence of a possible association between house dogs and multiple sclerosis
Authors: Cook Stuart D. , Natelson Benjamin H. , Levin Barry E. , Chavis Pamela S. , Dowling Peter C.
Published: December 2004

The present study was undertaken because of the recent report of an association between familial multiple sclerosis (MS) and prior ownership of a small pet. Forty‐five patients with sporadic MS were retrospectively compared with 45 closely matched controls and were found to have owned a significantly greater number of indoor dogs prior to the onset of MS. Importantly, the MS patients had also had more exposure to neurologically ill dogs in the five years before the onset of symptoms. These new data further support the hypothesis that house dogs may serve as an animal vector in MS.
The cervical myelopathy associated with rheumatoid arthritis: Analysis of 32 patients, with 2 postmortem cases
Authors: Nakano Kenneth K. , Schoene William C. , Baker Richard A. , Dawson David M.
Published: December 2004

The clinical findings in a group of 32 rheumatoid patients with symptomatic myelopathy are described. The myelopathy appeared in late middle age after many years of rheumatoid disease (average duration, 18 years). The most common radiological abnormality was anterior subluxation of C1. Other patterns occurred in about half the cases. The most common neurological findings were those of a mild to moderate spastic paraplegia, often with atrophy of muscles of the hands and sensory changes in the hands. Symptoms originating above the foramen magnum (nystagmus, diplopia, slurred speech) appeared to have a vascular cause and were sometimes associated with upward as well as posterior movement of the odontoid process. Root pain into the arms was not present, and its absence helped to distinguish these disorders from cervical spondylosis. Root pain into the territory of the C2 root was common. Medical or conservative therapy was not effective, and the preferred approach was use of a halo traction device followed by posterior fusion, with or without laminectomy. Pathologically, in 2 autopsy cases, the maximal change had occurred in the central gray matter and adjacent posterior and lateral columns. We postulate that direct pressure caused intermittent compression and narrowing of distal transverse branches of the anterior spinal artery.
Gaze‐evoked blepharoclonus
Authors: Keane James R.
Published: December 2004

Painful bilateral orbicularis clonus on eccentric gaze developed in 2 patients with demyelinating disease. This unusual phenomenon was of variable intensity but persisted for years and did not respond to phenytoin or carbamazepine therapy.
Familial degeneration of the basal ganglia with acanthocytosis: A clinical, neuropathological, and neurochemical study
Authors: Bird T. D. , Cederbaum S. , Valpey R. W. , Stahl W. L.
Published: December 2004

Three siblings, offspring of normal consanguineous parents, had a progressive neurological disorder characterized primarily by chorea and leading to death in the fourth or fifth decade. The most carefully studied patient had neither malabsorption nor absent serum β‐lipoprotein but did have erythrocyte acanthocytosis. Postmortern examination showed marked neuronal loss and gliosis of the caudate nucleus and putamen. Activities of glutamic acid decarboxylase and choline acetyltransferase were normal in cortex, caudate, and putamen. Autosomal recessive inheritance, acanthocytosis, and probable peripheral neuropathy help differentiate this disorder from Huntington's disease.
Cationic palladium(II) complexes of ferrocenylphosphines as homogeneous hydrogenation catalysts for olefins
Authors: Cullen William R , Han Nam Fong
Published: January 2005

Cationic palladium(II) complexes of ferrocenylphosphines [(L‐L′)Pd(S)2][ClO4]2 ((L‐L′) = Fe(η5‐C5H4P (C6H5)2)2 1, or Fe(η5‐C5H5)(η5C5H3(CHMeNMe2)P(C6H5)2‐1,2) 2a: S=pyridine or dimethylformamide) were prepared and characterized. The derivatives of 2a are effective catalysts for the hydrogenation of simple olefins at 30°C (1 atm H2). The rate of reduction of styrene depends on the substrate concentration, catalyst concentration and the solvent, and is only slightly inhibited (16%) by the addition of mercury. These observations are conistent with a homogeneous catalytic system.
Organotin compounds: Toxicology and biomedicinal applications
Authors: Saxena Anil K
Published: January 2005

The toxicology and biomedical aspects and applications of organotin compounds are discussed. Factors affecting toxicity are considered first and then the mechanisms of toxicity are described and assessed. A review of the main biomedical applications then follows, covering biochemical, agricultural and other biocidal uses, and recent developments in the field of anticarcinogenesis.
Methylated arsenic species in estuarine porewaters
Authors: Ebdon L , Walton A P , Millward G E , Whitfield M
Published: January 2005

Inorganic arsenic, monomethylarsenic and dimethylarsenic species have been observed in samples of sediment porewater collected from the Tamar Estuary in South‐West England. Porewater samples were collected using in situ dialysis. The arsenic species were separated by hydride generation and concentrated by liquid nitrogen trapping, prior to analysis by directly coupled gas chromatography‐atomic absorption spectroscopy. The predominant dissolved arsenic species present was inorganic arsenic (5‐62 m̈g dm−3). However, this is the first time significant concentrations of methylated arsenic species have been quantified in estuarine porewaters (0.04–0.70 m̈g dm−3), accounting for between 1 and 4% of the total dissolved arsenic. The presence of methylated arsenic compounds in porewaters is attributed to in situ environmental methylation, although the possibility of methylated arsenic species being derived from biological debris cannot be excluded.
Kinetic studies on the reaction of methylcobalamin with metal oxides
Authors: Thayer John S
Published: January 2005

Aqueous solutions of methylcobalamin (CH3B12) react with various water‐insoluble metal oxides. The decomposition of methylcobalamin follows a kinetic pattern of two parallel first‐order reactions. A proposed reaction mechanism involves the attachment of methylcobalamin to the oxide surface, followed by methyl transfer and dissolution of the oxide.
Organotin wood preservatives: Their compatibility with synthetic pyrethroid insecticides
Authors: Blunden S J , Hill R , Patel B N
Published: January 2005

The stability of three synthetic pyrethroids (cypermethrin, deltamethrin and permethrin) to selected tributyltin compounds, Bu3SnX [where X = OSnBu3, Cl, O2CC6H5, O2C(naphthenyl), OSO2C2H5], (Bu3SnO)3PO and (Bu4N) (Bu3SnCl2), in toluene solution was investigated by infrared spectroscopy over a 24‐week period. It was found that only (Bu3Sn)2O reacted with the pyrethroids and that their order of reactivity was cypermethrin>deltamethrin>permethrin. An attempt was made to elucidate the reaction mechanism(s) occurring between (Bu3Sn)2O and the pyrethroids by studying mixtures of this tributyltin fungicide with simple model compounds, R1CO2R2 where R1=CH3; R2=CH2C6H5 and R1=cyclo‐C3H5 and R2=CH2C6H5.
The reactivity of tributyltin oxygen compounds with CCl4: Implications for its use as an extraction/reaction solvent
Authors: Blunden S J , Hill R
Published: January 2005

A variety of tributyltin oxygen compounds,(nC4H9)3SnOX where X = Sn(nC4H9)3, C2H5, nC4H9, C8H17, CH2C6H5, COCH3, have been studied in refluxing CCI4. A reaction was observed to occur where X = C2H5, C4H9, C8H17, CH2C6H5, leading to the formation of (nC4H9)3SnCl, CHCl3 and an aldehyde. Possible reaction pathways are suggested. These reactions have implications for the use of CCl4 as an extraction/reaction solvent.
Synthesis of a novel ferrocene derivative having flame‐retardant and smoke‐suppressant properties
Authors: Carty P , Grant J , Simpson A
Published: January 2005

Reaction of ferrocene with chlorendic anhydride (1,4,5,6,7,7‐hexachloro‐5‐norbornene‐2,3‐dicarboxylic acid anhydride) under Friedel–Crafts reaction conditions affords a new monosubstituted dervative of ferrocene which has significant flameretardant and smoke‐suppressant properties when incorporated into poly(vinyl chloride) (PVC). The monocarboxylic acid from the above reaction undergoes smooth methylation with diazomethane to give the corresponding methyl ester. 1H and 13C NMR spectra of these compounds have been compared with those obtained from similar compounds, namely β‐ferrocenoylpropanoic acid and its methyl ester. Distant asymmetric centres in the chlorendic anhydride substituent markedly affect the proton spectra of the ferrocene derivative.
Biological monitoring of arsenic in semiconductor workers
Authors: Aizawa Yoshiharu , Takata Tsutomu , Kurihara Minoru , Tominaga Mamoru , Inoue Yoko
Published: January 2005

In the manufacture of integrated circuits involving semiconductors, various hazardous materials including arsenic compounds are used. This paper present an evaluation of the biological monitoring of arsenic in the urine, blood and hair of semiconductor workers. Eighty‐two blood samples were obtained from research and development workers in a semiconductor factory. Thirty‐one samples of urine were obtained from the same group of worker before and after a work period (one shift). Seventy‐three hair samples were similarly obtained from the workers. The concentration of arsenic in each sample was determined by arsine (AsH3) generation flame atomic absorption spectrometry after wet ashing of the sample. The mean concentration of arsenic in hair in these semiconductor workers was significantly higher than that of controls. The mean concentration of arsenic in hair from workers with a longer employment duration was higher than from those with a shorter employment duration. The mean concentration of arsenic in hair from workers engaged in epitaxial growth processes was higher than from workers engaged in other processes. The concentrations of arsenic in hair from semiconductor workers correlated with the duration of their employment. The mean concentration of arsenic in urine before a work a period (shift) was not significantly different from that of controls. The mean concentration of arsenic in urine after a work period was in fact lower than that of controls. The mean concentration of arsenic in blood was not significantly different from that of controls. The determination of arsenic in hair is therefore considered useful for the evaluation of relatively long‐term exposure to arsenic in semiconductor workers.
The mechanism of cytotoxicity of methylmercury: Inhibition of progression through the S phase of the cell cycle
Authors: Massaro Edward J
Published: January 2005

The effect of methylmercury (MeHg) on progression of the murine erythroleukemic cell (MELC) through the cell cycle was analyzed by flow cytometry (FCM). Exposure in vitro to 5.0‐10.0 μmol dm−3 MeHg for 6h resulted in a dose‐dependent decrease in the rate of cell replication, apparently as a result of inhibition of DNA synthesis (rate of passage through the S phase of the cell cycle). Thus, only a modest accumulation of cells with a G2/M (4n) DNA content was observed. At or above 10 μmol dm−3 MeHg, progression through all phases of the cell cycle was blocked. FCM revealed a dose‐dependent increase in cellular refractive index (90° light scatter), decrease in apparent cell volume (axial light loss), and increase in resistance to non‐ionic detergent (NP‐40)‐mediated cytolysis indicative of fixation (protein denaturation, cross‐linking, etc.) of the plasma membrane/cytoplasm complex. The data indicate DNA synthesis as the primary target of MeHg cytotoxicity.
Exceptionally high in vitro antitumor activity of substituted triphenyltin benzoates including salicylates against a human mammary tumor, MCF‐7, and a colon carcinoma, WiDr
Authors: Gielen M , Willem R , Biesemans M , Bouǎlam M , Khloufi A El , de Vos D
Published: January 2005

Nine new substituted triphenyltin benzoates of the type Ar3SnOOCC6H2XYZ [X = Y = H, Z = 2‐OCH3 and 4‐F; X = H, Y = 3‐F, Z = 5‐F; X = H, Y = 2‐OH, Z = 5‐Cl, 5‐NH2, 5‐OCH3 and 5‐SO3H; X = 2‐OH, Y = 3‐CH(CH3)2 and Z = 5‐CH(CH3)2] were prepared and possess considerable in vitro antitumor activity against two human tumor cell lines (MCF‐7, a mammary tumor, and WiDr, a colon carcinoma) comparable with that of mitomycin C.