bluuebunny/crossref_metadata_2025 huggingface dataset:
Processing, localization, and requirement of human separase for normal anaphase progression
Authors: Chestukhin Anton , Pfeffer Christian , Milligan Scott , DeCaprio James A. , Pellman David
Published: April 2003

In all eukaryotes, anaphase is triggered by the activation of a protease called separase. Once activated, separase cleaves a subunit of cohesin, a complex that links replicated chromatids before anaphase. Separase and cohesin are conserved from yeasts to humans. Although the machinery for dissolving sister cohesion is conserved, the regulation of this process appears to be more complex in higher eukaryotes than in yeast. Here we report the cloning of full-length human separase cDNA and the characterization of the encoded protein. Human separase was observed at the poles of the mitotic spindle until anaphase, at which time its association with the mitotic spindle was abruptly lost. The dynamic pattern of localization of human separase during cell cycle progression differs from that of fungal separases. Human separase also appears to undergo an autocatalytic processing on anaphase entry. The processed forms of human separase were isolated and the identity of the cleavage sites was determined by N-terminal sequencing and site-directed mutagenesis. The processed catalytic domain was found to be stably associated with the processed N-terminal fragment. Finally, by depletion of endogenous separase with antisense oligonucleotides, we report direct evidence that separase is required for high-fidelity chromosome separation in human cells.
Epigenetic abnormalities associated with a chromosome 18(q21-q22) inversion and a Gilles de la Tourette syndrome phenotype
Authors: State Matthew W. , Greally John M. , Cuker Adam , Bowers Peter N. , Henegariu Octavian , Morgan Thomas M. , Gunel Murat , DiLuna Michael , King Robert A. , Nelson Carol , Donovan Abigail , Anderson George M. , Leckman James F. , Hawkins Trevor , Pauls David L. , Lifton Richard P. , Ward David C.
Published: April 2003

Gilles de la Tourette syndrome (GTS) is a potentially debilitating neuropsychiatric disorder defined by the presence of both vocal and motor tics. Despite evidence that this and a related phenotypic spectrum, including chronic tics (CT) and Obsessive Compulsive Disorder (OCD), are genetically mediated, no gene involved in disease etiology has been identified. Chromosomal abnormalities have long been proposed to play a causative role in isolated cases of GTS spectrum phenomena, but confirmation of this hypothesis has yet to be forthcoming. We describe an i(18q21.1-q22.2) inversion in a patient with CT and OCD. We have fine mapped the telomeric aspect of the rearrangement to within 1 Mb of a previously reported 18q22 breakpoint that cosegregated in a family with GTS and related phenotypes. A comprehensive characterization of this genomic interval led to the identification of two transcripts, neither of which was found to be structurally disrupted. Analysis of the epigenetic characteristics of the region demonstrated a significant increase in replication asynchrony in the patient compared to controls, with the inverted chromosome showing delayed replication timing across at least a 500-kb interval. These findings are consistent with long-range functional dysregulation of one or more genes in the region. Our data support a link between chromosomal aberrations and epigenetic mechanisms in GTS and suggest that the study of the functional consequences of balanced chromosomal rearrangements is warranted in patients with phenotypes of interest, irrespective of the findings regarding structurally disrupted transcripts.
Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by αvβ3 and α5β1 integrins
Authors: Sudhakar Akulapalli , Sugimoto Hikaru , Yang Changqing , Lively Julie , Zeisberg Michael , Kalluri Raghu
Published: April 2003

Tumstatin and endostatin are two inhibitors of angiogenesis derived from precursor human collagen molecules known as α3 chain of type IV collagen and α1 chain of type XVIII collagen, respectively. Although both these inhibitors are noncollagenous (NC1) domain fragments of collagens, they only share a 14% amino acid homology. In the present study we evaluated the functional receptors, mechanism of action, and intracellular signaling induced by these two collagen-derived inhibitors. Human tumstatin prevents angiogenesis via inhibition of endothelial cell proliferation and promotion of apoptosis with no effect on migration, whereas human endostatin prevents endothelial cell migration with no effect on proliferation. We demonstrate that human tumstatin binds to αvβ3 integrin in a vitronectin/fibronectin/RGD cyclic peptide independent manner, whereas human endostatin competes with fibronectin/RGD cyclic peptide to bind α5β1 integrin. The activity of human tumstatin is mediated by αvβ3 integrin, whereas the activity of human endostatin is mediated by α5β1 integrin. Additionally, although human tumstatin binding to αvβ3 integrin leads to the inhibition of Cap-dependent translation (protein synthesis) mediated by focal adhesion kinase/phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 pathway, human endostatin binding to α5β1 integrin leads to the inhibition of focal adhesion kinase/c-Raf/MEK1/2/p38/ERK1 mitogen-activated protein kinase pathway, with no effect on phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 and Cap-dependent translation. Collectively, such distinct properties of human tumstatin and human endostatin provide the first insight into their diverse antiangiogenic actions and argue for combining them for targeting tumor angiogenesis.
The cyclopentenone 15-deoxy-Δ
12,14
-prostaglandin J
2
binds to and activates H-Ras
Authors: Oliva José Luis , Pérez-Sala Dolores , Castrillo Antonio , Martínez Natalia , Cañada F. Javier , Boscá Lisardo , Rojas José M.
Published: April 2003

The cyclopentenone 15-deoxy-Δ
12,14
-prostaglandin J
2
(15d-PGJ
2
) induces cell proliferation and mitogen-activated protein kinase activation. Here, we describe that these effects are mediated by 15d-PGJ
2
-elicited H-Ras activation. We demonstrate that this pathway is specific for H-Ras through the formation of a covalent adduct of 15d-PGJ
2
with Cys-184 of H-Ras, but not with N-Ras or K-Ras. Mutation of C184 inhibited H-Ras modification and activation by 15d-PGJ
2
, whereas serum-elicited stimulation was not affected. These results describe a mechanism for the activation of the Ras signaling pathway, which results from the chemical modification of H-Ras by formation of a covalent adduct with cyclopentenone prostaglandins.
Heterogeneous clearance rates of long-lived lymphocytes infected with HIV: Intrinsic stability predicts lifelong persistence
Authors: Strain M. C. , Günthard H. F. , Havlir D. V. , Ignacio C. C. , Smith D. M. , Leigh-Brown A. J. , Macaranas T. R. , Lam R. Y. , Daly O. A. , Fischer M. , Opravil M. , Levine H. , Bacheler L. , Spina C. A. , Richman D. D. , Wong J. K.
Published: April 2003

Viral replication and latently infected cellular reservoirs persist in HIV-infected patients achieving undetectable plasma virus levels with potent antiretroviral therapy. We exploited a predictable drug resistance mutation in the HIV reverse transcriptase to label and track cells infected during defined intervals of treatment and to identify cells replenished by ongoing replication. Decay rates of subsets of latently HIV-infected cells paradoxically decreased with time since establishment, reflecting heterogeneous lymphocyte activation and clearance. Residual low-level replication can replenish cellular reservoirs; however, it does not account for prolonged clearance rates in patients without detectable viremia. In patients receiving potent antiretroviral therapy, the latent pool has a heterogeneous and dynamic composition that comprises a progressively increasing proportion of stable lymphocytes. Eradication will not be achieved with complete inhibition of viral replication alone.
Drosophila
p53 preserves genomic stability by regulating cell death
Authors: Sogame Naoko , Kim Misoo , Abrams John M.
Published: April 2003

When animal cells are exposed to stressful conditions, the tumor suppressor protein p53 restrains growth by promoting an arrested cell cycle or initiating a cell death program. How these distinct fates are specified through the action of a single protein is not known. To study its functions
in vivo
we produced a targeted mutation at the
Drosophila p53
(
Dmp53
) locus. We show that Dmp53 is required for damage-induced apoptosis but not for cell-cycle arrest. Dmp53 function is also required for damage-induced transcription of two tightly linked cell death activators,
reaper
and
sickle
. When challenged by ionizing radiation,
Dmp53
mutants exhibit radiosensitivity and genomic instability. Hence, elevated mutant loads were not caused by defective checkpoint functions but instead correlated with failures in p53-associated cell death. Our studies support the notion that core ancestral functions of the p53 gene family are intimately coupled to cell death as an adaptive response to maintain genomic stability.
Abbreviated incubation times for human prions in mice expressing a chimeric mouse–human prion protein transgene
Authors: Korth Carsten , Kaneko Kiyotoshi , Groth Darlene , Heye Norbert , Telling Glenn , Mastrianni James , Parchi Piero , Gambetti Pierluigi , Will Robert , Ironside James , Heinrich Cornelia , Tremblay Patrick , DeArmond Stephen J. , Prusiner Stanley B.
Published: April 2003

Transgenic (Tg) mouse lines that express chimeric mouse–human prion protein (PrP), designated MHu2M, are susceptible to prions from patients with sporadic Creutzfeldt–Jakob disease (sCJD). With the aim of decreasing the incubation time to fewer than 200 days, we constructed transgenes in which one or more of the nine human residues in MHu2M were changed to mouse. The construct with murine residues at positions 165 and 167 was expressed in Tg(MHu2M,M165V,E167Q) mice and resulted in shortening the incubation time to ≈110 days for prions from sCJD patients. The construct with a murine residue at position 96 resulted in lengthening the incubation time to more than 280 days for sCJD prions. When murine residues 96, 165, and 167 were expressed, the abbreviated incubation times for sCJD prions were abolished. Variant CJD prions showed prolonged incubation times between 300 and 700 days in Tg(MHu2M) mice on first passage and incubation times of ≈350 days in Tg(MHu2M,M165V,E167Q) mice. On second and third passages of variant CJD prions in Tg(MHu2M) mice, multiple strains of prions were detected based on incubation times and the sizes of the protease-resistant, deglycosylated PrP
Sc
fragments. Our discovery of a previously undescribed chimeric transgene with abbreviated incubation times for sCJD prions should facilitate studies on the prion species barrier and human prion diversity.
The potential influence of organizational and personal variables on customer‐oriented selling
Authors: Martin Craig A. , Bush Alan J.
Published: April 2003

Recent research investigating customer‐oriented selling has indicated that greater attention needs to be focused on organizational or personal antecedents influencing customer‐oriented selling behaviors. Similar to most other departments, a selling department’s environment would include its goals, objectives, and culture, as well as the behaviors, beliefs, and attitudes of top and middle management. Through its corporate culture and environment, the organization’s expectations and requirements are transmitted to its employees, who then implement the organization’s policies and carry out organizational strategies. Therefore, it is apparent that both individual internal environment perceptions and managerial leadership styles could possibly have a significant impact on the level of customer‐oriented selling behavior exhibited by salespeople. Three organizational or personal variables likely related to customer‐oriented selling are examined in the present study. The variables include sales manager leadership style, psychological climate, and empowerment. Each of the variables, and an explanation of its expected relationship with customer‐oriented selling, is explored. Implications for managers from these potential relationships are also provided.
Customer‐oriented cost cutting: process management at Volvo
Authors: Hertz Susanne , Johansson Johny K. , de Jager Flip
Published: April 2003

Drawing on an in‐depth case study of the Volvo automobile company’s strategy in the early 1990s, before the Ford takeover in 1999, this paper demonstrates how policies designed to reduce inventory costs and slim the distribution pipeline can affect a business’ network of suppliers and distributors in unexpected ways. It also shows how the implementation of cost reducing reengineering projects naturally lead to sub‐optimization and a need to consider higher‐level processes. In the Volvo illustration a manufacturer’s reengineering of its distribution chain evolved into a complete recasting of its order fulfillment process, and an adoption of a process management structure. The paper traces the effects on the network of distributors and dealers and shows how Volvo’s new structure curtails the distribution role of foreign sales subsidiaries and shifts their tasks towards market analysis, demand forecasting and customer service in foreign markets. It also shows how a process management perspective impacts a firm’s value chain, marketing function and organizational structure. In the end, the case demonstrates how a division can cut costs and still become more customer‐oriented – and become a more valuable asset for a diversified corporation.
Responses of Single Motor Units in Human Masseter to Transcranial Magnetic Stimulation of Either Hemisphere
Authors: Pearce Sophie L. , Miles Timothy S. , Thompson Philip D. , Nordstrom Michael A.
Published: April 2003

The corticobulbar inputs to single masseter motoneurons from the contra‐ and ipsilateral motor cortex were examined using focal transcranial magnetic stimulation (TMS) with a figure‐of‐eight stimulating coil. Fine‐wire electrodes were inserted into the masseter muscle of six subjects, and the responses of 30 motor units were examined. All were tested with contralateral TMS, and 87 % showed a short‐latency excitation in the peristimulus time histogram at 7.0 ± 0.3 ms. The response was a single peak of 1.5 ± 0.2 ms duration, consistent with monosynaptic excitation via a single D‐ or I1‐wave volley elicited by the stimulus. Increased TMS intensity produced a higher response probability (n= 13, paired t test, P < 0.05) but did not affect response latency. Of the remaining motor units tested with contralateral TMS, 7 % did not respond at intensities tested, and 7 % had reduced firing probability without any preceding excitation. Sixteen of these motor units were also tested with ipsilateral TMS and four (25 %) showed short‐latency excitation at 6.7 ± 0.6 ms, with a duration of 1.5 ± 0.3 ms. Latency and duration of excitatory peaks for these four motor units did not differ significantly with ipsilateral vs. contralateral TMS (paired t tests, P > 0.05). Of the motor units tested with ipsilateral TMS, 56 % responded with a reduced firing probability without a preceding excitation, and 19 % did not respond. These data suggest that masseter motoneurons receive monosynaptic input from the motor cortex that is asymmetrical from each hemisphere, with most low threshold motoneurons receiving short‐latency excitatory input from the contralateral hemisphere only.
Ischaemic Preconditioning Inhibits Opening of Mitochondrial Permeability Transition Pores in the Reperfused Rat Heart
Authors: Javadov Sabzali A. , Clarke Samantha , Das Manika , Griffiths Elinor J. , Lim Kelvin H. H. , Halestrap Andrew P.
Published: April 2003

Opening of the mitochondrial permeability transition pore (MPTP) is thought to be a critical event in mediating the damage to hearts that accompanies their reperfusion following prolonged ischaemia. Protection from reperfusion injury occurs if the prolonged ischaemic period is preceded by short ischaemic periods followed by recovery. Here we investigate whether such ischaemic preconditioning (IPC) is accompanied by inhibition of MPTP opening. MPTP opening in Langendorff‐perfused rat hearts was determined by perfusion with 2‐deoxy[3H]glucose ([3H]DOG) and measurement of mitochondrial [3H]DOG entrapment. We demonstrate that IPC inhibits initial MPTP opening in hearts reperfused after 30 min global ischaemia, and subsequently enhances pore closure as hearts recover. However, MPTP opening in mitochondria isolated from IPC hearts occurred more readily than control mitochondria, implying that MPTP inhibition by IPC in situ was secondary to other factors such as decreased calcium overload and oxidative stress. Hearts perfused with cyclosporin A or sanglifehrin A, powerful inhibitors of the MPTP, also recovered better from ischaemia than controls (improved haemodynamic function and less lactate dehydrogenase release). However, the mitochondrial DOG entrapment technique showed these agents to be less effective than IPC at preventing MPTP opening. Our data suggest that protection from reperfusion injury is better achieved by reducing factors that induce MPTP opening than by inhibiting the MPTP directly.
Hemispheric Control of Territorial Aggression in Anolis carolinensis: Effects of Mild Stress
Authors: Wallace Deckel A.
Published: April 2003

Previous work has demonstrated that the brain of Anolis carolinensis is functionally split, in that the left and right eyes project predominantly to the contralateral hemisphere, and as there are minimal connections between the left and right hemispheres. Using this model, the current experiment examined the effect of mild acute stress on hemispheric regulation of territorial aggression. Thirteen adult male Anolis were paired with an antagonistic males, and eye use and behavioral responses were repeatedly measured during 3 minute behavioral trials. Trials were conducted either after exposure to mild stress, produced by handling the subject, or without stress, and they were run either in the subject’s home cage or in a cage foreign to the subject. Left eye preference for aggressive movements was found during the trials run in the non-stressed conditions (p <0.05). Conversely, stressed subjects showed a reduction in left eye/right hemisphere mediated aggressive movements relative to the non-stressed subjects but no changes in right eye/left hemisphere aggression. This effect was independent of whether or not the subject was in its home or a foreign cage. No laterality in aggressive responding was found when the subjects were placed in separate cages with visual contact. These findings suggest that territorial aggression in Anolis is preferentially initiated and processed by the left eye/right hemisphere but is subject to right-hemispheric inhibition following exposure to acute mild stress.
Trigeminal Projections to the Dorsal Thalamus in a Lacertid Lizard, Podarcis hispanica
Authors: Desfilis Ester , Font Enrique , García-Verdugo Jose Manuel
Published: April 2003

Trigeminothalamic projections in the lizard Podarcis hispanica were investigated by means of biotinylated dextranamine (BDA) injections into different nuclei of the dorsal thalamus. Previous studies of lizards found a projection from the sensory trigeminal nuclei in the brainstem to the nuclei ventromedialis and ventrolateralis of the ventral thalamus. The present results show that, in addition to these projections to ventral thalamic nuclei, neurons of the nucleus of the descending tract and the principal sensory nucleus project contralaterally to the pretectal nucleus lentiformis thalami and bilaterally to the nucleus dorsolateralis anterior thalami of the dorsal thalamus. The contralateral projection to the nucleus dorsolateralis anterior is more developed than its ipsilateral counterpart and appears to be topographically organized. Since the nucleus dorsolateralis thalami has ascending projections to the cortex telencephali, this nucleus may be the thalamic relay of trigeminal sensory information to the telencephalon.
Development and Differentiation of the Anuran Auditory Brainstem during Metamorphosis: An Acetylcholinesterase Histochemical Study
Authors: Kumaresan Vidhya , Kang Christopher , Megela Simmons Andrea
Published: April 2003

The time course of cell differentiation and the presence of histochemically defined areas in brainstem auditory nuclei were examined in developing bullfrogs, Rana catesbeiana, using cresyl violet staining and acetylcholinesterase (AChE) histochemistry. In the medulla, the dorsolateral nucleus (DLN) can be seen as a distinct structure in its adult location only at Gosner stage 40 and beyond. The majority of cells in the DLN are not fully differentiated until late metamorphic climax (stages 45–46) and early postmetamorphosis. The more ventral vestibular nucleus differentiates earlier (stage 37) than the DLN. Adult-like organization of auditory nuclei in the torus semicircularis (TS) of the midbrain cannot be reliably discerned until metamorphic climax stages. Cellular masses in the brainstem reveal AChE from the earliest stage examined (stage 27) but the intensity of staining differs among cell groups. Staining intensity in the DLN is at a peak in recently metamorphosed froglets. The time course of cell differentiation in the DLN precedes slightly or is coincident with the increased, transient presence of AChE. Staining of the superior olive stabilizes at a moderate level in early postmetamorphic stages. Ventral regions of the principal nucleus in the TS stain more intensely than dorsal regions beginning at stage 40. This dorsal-ventral gradient in staining persists in adult stages. There is a transient decline in staining of the laminar nucleus in metamorphic climax stages. Staining intensity in the magnocellular nucleus peaks during stages 40–46 and in early postmetamorphic froglets and then declines in adults, paralleling the pattern seen in the DLN. These data suggest that metamorphic climax and early froglet periods are an important developmental window for major differentiation and maturational events in the auditory brainstem.
Allometric Comparison of the Brain and Brain Structures in the White Crested Polish Chicken with Uncrested Domestic Chicken Breeds
Authors: Frahm Heiko D. , Rehkämper Gerd
Published: April 2003

The feather crest on the head of the White Crested Polish Chicken covers a bony protuberance, a skull modification typical of crested chickens. The telencephalon is displaced into this protuberance, giving the brain the shape of an hour-glass. Allometric comparison (i.e., consideration of the influence of body weight on brain size) shows that the brain is relatively larger in crested chickens. This enlargement is partly due to enlarged ventricles, which are observed in some individuals. Among the brain structures measured, the tegmentum, cerebellum, tectum, paleostriatum, hippocampus, septum and olfactory bulb are not significantly larger in White Crested Polish chickens in comparison to those structures in seven uncrested chicken breeds; the optic tract, diencephalon, telencephalon, accessory hyperstriatum, dorsal and ventral hyperstriatum, and neostriatum, however, are significantly enlarged in this breed.
Incorporation of Dietary Docosahexaenoic Acid into the Central Nervous System of the Yellowtail Seriola quinqueradiata
Authors: Masuda Reiji , Takeuchi Toshio , Tsukamoto Katsumi , Sato Hiroo , Shimizu Ken , Imaizumi Keinosuke
Published: April 2003

In order to show the involvement of docosahexaenoic acid (DHA) in the development of the central nervous system (CNS) in carangid fish, we conducted tracer experiments by feeding radioactive DHA to larval yellowtail (Seriola quinqueradiata). Artemia nauplii were enriched with 14C-labeled DHA and fed to larval yellowtail for eight or ten days. Autoradiography of frozen sections, using both electric imaging plates and X-ray sensitive film, clearly showed that DHA was incorporated into and retained in the brain, spinal cord, and eyes. The brain, eyes, gill raker, liver, guts, and other muscle and bone structures were dissected, and radioactivity was measured in each organ by liquid scintillation counter. The results of this study suggest the incorporation of DHA into the brain. Considering our previous results indicating that DHA-free fish cannot form schools, we conclude that the incorporation of DHA into the brain might be a critical factor in the ontogeny of schooling behavior.
Behavioral, Morphological and Physiological Correlates of Diurnal and Nocturnal Vision in Selected Wading Bird Species
Authors: Rojas L.M. , McNeil R. , Cabana T. , Lachapelle P.
Published: April 2003

We examined in selected wading bird species if diurnal or nocturnal foraging and the use of visual or tactile feeding strategies could be correlated with retinal structure and function. The selected species were the Yellow-crowned Night Heron (Nycticorax violaceus), a crepuscular and nocturnal forager, the Great Blue Heron (Ardea herodias), a mainly crepuscular, but also diurnal and nocturnal feeder, the Roseate Spoonbill (Ajaia ajaja), a mainly crepuscular feeder which forages more at night than during the day, the Cattle (Bubulcus ibis) and Tricolored (Egretta tricolor) egrets and the American White Ibis (Eudocimus ruber) which forage only during daytime. Herons and egrets are visual foragers; ibises and spoonbills are tactile feeders. Electroretinograms were obtained from anesthetized birds in photopic and scotopic conditions to a wide range of light intensities, following which the retinae were processed for histological analysis. Based on rod densities and rods:cones ratios, nocturnal vision capability is greater in the Yellow-crowned Night Heron, followed by the Great Blue Heron and the spoonbill, then by the egrets and the ibis. Visual feeders that forage near dawn or dusk or at night have a higher rods:cones ratio, and consequently a greater night vision capability, than visual feeding species which forage only during daytime. Visual nocturnal feeders have a night vision capability greater than tactile diurnal as well as tactile nocturnal feeders. However, based on maximum scotopic b-wave amplitudes, all species studied have roughly comparable night vision capability. The factor that best discriminates between wading bird species appears to be the daytime visual capabilities. Indeed, the diurnal ibis and egrets have similar cone densities, cones:rods ratios, and photopic a-wave amplitudes, values which are greater than those measured in the two nocturnally active heron species.
Fiber Connections of the Inferior Lobe in a Percomorph Teleost, Thamnaconus (Navodon) modestus
Authors: Shimizu Masakuni , Yamamoto Naoyuki , Yoshimoto Masami , Ito Hironobu
Published: April 2003

Afferent and efferent fiber connections of the lobus inferior (LI) were studied in a percomorph teleost, Thamnaconus (Navodon) modestus. The LI of Thamnaconus is composed of the nucleus diffusus lobi inferioris (NDLI), the nucleus recessus lateralis pars lateralis et medialis (NRLl and NRLm), and the nucleus centralis lobi inferioris pars anterior et posterior (NCa and NCp). The NDLI receives projections from the secondary gustatory nucleus, preglomerular tertiary gustatory nucleus, corpus glomerulosum, dorsal region of the area dorsalis telencephali pars medialis (dDm), and area dorsalis telencephali pars lateralis. Different subdivisions of the dorsal telencephalon project to discrete regions of the NDLI. The NDLI projects to the corpus mamillare, NRLl, NCa, and NCp. Thus the NDLI could be regarded as an intrahypothalamic relay nucleus. The NCa receives projections from the NDLI and projects to the preglomerular tertiary gustatory nucleus, secondary gustatory nucleus, nucleus lateralis valvulae, and NRLl. The NCa appears to be primarily an extrahypothalamic projection nucleus. The NCp receives projections from the NDLI. Efferent connections of the NCp remain to be studied. The NRLl receives projections from the NDLI, and projects to the nucleus ruber (NR) of Goldstein [1905] and the preglomerular tertiary gustatory nucleus. Dense projections of the NR to the stratum opticum and stratum fibrosum et griseum superficiale of the optic tectum are demonstrated. The NRLm receives projections from the medial part of the dDm. Efferent connections of the NRLm remain unclear. The LI as a whole receives projections from the locus coeruleus and nucleus raphe superior. These results suggest that the LI receives gustatory and/or general visceral information from the secondary and tertiary gustatory nuclei, visual and somatosensory inputs from the corpus glomerulosum. Inputs from the dorsal telencephalic subdivisions could be of various modalities (e.g. visual, acousticolateral, gustatory and/or general visceral). The present study also suggests that information processed in the LI is transmitted to the optic tectum via the NR, to the corpus mamillare, to the secondary and tertiary gustatory nuclei, and to the cerebellum via the nucleus lateralis valvulae.
Cross-Species and Intraspecies Morphometric Analysis of the Corpus Callosum
Authors: Olivares Ricardo , Michalland Susana , Aboitiz Francisco
Published: April 2003

A cross-species morphometric study of the corpus callosum was performed in the rat, rabbit, cat, dog, horse, cow and human. Across species, the results indicate a strong, although less than linear, dependency of callosal size on brain weight. This relation tends to lose significance within species. This is consistent with other morphometric studies indicating a tendency to decrease the correlations between morphometric variables in within-species analyses as compared to between-species analyses. There are species differences in the relative size of some callosal segments particularly in the posterior third, which is larger in frontally-looking species than in laterally-looking species. No sex differences in callosal size were detected in any of the species examined. These findings are discussed in the light of possible developmental and functional correlates of the variability observed.
Revisiting the Concept of Identifiable Neurons
Authors: Bullock Theodore Holmes
Published: April 2003

Although eutely in nematodes was known, giant neurons in several taxa and unique motor neurons to leg muscles in decapod crustaceans, the idea that many animals have many identifiable neurons with relatively consistent dynamical properties and connections was only slowly established in the late 1960s and early 1970s. This has to be one of the important quiet revolutions in neurobiology. It stimulated a vast acquisition of specific information and led to some euphoria in the degree and pace of understanding activity of nervous systems and consequent behavior in terms of neuronal connections and properties. Some implications, problems and opportunities for new discovery are developed. The distribution of identifiable neurons among taxa and parts of the nervous system is not yet satisfactorily known. Their evolution may have been a case of several independent inventions. The degree of consistency has been quantified only in a few examples and the plasticity is little known. Identified neurons imply identifiable circuits but whether this extends to discrete systems, functionally definable, seems likely to have several answers in different animals or sites. Very limited attempts have been made to extend the concept to cases of two or ten or a hundred fully equivalent neurons, on all kinds of criteria. These attempts suggest a much smaller redundancy and vaster number of types of neurons than hitherto believed. Theory as well as empirical information has not yet interpreted the range of systems from those with small sets of relatively reliable neurons to those with large numbers of parallel, partially redundant units. The now classical notion of local circuits has to be extended to take account of and find roles for the plethora of integrative variables, of evidence for neural processing independent of spikes and classical synapses, of spatial configurations of terminal arbors and dendritic geometry, of modulators and transmitters, degrees of rhythmicity (regularity varying several orders of magnitude), and of synchrony. Adequate language and models need to go beyond ‘circuits’ in any engineering sense. Identifiable neurons can contribute to a broad spectrum of issues in neurobiology.
Telencephalic Aromatase but Not a Song Circuit in a Sub-Oscine Passerine, the Golden Collared Manakin (Manacus vitellinus)
Authors: Saldanha Colin J. , Schultz J. Douglas , London Sarah E. , Schlinger Barney A.
Published: April 2003

In oscine passerines, the telencephalon expresses high levels of the estrogen synthetic enzyme aromatase. In contrast, forebrain aromatase is limited to low levels at discrete limbic loci in non-passerines. The function of forebrain aromatase in oscines is unknown, however, estrogen-sensitive elements of the telencephalic song circuit (an oscine characteristic) may be influenced by local aromatization. Very few studies have investigated the neuroendocrine characteristics of sub-oscine passerines. Species of this passerine sub-order are taxonomically similar to oscines, but do not appear to learn how to sing as oscines, and show no evidence of a song circuit. The neural expression of aromatase in these birds is unknown. We asked whether the golden-collared manakin, a sub-oscine, (a) showed evidence of a song circuit, and (b) expressed aromatase in the telencephalon at high levels like the zebra finch (oscine passerine) or at low levels like the quail (non-passerine). Nissl stains and immunocytochemistry for microtubule associated proteins showed no evidence of a song circuit in manakins of either sex, whereas both techniques delineate all song nuclei in the zebra finch. However, biochemical and immunocytochemical measures reveal that in the manakin, several telencephalic loci, including the hippocampus, caudomedial neostriatum, nucleus taeniae, and the lateral neostriatum express aromatase. Assays run in parallel show low to undetectable levels of aromatase in the telencephalon of the quail (nonpasserine) and abundant levels in the zebra finch (oscine passerine), suggesting a dissociation between the presence of a song circuit and forebrain aromatase expression in this sub-oscine. These data suggest that forebrain aromatase may have evolved in sub-oscine songbirds before the evolution of a song circuit and singing behavior in oscines. Alternatively, forebrain aromatase may serve functions distinct from singing behavior.
Bacterial Endocarditis at a Tertiary Hospital – How Do We Improve Diagnosis and Delay of Treatment?
Authors: Kjerulf Anne , Tvede Michael , Aldershvile Jan , Høiby Niels
Published: April 2003

During a period of 3.5 years, endocarditis was suspected in 151 patients admitted to Rigshospitalet. 140 were available for this study. In 59 of the 140 patients, the diagnosis was confirmed, and 36 had positive blood cultures. Echocardiographic findings compatible with the diagnosis were present in 92% of the 59 cases. The most common causes of endocarditis were Staphylococcus aureus and viridans streptococci. Patients with endocarditis caused by S. aureus had significantly (p = 0.002) more embolic episodes compared to patients having endocarditis caused by the viridans streptococci. The diagnosis was established at a mean of 3–4 weeks after the onset of symptoms and 2 weeks after admission to hospital. In order to minimize diagnostic delay, the following aspects may be important: (1) earlier detection of endocarditis among physicians examining patients at risk; (2) educating patients with cardiac disease and cardiac valve prosthesis; (3) earlier antibiotic therapy, and (4) developing further diagnostics for endocarditis.
Mechanism of Antiarrhythmic Effects of Class Ic Drugs in Paroxysmal Atrial Fibrillation in Man
Authors: Matsuo Kunihiro , Kumagai Koichiro , Annoura Miyuki , Ideishi Munehito , Arakawa Kikuo
Published: April 2003

While class Ic antiarrhythmic drugs are effective in treating patients with atrial fibrillation, their mechanism of action is poorly understood. We performed electrophysiological studies before and after their administration to 22 patients with paroxysmal atrial fibrillation. Atrial refractoriness, maximal interatrial conduction delay and the wavelength index were measured at two basic cycle lengths (600 or 400 ms). Both drugs studied increased atrial refractoriness and wavelength index. Flecainide reduced the maximal interatrial conduction delay, but pilsicainide did not. Each drug increased the wavelength index in a tachycardia-dependent manner. Class Ic drugs may reduce atrial vulnerability by increasing the wavelength of the reentrant circuit during periods of rapid heart rate.
Surgical Treatment of the Coronary Artery to Pulmonary Artery Fistulas in Adults
Authors: Goto Yoshikazu , Abe Tadaaki , Sekine Satoshi , Iijima Keitarou , Kondoh Katsuyuki , Sakurada Tohru
Published: April 2003

Coronary artery to pulmonary artery fistula (CA-PAF) is a rare congenital anomaly. The purpose of this retrospective study was to analyze 11 adult patients with CA-PAFs treated surgically, and to evaluate the surgical management and long-term results. There were no surgical deaths and all patients survived the follow-up periods (mean 7.2 years). All symptomatic patients improved their New York Heart Association functional class. As surgical correction is safe and effective, with good long-term results, all the patients with CA-PAF in adults can be candidates for surgery to prevent life-threatening complications.
Limitation of Left Ventricular Hypertrophy and Dysfunction by ACE Inhibition after Anterior Q-Wave Myocardial Infarction
Authors: Jugdutt Bodh I. , Humen Dennis P.
Published: April 2003

To determine whether limitation of left ventricular (LV) hypertrophy with angiotensin-converting enzyme inhibition after myocardial infarction (MI) is associated with improved systolic and diastolic function, quantitative two-dimensional echocardiograms and Doppler of 40 patients, who were randomized on day 3 after a first Q-wave anterior MI to receive therapy with captopril (12.5 mg t.i.d.) or placebo for 6 weeks, were analyzed for LV volumes (Simpson’s rule) and mass (3D reconstruction), remodeling parameters and peak early (E) and late (A) transmitral flow velocities and deceleration times (DT) at 3 days, 6 weeks, 6 months and 1 year. Compared to placebo over 1 year, captopril limited (p < 0.001) the increase in diastolic volume and mass, increased LV ejection fraction and diastolic E/A ratio, and decreased DT, the frequency of E and A reversal, infarct expansion and aneurysm frequency but volume/mass ratio was unchanged. Captopril over the first 6 weeks after a first Q-wave anterior MI limited LV remodeling and hypertrophy and improved both systolic and diastolic function up to 1 year.
Left Ventricular Wall Thickening Does Occur in Elite Power Athletes with or without Anabolic Steroid Use
Authors: Dickerman Rob D. , Schaller Frederick , McConathy Walter J.
Published: April 2003

Reports on the occurrence of left ventricular wall thickening in resistance-trained athletes have rejected the possibility for this physiological adaptation to occur without concomitant anabolic steroid abuse. Others have concluded short bursts of arterial hypertension that occur with maximal weight lifting are not sufficient to induce left ventricular wall thickening, and left ventricular wall thickness ≥13 mm should not be found in pure resistance-trained athletes. Therefore, we examined 4 elite resistance-trained athletes by two-dimensional echocardiography. In addition, we retrospectively examined the individual left ventricular dimensions of 13 bodybuilders from our previous echocardiographic studies. All 4 elite resistance-trained athletes had left ventricular wall thicknesses beyond 13 mm. One of the elite bodybuilders has the largest left ventricular wall thickness (16 mm) ever reported in a power athlete. Retrospectively, 43% of the drug-free bodybuilders and 100% of the steroid users had left ventricular wall thickness beyond the normal range of 11 mm. In addition, 1 drug-free subject and 3 steroid users were beyond the critical mark of 13 mm. No subjects demonstrated diastolic dysfunction. In contrast to previous reports, we have demonstrated that left ventricular wall thicknesses ≥13 mm can be found routinely in elite resistance-trained athletes. The use of anabolic steroids concomitant with intensive resistance exercise does appear to augment left ventricular size without dysfunction. Anabolic steroids may accelerate left ventricular wall thickening indirectly by increasing strength, thus augmenting the pressor response.
Cardiac Troponin T Levels at 96 Hours Reflect Myocardial Infarct Size: A Pathoanatomical Study
Authors: Remppis Andrew , Ehlermann Philipp , Giannitsis Evangelos , Greten Tobias , Most Patrick , Müller-Bardorff Margit , Katus Hugo A.
Published: April 2003

We determined the utility of single-point measurements of circulating cardiac troponin T (cTnT) for the noninvasive estimation of infarct size in 16 beagle dogs after left anterior descending artery (LAD) ligation. Pathoanatomical infarct sizes were determined by the triphenyltetrazolium chloride method and correlated with serum concentration changes of cTnT. Peak cTnT levels (14.10 ± 4.71 μg/l) were reached after 110 ± 21 h. A significant correlation was found between peak cTnT levels (p = 0.0001, r = 0.83) or cumulative cTnT levels and relative infarct size (p = 0.0010, r = 0.72). A single cTnT measurement 96 h after LAD ligation was equally predictive of infarct size (p = 0.0010, r = 0.74) as peak or cumulative cTnT levels derived from serial sampling. cTnT levels at 96 h may thus be useful for practical and cost-effective estimation of infarct size.
Helicobacter pylori: In vitro Induction of Resistance to Azithromycin
Authors: Kalenić Smilja , Plečko Vanda , Krešić Sanja , Presečki Vladimir , Tripković Vesna , Žele-Stračević Lidija , Katičić Mirjana , Dominis Mara
Published: April 2003

Helicobacter pylori resistance to macrolides is possibly an important factor for the failure of macrolide therapy for H. pylori infection. The aim of this study was to assess the propensity of H. pylori to develop in vitro resistance to azithromycin. In 73 clinical isolates taken from patients before starting antimicrobial therapy of H. pylori infection, MIC was determined using an agar dilution method (Müller-Hinton agar with 7.5% unlysed horse blood, pH = 7.2, at 35°C, during 72 h in a humid microaerobic atmosphere). Each strain was first cultivated at half minimal inhibitory concentration (MIC) then in doubling concentrations until growth arrest. All experiments for induction of resistance were performed on the same media, incubation temperature, atmosphere and time of MIC determination. MIC interpretative standards for sensitivity, intermediate sensitivity and resistance of H. pylori to azithromycin were ≤2, 4 and ≥8 mg/l, respectively. Of 73 strains, 5 died during the experiments, and in the remaining 68 strains, serial passage with increasing azithromycin concentrations resulted in the development of resistance in 19 (26.9%) strains. Two strains had an MIC of 16 mg/l azithromycin. Thirty-three (48.5%) strains kept the same MIC or doubled their MIC, 16 (23.5%) strains had 4- to 16-fold MIC but still remained sensitive, 2 resistant strains had 128-fold MICs and 17 resistant strains had increased their MICs more than 128 times. Seventeen highly resistant strains (MIC >128 mg/l) were kept frozen at –70°C for 3 months in a brain-heart infusion broth with 15% glycerol. MIC was assessed again to determine the stability of resistance. Eleven strains kept MICs >128 mg/l, 2 became sensitive and 1 intermediate, but reverted easily, after only 2 passages, to an MIC of >128 mg/l azithromycin. Although macrolides are very active against H. pylori, the propensity to develop resistance in a high proportion of strains has a clear impact on the choice of the right combinations of macrolides with other agents as well as the dosage of the macrolide antibiotics.
In vivo Antibacterial Activity of a Prodrug of NM394, a Thiazetoquinoline Carboxylic Acid Derivative
Authors: Ozaki Masakuni , Tomii Yoshifumi , Matsuda Masato , Segawa Jun , Kitano Masahiko , Kise Masahiro , Nishino Takeshi
Published: April 2003

NM394 (6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid) has potent, broad-spectrum antibacterial activity in vitro, but not in vivo. To increase the bioavailability of NM394, various prodrugs were synthesized and tested. One of them, NM441, an N-(5-methyl-2-oxo-1,3-dioxol-4-yl) derivative, showed potent in vivo antibacterial activity. Using thin-layer chromatography-bioautography, we confirmed that after oral administration, NM441 was readily absorbed and hydrolyzed to NM394. Other prodrugs of NM394 were only partially metabolized to NM394. In pharmacokinetic studies in mice and monkeys, we found that the blood levels of NM394 were 7.8 and 5.9 times greater, respectively, when NM441 rather than NM394 was administered. These findings suggest that NM441 is an effective prodrug of NM394.
A Comparative Study of the Cytogenetic and Antineoplasmatic Effects Induced by Carboplatin in Combination with Niacin in Human Lymphocytes in vitro and in Ehrlich Ascites Tumor Cells in vivo
Authors: Mylonaki-Charalambours E. , Mourelatos D. , Kotsis A.
Published: April 2003

Enhanced sister chromatid exchange (SCE) levels and cell division delays were observed when cultured human lymphocytes treated with carboplatin (cPt) were exposed to niacin. Cytogenetic damage was also observed by cPt when Ehrlich ascites tumor (EAT) cells were exposed in vivo to nontoxic concentrations of niacin. One hour before intraperitoneal injection of 5-bromodeoxyuridine, adsorbed to activated charcoal, EAT-bearing mice treaded intraperitoneally with cPt appeared to have a dose-dependent increase in SCEs and cell division delays. Niacin increased the survival time of the EAT-bearing mice treated with cPt and markedly reduced the ascitic volume. Therefore the in vivo antitumor effect of cPt in conjunction with niacin appears to correlate well with the in vitro or in vivo synergistic effects on cytogenetic damage caused by the combined cPt plus Niacin treatment upon human lymphocytes or EAT cells, respectively.
Once-Daily Use of Ofloxacin for Prophylaxis in Breast Cancer Surgery
Authors: Morimoto Ken , Kinoshita Hiroaki
Published: April 2003

The 150 consecutive patients who were hospitalized for breast cancer at our department between September 1992 and November 1995 were enrolled in this open study after having given their informed consent. Patients were assigned randomly to receive ofloxacin in daily doses of 200 mg to be taken in a single dose or a total dose of 600 mg divided into three doses postoperatively for 5 days. Ten patients (8 found to be without malignancies) were excluded from evaluation. Wound infections developed in 8 (12%) of the 69 patients in the 200-mg group and 12 (17%) of the 71 patients in the 600-mg group. Postoperative wound care lasted a median of 19 days (25th and 75th percentiles, 15 and 29 days) for patients given 200 mg and 16 days (13 and 25 days) for those given 600 mg; the difference was not statistically significant (Wilcoxon’s U test). Signs or symptoms suggesting ofloxacin toxicity were not observed, and several significant differences were found in laboratory test results between the two groups both before and after treatment. Abnormal changes after treatment were found in many individuals, but the rate of occurrence was similar in the two groups (U test). When ofloxacin is used for prophylaxis after breast surgery, we recommend a once-daily administration of 200 mg orally for financial reasons and increased patient compliance.