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PubMedDate not supplied

[Event-related slow potentials (ERSPs) of the brain in cases of temporal psychomotor and petit mal status].

Two cases have been studied by means of the usual method for eliciting CNV (S-1.5 OR 1 SEC-S-operant response) during and after the end of an episode of prolonged epileptic twilight state with almost continuous strictly unilateral temporal lobe discharge. From the clinical viewpoint in both cases the twilight state, lasting respectively about 12 and 48 hours, was characterized by a slightly clouded consciousness and moderate impairment of awareness and of psychic performances, at times associated with simple and complex psychomotor automatism and hallucinations. The EEG recorded an almost continous left temporal discharge of pseudorhythmic mixed slow waves and sharps. The third case had typical prolonged petit mal states with continuous spike-and-slow-wave activity, impaired intellectual and motor performances (very long reaction time etc.). In this patient for eliciting ERSPs, besides the standard method, we have used a paradigm in which S consisted of a colored slide, with various semantic contents, remaining visible for 5 seconds on a screen. At the trials of the standard paradigm during the epiliptic twilight state, all patients showed they had understood the signal to interrupt (S loud repetitive tone) in the shortest time possible and could clearly distinguish them from the S. The operant response was almost always made with sufficient precision and sometimes with fairly short reaction time, especially by the patients with temporal psychomotor status. During the episodes of prolonged clouded consciosness in all series of trials administered to the patients, no negative slow potential shifts were observed in the averaged EEG recordings obtained from F-T, F-T or F, FCZ and referred to to linked mastoids. On repetition of the examinations some time after the end of the epileptic twilight state, fairly normal ERSPs were obtained in all cases. Taking also into account the results of previous researches, these studies show that the temporal lobe and "centrencephalic" epileptic discharges, under certain conditions, may influence negatively the neurophysiological mechanisms which contribute to the information of complex contingent connections and which also underly the particular attentional, cognitive and sensorimotor functions involved in the inhibiting the appearance of ERSPs probably related to more specific perceptual and integrative functions. Some AA. maintain that negative slow potential shifts express the functional activity of the brain structures, particularly of determined cerebral cortex regions, involved not only in attentional, perceptual, cognitive and psychomotor functioning, but also in information processing (memory recording mechanism). Hence, the negative influence of prolonged temporal lobe or meso-diencephalic epileptic discharges on these structures may explain the almost complete amnesia that patients generally show at the termination of this kind of twilight state.

Adult↗

PubMed1994

A simple method using the light microscope to visualize spermatozoon tail swelling in the hypo-osmotic test.

The functional integrity of the sperm (SPTZ) membrane is believed to be an important factor in fertilization. This function was assessed by Jeyendran et al. (Journal of Reproduction and Fertility, 70: 219-228, 1984), who concluded that when SPTZ from normal fertile men are exposed to a hypo-osmotic solution with an ionic strength of 0.15 mol/l, 60% or more will exhibit tail swelling Essentially no changes have occurred in the test procedure since it was first published, except that SPTZ could be fixed after exposure to the hypo-osmotic solution and observed at a later time using a phase-contrast microscope. We describe here a simple test which does not require phase-contrast microscopy to read a stained preparation after the hypo-osmotic test. A drop of semen preincubated in the hypo-osmotic medium of Jeyendran et al. and fixed with 18.5% formalin is placed on an albumin-coated slide. A second (spreader) slide is placed on the first as a coverslip and pulled forward at moderate speed until all the sperm has been spread into a moderately thin film. The preparation is then air dried and submitted to Papanicolaou staining. The slide can be read at any time after staining with a light microscope and provides permanent documentation.

Cell Membrane↗

PubMed1996

Chronic 3-nitropropionic acid treatment in baboons replicates the cognitive and motor deficits of Huntington's disease.

We showed recently that chronic administration of the mitochondrial inhibitor 3-nitropropionic acid (3NP) in primates produces various dyskinetic movements and dystonic postures associated with selective striatal lesions displaying many similarities with the pathological features of Huntington's disease (HD). In the present study, we examined whether such a toxic treatment could also induce frontal-type deficits similar to those observed in HD patients. Cognitive performances of 3NP-treated and control baboons were compared using the object retrieval detour task (ORDT), a test designed to assess the functional integrity of the frontostriatal pathway in human and nonhuman primates. During the same time, the motor function of each animal was assessed under spontaneous "no drug" conditions, and time-sampled neurological observations were used after apomorphine administration. A significant impairment in the ORDT was observed in the 3NP animals after 3-6 weeks of treatment, occurring in the absence of spontaneous abnormal movements by in the presence of apomorphine-inducible dyskinesias. Prolonged 3NP treatment resulted in the progressive appearance of spontaneous abnormal movements. Histological evaluation of these animals showed selective bilateral caudate-putamen lesions with sparing of the cerebral cortex, notably the prefrontal cortex. The present study demonstrates that chronic 3NP treatment replicates in primates the basic pathophysiological triad of HD, including spontaneous abnormal movements, progressive striatal degeneration, and a frontostriatal syndrome of cognitive impairment.

Animals↗

PubMed1999

Oxyhemoglobin as the principal cause of cerebral vasospasm: a holistic view of its actions.

While oxyhemoglobin (oxyHb) is deemed to be the principal cause of cerebral vasospasm following subarachnoid hemorrhage, the mechanism(s) whereby it leads to vasospasm is by no means clear. Of importance is the fact that prolonged contraction of arterial smooth muscle is not the sole feature of cerebral vasospasm, particularly in humans. Vasospasm is also associated with the occurrence of organic changes in the arterial wall as well as the derangement of cerebral microcirculation. These additional features may play a pivotal role when vasospasm in the proximal arteries incurs delayed ischemic neurological deficits and cerebral infarction. The question then arises as to whether or not all the features of vasospasm are attributable to the actions of oxyHb. In this regard, owing to the recent advances in vascular physiology, it has become clear that the cerebral vasculature should be regarded as an organ, not a mere conduit, in which all intracellular mechanisms are functionally integrated for the maintenance and regulation of cerebral blood flow (CBF). In the sense that the arterial function is not simply a sum of the individual cellular functions, it may be described as "holistic". According to extant literature, oxyHb has multifarious actions that can be divided into the following three categories: (1) scavenging of nitric oxide (NO), (2) generation of reactive oxygen species (ROS), (3) activation of the tyrosine kinase/mitogen-activated kinase (TK/MAPK) pathway. Based on such knowledge, the present review aims at a speculative synthesis in terms of how oxyHb pertains to the occurrence of vasospasm, in which the highly integrated, holistic mechanisms within the cerebral artery are perturbed for a prolonged period.

Journal Article↗

PubMed2002

Co-registration of function and anatomy in frameless stereotaxy by contour fitting.

We investigated a co-registration algorithm using a contour-fitting procedure to integrate functional data from magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) for frameless stereotaxy. In fMRI the shape of the head was reconstructed from anatomical images, in MEG it was scanned using an electromagnetic sensor position indicator. Functional information was transferred to the 3D-MR image set used for frameless stereotaxy by fitting the digitized (MEG) and reconstructed head shape (fMRI) to the 3D-MR images. The mean residual error of the contour fit was 2.3 mm for the MEG and 1.3 mm for the fMRI registration. According to computer simulations, the achievable transformation error is 0.75 and 0.5 mm, respectively. This method enables independent recording of functional and anatomical measurements with a co-registration accuracy better than 2 mm.

Brain↗

PubMed1998

Integration of imaging functionality into the healthcare enterprise using DICOM.

The US Department of Veterans Affairs is integrating imaging functionality into the healthcare enterprise using the Digital Imaging and Communication in Medicine (DICOM) standard protocols 1. The VA's VistA Hospital Information System (HIS) is installed at all 170 VA medical centers across the country. Image management is supported by the VistA HIS in several ways. Some VA sites have commercial Picture Archiving and Communication Systems (PACS) interfaced to the VistA HIS, while other sites use the direct image acquisition and diagnostic display capabilities of VistA itself. By supporting a small set of DICOM services, VistA can transmit patient and study text data to the image producing modalities and the commercial PACS, and enable images and study data to be transferred back. Images can be displayed on low-cost clinician's workstations or high-resolution diagnostic quality multi-monitor workstations located within a facility or elsewhere on the healthcare enterprise wide area network. This is a US government work. There are no restrictions on its use.

Costs and Cost Analysis↗

PubMed1993

The visual system and levels of perception: properties of neuromental organization.

To see whether the mental and the neural have common attributes that could resolve some of the traditional dichotomies, we review neuroscientific data on the visual system. The results show that neuronal and perceptual function share a parallel and hierarchical architecture which is manifest not only in the anatomy and physiology of the visual system, but also in normal perception and in the deficits caused by lesions in different parts of the system. Based on the description of parallel hierarchical levels of active information processing in the visual brain, we suggest a concept of dissociable levels of perception, advocating that the phenomenal perception and recognition is realized in the functional integrity of a network of reciprocal cortico-cortical connections. The properties shared by neuronal and perceptional functions provide a basis for a neuromental monism in which both functions are attributed a causal role.

Cerebral Cortex↗

PubMed1997

Changes in baroreceptor vagal reflex performance in the developing rat.

Ontogenesis of both vagal control of heart rate and the baroreceptor vagal reflex were evaluated in rats at postnatal ages (P) of 5/6, 10, 15, 20, 25 and >>42 days anaesthetised with urethane (1.5 g/kg). Between P5/6 and P25 heart rate rose from 372 +/- 12 to 448 +/- 20 beats per minute and mean arterial pressure increased from 33.9 +/- 3.1 to 74.59 +/- 3.25 mm Hg (mean +/- SEM, n = 7 and 11 respectively). Cardiac vagal tone was absent at P10 but significant at P20 (P < 0.05) as revealed with atropine (0.5-1 mg/kg i.v.). Baroreceptor cardiac reflex sensitivity, tested with phenylephrine (10-50 microg/kg i.v.), was attenuated significantly in P10-20 rats compared with P5/6, P25 and mature animals. In P14-17 rats stimulation of neurones in either the solitary tract or ambiguual nuclei, by microinjection of L-glutamate (100-200 pmol), evoked an atropine-sensitive bradycardia indicating a functional integrity of central and peripheral efferent pathways mediating the baroreceptor reflex. Thus, the baroreceptor vagal reflex is functional in P5/6 rats but becomes attenuated between P10-P20, which is coincident with the maturational rise in arterial pressure.

Aging↗

PubMed1983

The infrastructure of aortic elastic fibers.

Elastic fibers are composed of a central core of elastin that is amorphous and electron-lucent in conventional transmission electron micrographs and peripheral microfibrils. A complex infrastructure within the amorphous elastin of mature rat aorta is made visible by fixation and staining with a glutaraldehyde-ruthenium red mixture in phosphate buffer or osmium-ruthenium red in cacodylate buffer. The infrastructure is composed of at least two interlacing but distinct elastic structural components; a framework of circumferentially orientated microfibrils and a three-dimensional meshwork of filaments that permeate the fiber. The latter resembles a reticulum that has previously been observed in freeze-fractured and negatively stained elastin and attributed to the supramolecular organization of elastin. Microfibrils also extend from the core of the elastic fiber into the surrounding matrix where they appear to function as anchoring fibers. These observations indicate that the elastic properties of the arterial wall are an integrated function of both elastin and microfibrils.

Animals↗

PubMed2003

Regulation and roles of phosphoenolpyruvate carboxykinase in plants.

Phosphoenolpyruvate carboxykinase (PCK) is probably ubiquitous in flowering plants, but is confined to certain cells or tissues. It is regulated by phosphorylation, which renders it less active by altering both its substrate affinities and its sensitivity to regulation by adenylates. In the leaves of some C4 plants, such as Panicum maximum, dephosphorylation increases its activity in the light. In other tissues such regulation probably avoids futile cycling between phosphoenolpyruvate and oxaloacetate. Although PCK generally acts as a decarboxylase in plants, its affinity for CO2 measured at physiological concentrations of metal ions is high and would allow it to be freely reversible in vivo. While its function in gluconeogenesis in seeds postgermination and in leaves of C4 and crassulacean acid metabolism plants is clearly established, the possible functions of PCK in other plant cells are discussed, drawing parallels with those in animals, including its integrated function in cataplerosis, nitrogen metabolism, pH regulation, and gluconeogenesis.

Adenosine Triphosphate↗

PubMed1997

Stem cells in prostatic epithelia.

The normal prostate is, structurally and functionally, a highly complex glandular tissue in which populations of epithelial and stromal cells interact, one with the other, and are under a constant state of proliferation, differentiation, elimination and selective secondary replenishment so that functional integrity of the tissue is maintained. The ability of normal prostatic tissue to maintain its structure and function is dependent upon retention of cells, generally regarded as 'stem cells', which are able to respond by proliferation and selective differentiation within a wide range of phenotypic alternatives. With respect to cells in the epithelial compartment, replenishment is possible at several levels from within distinct pathways of normal cellular differentiation. It is now appreciated that fully differentiated prostatic epithelial cells retain a far greater degree of phenotypic 'plasticity' than was earlier apparent from morphological examination of the intact tissue. This inherent plasticity, coupled with the ability of the intact tissue to respond to diverse environmental (particularly humoral) stimuli by regenerating a wide and divergent spectrum of functional prostatic epithelial phenotypes is its strength--but also its weakness. Disturbance and distortion of the homeostatic regulatory mechanisms, whether physical or humoral, which control the normal sequence of epithelial proliferation, differentiation and elimination exposes these cells, particularly multipotent 'stem cells', to an increased probability of genetic change, thus resulting in either transient, or permanent, neoplastic transformation.

Basement Membrane↗

PubMed2003

The SKHR motif is required for biological function of the VirR response regulator from Clostridium perfringens.

The response regulator VirR and its cognate sensor histidine kinase, VirS, are responsible for toxin gene regulation in the human pathogen Clostridium perfringens. The C-terminal domain of VirR (VirRc) contains the functional FxRxHrS motif, which is involved in DNA binding and is conserved in many regulatory proteins. VirRc was cloned, purified, and shown by in vivo and in vitro studies to comprise an independent DNA binding domain. Random and site-directed mutagenesis was used to identify further amino acids that were required for the functional integrity of the protein. Random mutagenesis identified a unique residue, Met-172, that was required for biological function. Site-directed mutagenesis of the SKHR motif (amino acids 216 to 219) revealed that these residues were also required for biological activity. Analysis of the mutated proteins indicated that they were unable to bind to the DNA target with the same efficiency as the wild-type protein.

Amino Acid Motifs↗

PubMed2006

Generation of mice harbouring a conditional loss-of-function allele of Gata6.

The zinc finger transcription factor GATA6 is believed to have important roles in the development of several organs including the liver, gastrointestinal tract and heart. However, analyses of the contribution of GATA6 toward organogenesis have been hampered because Gata6-/- mice fail to develop beyond gastrulation due to defects in extraembryonic endoderm function. We have therefore generated a mouse line harbouring a conditional loss-of-function allele of Gata6 using Cre/loxP technology. LoxP elements were introduced into introns flanking exon 2 of the Gata6 gene by homologous recombination in ES cells. Mice containing this altered allele were bred to homozygosity and were found to be viable and fertile. To assess the functional integrity of the loxP sites and to confirm that we had generated a Gata6 loss-of-function allele, we bred Gata6 'floxed' mice to EIIa-Cre mice in which Cre is ubiquitously expressed, and to Villin-Cre mice that express Cre in the epithelial cells of the intestine. We conclude that we have generated a line of mice in which GATA6 activity can be ablated in a cell type specific manner by expression of Cre recombinase. This line of mice can be used to establish the role of GATA6 in regulating embryonic development and various aspects of mammalian physiology.

Alleles↗

PubMed2001

Biodistribution and dosimetry of pretargeted monoclonal antibody 2D12.5 and Y-Janus-DOTA in BALB/c mice with KHJJ mouse adenocarcinoma.

UNLABELLED: Biodistribution and dosimetry of 88Y (and equimolar 90Y) Janus-dodecanetetraacetic acid (DOTA) were performed using a three-step pretargeting protocol in BALB/c mice bearing mouse mammary adenocarcinoma (KHJJ) implants. Pretargeting was performed with mouse monoclonal antibody (mAb) 2D12.5 specific for yttrium-DOTA, and the chase was Y-DOTA-human transferrin conjugate. In this article, we report extensive organ dosimetry and the theoretic limits of the radionuclide physical half-life (T(p)) for pretargeting. METHODS: Organ biodistribution data were obtained from bioassays on tissue taken from tumor mice killed at 3, 24, 48, 72, 96, and 120 h after intravenous injection of 88Y-Janus-DOTA. Uptake and retention of 88Y as a function of time were described by nonlinear least squares fits of the tissue data to multiexponential functions. Radiation dose estimates for equivalent molar amounts of 90Y were subsequently derived from these time-integrated functions. RESULTS: The results were as follows: rapid blood clearance of 88Y-Janus-DOTA; rapid uptake and slow clearance of 88Y-Janus-DOTA from the tumor over 5 d; rapid clearance from all organs and body; largest radiation absorbed dose (AD) per injected dose of 63.52 (cGy/MBq) to tumor; high therapeutic ratios (AD tumor/AD tissue), particularly for blood and bone; and optimal radionuclide T(p) range from 30 min to 10 d. CONCLUSION: Although the absolute concentration of 90Y in the tumor is less using the hapten system than is achieved generally with the chelated radionuclide covalently attached to the mAb, the achievable tumor uptake of radioactivity, coupled with low radioactivity in bone, blood, and other organs, suggests that a three-step pretargeting protocol has considerable promise as a method for 90Y radioimmunotherapy.

Adenocarcinoma↗

PubMed1994

Islet isolation and autotransplantation in pigs.

Despite recent considerable progress in the isolation and purification of porcine pancreatic islets the final proof of functional integrity has not yet been performed. In the present study the feasibility, technical problems and posttransplant metabolic function of islet transplantation in the pig were investigated. Intraductal collagenase perfusion technique for islet preparation was used in 27 landrace pigs and eight minipigs followed by intraportal or intrasplenic transplantation of the islets. Islet purification was performed by dextran gradient in six preparations. Islet quantification, portal vein pressure measurements, intra- and postoperative complications and postoperative graft function were monitored. Between 1.73 x 10(5) and 11.4 x 10(5) islet containing fragments (8.23 x 10(3)-54.28 x 10(3) islet containing fragments/kg recipient body weight) were transplanted. Portal vein thrombosis occurred in 4 animals with significantly elevated portal pressure (p = 0.0001). 11 of 27 landrace pigs died due to postoperative complications. None of the minipigs was lost due to perioperative mortality (p = 0.031). Four of eight landrace pigs with intrasplenic grafts (50%) were normoglycemic and two of eight landrace pigs with intrahepatic transplants (25%) were normoglycemic. In minipigs two out of four (50%) with intrasplenic transplants and two of four (50%) with intraportal transplants were normoglycemic. The results in glucose metabolism as measured with intravenous glucose tolerance tests and calculated by K-values were statistically significantly different between normoglycemic and hyperglycemic animals (landrace pigs p = 0.0002 and minipigs p = 0.0005). Longevity was prolonged in normoglycemic animals as compared to hyperglycemic and apancreatic animals. It is concluded that successful islet isolation and transplantation is feasible in the landrace pig and the minipig while the landrace pig appears to be more susceptable to perioperative mortality.

Animals↗

PubMed1998

Carbon disulfide neurotoxicity in rats: VII. Behavioral evaluations using a functional observational battery.

The neurobehavioral consequences of inhalational exposure to carbon disulfide (CS2) were evaluated as part of a joint project between the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency. Behavioral changes in rats were measured using a functional observational battery (FOB), which is a series of observations and manipulations designed to assess the neuronal integrity of autonomic, motor, sensory, and integrative functions. Young adult male and female Fischer-344 rats were exposed to one of four CS2 concentrations (0, 50, 500, or 800 ppm, six hours/day, five days/week) and tested at the end of one of several exposure durations (two, four, eight, or 13 weeks). All rats were also tested before exposure began to obtain baseline values. Neuromuscular deficits which were more pronounced in the hindlimbs, e.g., decreased strength and gait alterations, were detected in rats of both sexes. These changes were closely related to CS2 concentration and exposure duration, with mild gait changes evident after only two weeks of exposure. Other effects, mostly observed at 13 weeks, included decreased responsiveness to a visual stimulus and mild tremors. Reactivity in response to handling was generally increased, and excitability in the open field was decreased, in rats tested after the shorter exposures (two and four weeks). Thus, the exposure-concentration and -duration characteristics of the neuromotor syndrome produced by CS2 were detected and defined using the FOB. These studies provide a more complete evaluation of rats under these CS2 exposure conditions, which can then be used to compare with other mechanistic-related endpoints from this collaborative study.

Administration, Inhalation↗

PubMed2005

Cardiac systems biology.

As more detailed molecular information accumulates on the biology of the heart and other complex systems in health and disease, the need for new integrative analyses and tools is growing. Systems biology and bioengineering seek to use high-throughput technologies and integrative computational analysis to construct networks of the interactions between molecular components in the system, to develop systems models of their functionally integrated biological properties, and to incorporate these systems models into structurally integrated multi-scale models for predicting clinical phenotypes. This review gives examples of recent applications using these approaches to elucidate the electromechanical function of the heart in aging and disease.

Aging↗

PubMedDate not supplied

Altered responsiveness to alcohol after exposure to organic lead.

Ethyl alcohol is known to effect the functional integrity of the limbic system, particularly the hippocampus, and to alter behaviors which are thought to be mediated through limbic function. Organometals also compromise the limbic system and result in deficits in learning and memory. Since both alcohol and organoleads are present in the environment and seem to influence limbic integration, the interaction of these two compounds was assessed in the present experiment. Thirty male rats of the Fischer-344 strain were divided into three equal groups and were given injections of trimethyl lead (TML) (8.0 or 17.0 mg/kg/ml SC) or the saline vehicle. Fourteen days later, all animals were challenged with a single hypnotic dose of ethanol (3.5 g/kg IP). The 20% v/v solution of alcohol was prepared in water from a stock solution of 95% ethanol. The latency to loss of the righting reflex and duration of sleep time were recorded while the rats were kept in sound-attenuating chambers. The rats treated with the highest dose of TML manifested significantly longer latencies to lose the righting reflex and shorter durations of sleep than did controls. These results suggest that exposure to environmental lead may alter the biological and behavioral responsiveness of an animal to alcohol.

Animals↗