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Intellectual functions and regional cerebral haemodynamics after extensive omental transplantation spread over both frontal lobes in childhood moyamoya disease.

Most accepted operations for childhood moyamoya disease have attempted to increase cerebral blood flow (CBF) in the ischaemic cortical areas around the central fissure. Developed ischaemic brain damage in the prefrontal area may lead to poor intellectual outcome and restrict patients' daily lives. Thus, extensive cerebral revascularization in both the ischaemic anterior and middle cerebral artery territories is mandatory. We describe the long-term follow-up results for intellectual outcome and performance status and make an evaluation of regional cerebral haemodynamics after extensive omental transplantation spread over both frontal lobes performed as the initial management. In the past 10 years, 10 moyamoya patients less than 12 years of age consecutively underwent omental transplantation. The omental flap was spread over not only the symptomatic hemisphere but also the contralateral frontal lobe after a large craniotomy. Superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis was accomplished simultaneously. On the contralateral hemisphere, STA-MCA anastomosis combined with encephalomyosynangiosis was subsequently performed. The clinical observation period averaged 6.7 years (ranged 1.9 to 9.2 years). Apart from 2 patients in whom severe mental retardation had been disclosed pre-operatively, full-scale intelligence quotient scores have been maintained at over 90, that is, within the normal intellectual range. With respect to quality of life (QOL), these 8 patients have been leading normal daily lives since the operation. The focal decrease in CBF observed in the frontal lobe pre-operatively in 7 cases had disappeared after surgical treatment. In these patients, serial post-operative MR angiography revealed developed omental vessels and STAs. Deterioration of intellectual functions and QOL as well as cerebral ischaemic events in paediatric moyamoya patients can be prevented by extensive omental transplantation spread over both frontal lobes combined with STA-MCA anastomosis.

Cerebral Revascularization↗

The relationship between Pepper mottle virus source leaf and spread of infection through the stem of Capsicum sp.

Pepper mottle virus (PepMoV) systemically infects Capsicum sp. in a typical source-to-sink manner with movement through the stem occurring in a predictable pattern. This study was carried out to determine the relationship between the inoculated leaf as a source of inoculum and the spread of PepMoV infection through the stem. C. annuum 'Early Calwonder' plants were mechanically inoculated onto the first leaf with PepMoV and sets of 30 plants had their inoculated leaves removed each day from 1 through 7 days post-inoculation (dpi) with the inoculated leaves tested for infection by ELISA at the time of excision. Beginning at 2 dpi, PepMoV infection in the stem of plants with the inoculated leaf excised and plants of a nonexcision control treatment was determined using immuno-tissue blot analysis. PepMoV was detected in inoculated leaves beginning at 3 dpi with the percentage of infected leaves increasing each day through 7 dpi. PepMoV was first detected in the stem of inoculated plants of the 3 dpi excision treatment. The accumulation and extent of spread of infection in the stem was similar for plants that had their inoculated leaf removed at a time preceding detection by ELISA to plants in the nonexcision control treatment. These findings suggest that once virus is allowed to enter the stem from the inoculated leaf, subsequent spread of infection through the stem is a process independent from the source leaf.

Capsicum↗

A glycoprotein I- and glycoprotein E-deficient mutant of infectious laryngotracheitis virus exhibits impaired cell-to-cell spread in cultured cells.

In alphaherpesviruses, glycoprotein I (gI) and glycoprotein E (gE) form a heterodimer that functions in cell-to-cell spread of the virus. Generally, alphaherpesvirus mutants that lack these glycoproteins are replication competent in cell culture but show a reduced capacity for cell-to-cell spread and hence smaller plaque sizes. Infectious laryngotracheitis virus (ILTV), or Gallid herpesvirus 1, is an alphaherpesvirus that causes respiratory disease in chickens. The roles of gI and gE in ILTV have not been investigated previously. In this study, a glycoprotein I and glycoprotein E deletion mutant of ILTV (gI/gE-ve ILTV) was generated by replacing the region of the ILTV genome coding for the adjacent gI and gE genes with the gene for enhanced green fluorescent protein (eGFP). This gI/E-ve ILTV was readily propagated in cell culture in the presence of wildtype ILTV (wt ILTV). However, in the absence of wt ILTV the propagation of gI/gE-ve ILTV was severely impaired. Infection of permissive cell cultures with gI/gE-ve ILTV failed to produce plaques but single infected cells could be identified by fluorescence microscopy. This suggests that gI/gE has a more significant role in the cell-to-cell spread of ILTV in vitro than in many other alphaherpesviruses.

Animals↗

Altered local and systemic spread of movement deficient virus in transgenic tobacco plants expressing the cucumber mosaic virus 3a protein.

The 3a protein encoded by RNA 3 of cucumber mosaic virus has been identified as the viral cell-to-cell movement protein. The constitutive expression in transgenic tobacco plants of 3a protein from a subgroup I strain was able to complement in trans the short distance movement of a 3a defective CMV mutant belonging to a different taxonomic subgroup. This ability was dependent upon the accumulation levels of the 3a protein in transgenic tobacco plants. However, an initial delay in viral accumulation and spread of the defective virus as compared to the wild type virus was determined in complementation tests. Furthermore, a reduction in disease symptoms as well as a different pattern of systemic viral distribution from those of the wild type virus was detected. These results show that the early events in viral infection affect the long distance spread of the virus. Finally, the wild type virus moved faster in the 3a protein-expressing plants than in control plants, thus indicating that the constitutive expression of the 3a protein favours long-distance viral spread.

Capsid↗

Heterogeneity of p53 mutational status in the superficial spreading type of early gastric carcinoma.

BACKGROUND: The superficial spreading type of gastric carcinoma may originate from either a single cellular clone or from several different clones; this issue remains controversial. Indeed, the p53 gene has been shown to play an important role in gastric carcinogenesis, but there have been only a few reports on the heterogeneity of gastric carcinoma with respect to the p53 gene. METHODS: We analyzed seven cases of the superficial spreading type of gastric submucosal carcinomas (80 lesions; 10 to 17 per case) which showed different histological types and/or different p53 protein staining patterns. Direct sequences of polymerase chain reaction products were used for the analysis. RESULTS: p53 Gene heterogeneity in mucosal carcinoma lesions was detected in three cases. However, in all of the cases, the p53 mutational pattern was identical to that found in the submucosal carcinoma lesions. In the heterogeneous cases, the mutation in the submucosal carcinoma was one of the mutation patterns found among the mucosal carcinoma lesions. More precisely, the mutational pattern of both submucosal carcinoma lesions and the mucosal lesions located just above them, was identical. CONCLUSION: These data suggest that, with regard to the p53 gene, in some superficial spreading types of gastric carcinomas, there are various subclones in the mucosal carcinoma; one of these subclones becomes predominant through clonal selection, and, thus, invades the submucosa.

Aged↗

The role of suppression in the upward spread of masking.

The upward spread of masking refers to the higher growth rate of masking for maskers lower in frequency than the signal, compared to maskers at the signal frequency (Wegel RL, Lane CE. The auditory masking of one pure tone by another and its possible relation to the dynamics of the inner ear. Physics Rev. 23:266-285, 1924; Egan JP, Hake HW. On the masking pattern of a simple auditory stimulus. J. Acoust. Soc. Am. 22:622-630, 1950; Delgutte B. Physiological mechanisms of psychophysical masking: Observations from auditory-nerve fibres. J. Acoust. Soc. Am. 87:791-809, 1990a, Delgutte B. Two-tone rate suppression in auditory-nerve fibres: Dependence on suppressor frequency and level. Hear Res. 49:225-246, 1990b). The upward spread of simultaneous masking may arise from a combination of excitatory and suppressive effects. In this study, growth of masking functions were obtained for a 4-kHz signal masked by an on-frequency (4 kHz) or off-frequency (2.4 kHz), simultaneous or forward masker, in the presence of a notched noise with a center frequency of 4 kHz presented to restrict off-frequency listening. Compression was estimated from the slopes of the off-frequency growth of masking functions. Suppression was estimated by comparing the off-frequency simultaneous- and forward-masked growth of masking functions. Results showed that, for midlevel signals (35-60 dB SPL), the compression exponent estimated from simultaneous and forward masking averaged 0.31 and 0.26, respectively. The maximum amount of suppression (defined as the decrease in the basilar-membrane response to the signal) was variable, ranging from about 6 to 17 dB across subjects. Despite the substantial reduction in the response to the signal, the results suggest that suppression has a minimal effect on the slope of the masking function at mid levels. Rather, upward spread of masking seems to be mainly determined by the compressive basilar-membrane response to the signal in relation to the linear response to the lower-frequency masker.

Acoustic Stimulation↗

Approach for qualitative validation using aggregated data for a stochastic simulation model of the spread of the bovine viral-diarrhoea virus in a dairy cattle herd.

Qualitative validation consists in showing that a model is able to mimic available observed data. In population level biological models, the available data frequently represent a group status, such as pool testing, rather than the individual statuses. They are aggregated. Our objective was to explore an approach for qualitative validation of a model with aggregated data and to apply it to validate a stochastic model simulating the bovine viral-diarrhoea virus (BVDV) spread within a dairy cattle herd. Repeated measures of the level of BVDV-specific antibodies in the bulk-tank milk (total milk production of a herd) were used to summarise the BVDV herd status. First, a domain of validation was defined to ensure a comparison restricted to dynamics of pathogen spread well identified among observed aggregated data (new herd infection with a wide BVDV spread). For simulations, scenarios were defined and simulation outputs at the individual animal level were aggregated at the herd level using an aggregation function. Comparison was done only for observed data and simulated aggregated outputs that were in the domain of validation. The validity of our BVDV model was not rejected. Drawbacks and ways of improvement of the approach are discussed.

Animals↗

MR-determined metabolic phenotype of breast cancer in prediction of lymphatic spread, grade, and hormone status.

The purpose of the study was to evaluate the use of metabolic phenotype, described by high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS), as a tool for prediction of histological grade, hormone status, and axillary lymphatic spread in breast cancer patients. Biopsies from breast cancer (n = 91) and adjacent non-involved tissue (n = 48) were excised from patients (n = 77) during surgery. HR MAS MR spectra of intact samples were acquired. Multivariate models relating spectral data to histological grade, lymphatic spread, and hormone status were designed. The multivariate methods applied were variable reduction by principal component analysis (PCA) or partial least-squares regression-uninformative variable elimination (PLS-UVE), and modelling by PLS, probabilistic neural network (PNN), or cascade correlation neural network. In the end, model verification by prediction of blind samples (n = 12) was performed. Validation of PNN training resulted in sensitivity and specificity ranging from 83 to 100% for all predictions. Verification of models by blind sample testing showed that hormone status was well predicted by both PNN and PLS (11 of 12 correct), lymphatic spread was best predicted by PLS (8 of 12), whereas PLS-UVE PNN was the best approach for predicting grade (9 of 12 correct). MR-determined metabolic phenotype may have a future role as a supplement for clinical decision-making-concerning adjuvant treatment and the adaptation to more individualised treatment protocols.

Adult↗

A model of spatial epidemic spread when individuals move within overlapping home ranges.

One of the central goals of mathematical epidemiology is to predict disease transmission patterns in populations. Two models are commonly used to predict spatial spread of a disease. The first is the distributed-contacts model, often described by a contact distribution among stationary individuals. The second is the distributed-infectives model, often described by the diffusion of infected individuals. However, neither approach is ideal when individuals move within home ranges. This paper presents a unified modeling hypothesis, called the restricted-movement model. We use this model to predict spatial spread in settings where infected individuals move within overlapping home ranges. Using mathematical and computational approaches, we show that our restricted-movement model has three limits: the distributed-contacts model, the distributed-infectives model, and a third, less studied advective distributed-infectives limit. We also calculate approximate upper bounds for the rates of an epidemic's spatial spread. Guidelines are suggested for determining which limit is most appropriate for a specific disease.

Algorithms↗

Pulmonary spread of laryngeal papillomatosis: radiological findings.

Laryngeal papillomatosis is a rare benign disease seen in children and young adults. The spread of laryngeal papillomas throughout the respiratory tract occurs rarely; and involvement of the distal bronchi, bronchioles, and lung parenchyma is very rare. We report a case of pulmonary spread of laryngeal papillomatosis in a 34-year-old man, focusing on the radiological evidence. Chest radiographs showed pulmonary nodules, but computed tomography scans more clearly demonstrated multiple small nodules showing cavitations and distributed centrilobularly. Pulmonary nodules and cavitations progressed gradually through the 6-year follow-up. The combination of clinical and characteristic radiological features suggests a diagnosis of pulmonary spread of laryngeal papillomatosis.

Adult↗

[Pulmonary aspergillosis as initial manifestation of septic granulomatosis (chronic granulomatous disease, CGD) in a premature monozygotic female twin and FDG-PET diagnosis of spread of the disease].

PURPOSE: To present the unusual case of chronic granulomatous disease (CGD) manifestating as pulmonal aspergillosis in female enzygotic twins during the neonatal period. To demonstrate and to discuss the complex diagnosis and the diagnostic value of FDG-PET in monitoring the spread and activity of the disease. PATIENTS: Plain chest x-ray and CT of the lung showed multiple, mostly round lesions in one of the former preterm twins at the age of 8 weeks. The girl with known ASD II was then suffering from dyspnoea and recurrent pulmonary infections. Because of the imaging findings invasive pulmonary aspergillosis due to an underlying immunodeficiency was suspected. RESULTS: Aspergillosis was confirmed histologically and microbiologically by specimens taken from an open lung biopsy. Because of coexisting granulocytic dysfunction the diagnosis of CGD was made. This diagnosis was equally confirmed by noninvasive methods in the asymptomatic sister. FDG-PET did not show any evidence of extra-pulmonary spread of disease. CONCLUSION: CGD can present as isolated pulmonal aspergillosis even in the neonatal period when an immunodeficiency is discussed. In enzygotic twins screening of the asymptomatic twin is mandatory. FDG-PET is a useful tool in screening for spread of the disease and in evaluating disease activity.

Age Factors↗

Spread monolayers of proteins.

The study of spread monolayers of proteins is of interest for understanding the fundamental behavior of proteins as well as the many phenomena resulting from their ubiquitous presence at interfaces in nature. Spread monolayers of proteins is a branch of the developing field of membrane mimetic chemistry. In recent times, it has been somewhat neglected in comparison to other branches (such as bilayers, liposomes and vesicles), despite the unique advantage that the arrangement and packing of molecules in monolayers may be measured and controlled. Methods for spreading proteins and techniques used for their manipulation are outlined. As well as the more traditional methods (such as surface pressure, potential and viscosity), more recent innovations, including removal of monolayers on slides for study by radiotracer techniques, electron diffraction and infrared (IR) spectroscopy, are discussed. Direct optical methods for the study of monolayers in situ are also available (e.g., multiple reflectance spectroscopy, ellipsometry). The use of measurements in the low pressure region to measure molecular weights is discussed. At higher pressures, configurational changes, surface coagulation and desorption are all observed. Experimental and theoretical work on the desorption of proteins from the air/water interface is reviewed. The introduction of multicompartment film balances has proved valuable for the study of reactions occurring in monolayers. This instrumentation has been applied to the study of enzyme reactions at the surface, of direct relevance to reactions where the enzyme is immobilized in the cell membrane. Some applications of monolayer studies are briefly illustrated with reference to biological membranes, foams and emulsions and biomedical problems.

Protein Conformation↗

A biologically active thrombin cleavage product of human serum spreading factor.

Purified human serum spreading factor preparations consisting of two immunologically-related, biologically-active proteins of molecular weights approximately 65,000 and 75,000 were incubated with purified hydrolytic enzymes: papain, neuraminidase and thrombin. Biologically active products of the enzymatic digestions were obtained in each case. Digestion of serum spreading factor preparations with thrombin produced a single active form of molecular weight approximately 57,000. Generation of a single molecular weight form of serum spreading factor by thrombin cleavage of the two higher molecular weight forms should simplify studies of the biochemistry and biology of this protein, and may represent a reaction of physiological significance.

Biological Assay↗

Late spreading of excitation in the lateral geniculate nucleus following visual deafferentation is independent of the size of retinal lesions.

Late spreading of excitation occurs in the lateral geniculate nucleus following partial retinal lesions. The extent of spreading remained the same when reducing the size of the lesions to one fifth. This is incompatible with the idea that the spreading could be caused by displacement of normal cells into the deafferented area as a consequence of transneuronal volume reduction.

Afferent Pathways↗

The effect of light on the spread of signals through the rod network of the salamander retina.

Adjacent rods in the amphibian retina are electrically coupled to each other by gap junctions. By injecting current pulses into one rod and recording the voltage change produced in nearby rods, we have studied the extent to which signals spread between rods in the presence and absence of illumination. Light has little effect on the steady potentials produced in nearby rods by the injection of a hyperpolarizing current, but does affect the propagation of transient signals through the rod network. The responses to injection of depolarizing current are increased by light. These effects of light were mimicked by hyperpolarizing the rod network (non-uniformly) by injecting continuous current (on top of which current pulses were superimposed to monitor signal spread). This suggests that the effects of light are due solely to the rod hyperpolarization produced by light. The effects of light are not completely predicted from computer simulations based on a previous characterization of the properties of isolated rods; these experiments thus reveal an inadequacy in the description of the rod membrane currents in that model. Light-induced hyperpolarization of cones has no effect on signal spread between rods. The functional significance of these results is discussed.

Ambystoma↗

Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum.

This study evaluated the role of excitatory amino acid (EAA) receptor activation in spreading depression (SD), using the in vitro turtle cerebellum as a model system. SD was triggered by electrical stimulation or by elevated K+ after the cerebellum had been conditioned for at least 30 min with physiological saline in which most of the chloride had been replaced by propionate. SD was recognized as a transient (1-3 min) negative shift of extracellular potential accompanied by depression of evoked potentials (15-30 min) and an increase of extracellular K+ up to 60 mM, which spread across the cerebellum at rates of 1-7 mm/min. SD usually commenced in the granular layer, which apparently contains the 3 major EAA receptor subtypes, quisqualate, kainate and N-methyl-D-aspartate (NMDA), then subsequently spread to the molecular layer, which is largely free of NMDA receptors. Glutamate, aspartate, NMDA, kainate and quisqualate all triggered SD. Kynurenic acid and 2-aminophosphonovaleric acid (APV) inhibited SD under certain conditions further suggesting involvement of EAA receptors. The initiation of SD was blocked by high Mg2+ and facilitated in low extracellular Mg2+, which also eliminated the delay in molecular layer SD onset. Our data suggest that no one EAA receptor subtype is singly responsible for SD.

2-Amino-5-phosphonovalerate↗

Self-sustained spreading depressions in the chicken retina and short-term neuronal-glial interactions within the gray matter neuropil.

The chicken retina is an accessible piece of intact gray matter in which a self-sustained form of the 'Spreading Depression' (SD) wave can be easily elicited and recorded for many hours with double barrel ion-sensitive electrodes in the extracellular space. The blockade of glial (Müller) cell potassium channels with barium chloride added to the perfusing Ringer depressed both the negative potential shift typical of SDs and the velocity of spread. Moreover, there was separation of the extracellular increase of potassium and the drop in the extracellular potential: the peak of the potassium wave was increased, as well as its duration whereas the potential wave could be depressed to zero or even inverted to positive. By contrast the transient extracellular calcium drop could not be separated from the extracellular potential wave but appeared related to it: no transient calcium drop was observed when the negative potential was completely depressed or inverted. Both, the amplitude of the extracellular potential and extracellular calcium activity appeared to be important factors controlling the velocity of spread.

Animals↗

Perineural spread of cutaneous squamous cell carcinoma manifesting as ptosis and ophthalmoplegia (orbital apex syndrome).

This paper reports two cases of orbital apex syndrome. The most salient clinical signs, ophthalmoplegia and eyelid ptosis, arose from perineural spread of facial squamous cell carcinomas that were previously excised with tumour-free surgical margins and exhibited no signs of local or other regional recurrence. The interest of these two cases lies in the fairly rare occurrence of this type of tumour spread and the highly aggressive nature of the tumour, unequivocal diagnosis of which usually arrives too late for a surgical solution. Awareness of the possibility of such perineural spread may allow the clinician to establish an early diagnosis and thus undertake radical surgery, thereby increasing the likelihood of success in combination with postoperative radiotherapy.

Aged↗