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Chaos in neuronal networks with balanced excitatory and inhibitory activity.

Neurons in the cortex of behaving animals show temporally irregular spiking patterns. The origin of this irregularity and its implications for neural processing are unknown. The hypothesis that the temporal variability in the firing of a neuron results from an approximate balance between its excitatory and inhibitory inputs was investigated theoretically. Such a balance emerges naturally in large networks of excitatory and inhibitory neuronal populations that are sparsely connected by relatively strong synapses. The resulting state is characterized by strongly chaotic dynamics, even when the external inputs to the network are constant in time. Such a network exhibits a linear response, despite the highly nonlinear dynamics of single neurons, and reacts to changing external stimuli on time scales much smaller than the integration time constant of a single neuron.

Animals↗

Canine parvovirus enteritis 2: Pathogenesis.

Two groups of puppies, eight and 10 weeks of age, were inoculated orally with canine parvovirus of faecal origin. The patterns of faecal excretion of virus, antibody production and systemic viral localisation following inoculation were studied. Faecal excretion of virus was first apparent at day 3 after inoculation, was present most frequently and in greatest quantity at days 4 to 7 after inoculation and fell sharply thereafter. Serum antibody was first detected at day 5 after inoculation with high titres in all samples from day 7 onwards. Virus isolation from serum samples revealed a non-cell associated viraemia at days 3 and 4 after inoculation. Immunocytochemical examination, using both immunofluorescence and immunoperoxidase techniques, first revealed antigen in the thymic cortex at day 1 after inoculation and in the germinal centres of the lymph nodes and the splenic white pulp from days 2 and 3. Viral antigen was first detected in the intestines at day 4 in individual cells in the proliferative zone of the crypt epithelium. From day 5 onwards, the amount of antigen present in the lymphoid tissue decreased so that by days 7 and 8, only a trace was present. There was widespread specific staining in the small intestinal mucosa at day 6, but little antigen was present by day 7. Virus was present in the bone marrow of some dogs killed at days 5 and 6.

Animals↗

Ensemble competitive learning neural networks with reduced input dimension.

Conventional neural networks utilize all the dimensions of the original input patterns for training and classification. However, a particular attribute of the input patterns does not necessarily contribute to classification and may even cause misclassification in certain cases. A new ensemble competitive learning method using the reduced input dimension is proposed. In contrast to the previous ensemble neural networks which adjust learning parameters, the proposed method takes advantage of the information in each dimension of the input patterns. Since the degree of contribution of each attribute to classification is not known beforehand, the different input data sets with one dimension reduced are presented to multiple neural networks. The classification information from each competitive learning neural network is then combined to make a final decision for classification. In order to improve classification accuracy, the ambiguous output neurons are eliminated which cannot be assigned to any class after training. We use three consensus schemes to judge the classification using ensemble neural networks. The experimental results with remote sensing and speech data indicate the improved performance of the proposed method.

Algorithms↗

Initiation and propagation of ectopic waves: insights from an in vitro model of ischemia-reperfusion injury.

The objective of the present study was to directly visualize ectopic activity associated with ischemia-reperfusion and its progression to arrhythmia. To accomplish this goal, we employed a two-dimensional network of neonatal rat cardiomyocytes and a recently developed model of localized ischemia-reperfusion. Washout of the ischemia-like solution resulted in tachyarrhythmic episodes lasting 15-200 s. These episodes were preceded by the appearance of multiple ectopic sources and propagation of ectopic activity along the border of the former ischemic zone. The ectopic sources exhibited a slow rise in diastolic calcium, which disappeared upon return to the original pacing pattern. Border zone propagation of ectopic activity was followed by its escape into the surrounding control network, generating arrhythmias. Together, these observations suggest that upon reperfusion, a distinct layer, which consists of ectopically active, poorly coupled cells, is formed transiently over an injured area. Despite being neighbored by a conductive and excitable tissue, this transient functional layer is capable of sustaining autonomous waves and serving as a special conductive medium through which ectopic activity can propagate before spreading into the surrounding healthy tissue.

Animals↗

Discharge properties of dorsal medullary inspiratory neurons: relation to pulmonary afferent and phrenic efferent discharge.

In decerebrate paralyzed cats ventilated with a cycle-triggered pump system that delivered inflation during the central inspiratory (I) phase (indicated by efferent phrenic discharge), activity of 90 neurons with inspiratory-modulated discharge was recorded in the region of the ventrolateral nucleus of tractus solitarius (vlNTS) in the medulla. Of these, 82 had centrally originating I patterns (69 augmenting, 13 decrementing), and 8 were "pump" neurons. The neurons were classified into functional types by the application of inflation tests, the main test being withholding of the inflation usually delivered during the central I phase. This maneuver eliminated phasic pulmonary afferent input and produced lengthening of the I phase. The neurons' responses were heterogeneous, and were classified as: excitation by inflation (inflation(+], no significant effect of inflation (inflation(0], and depression by inflation (inflation(-]. Application of inflation during the expiratory (E) phase only rarely produced excitation of central I neurons. The I neurons excited by inflation correspond to the "I-beta" neurons of earlier studies. On the basis of the multimodal distribution of their discharge onset times relative to phrenic onset, they were classified as early onset or late onset. In contrast, the inflation(0) and inflation(-) neurons, which correspond to the "I-alpha" neurons, almost exclusively had early onsets. The pump neurons could be distinguished from the inflation(+) I neurons by the effects of inflations delivered during E: the former were equally excited by inflations during E and during I, while the latter were not excited or were minimally excited by inflation during E. Thus, the pump neurons had lung afferent inputs but no inputs from the central I pattern generator, while the inflation(+) I neurons had both kinds of input. The neurons having decrementing discharge during I (early inspiratory and expiratory-inspiratory) were depressed by inflation. Cross-correlation histograms (CCH) of unit firing versus whole phrenic (contralateral and ipsilateral) activity on a short time scale (milliseconds) were computed; the majority of these had high-frequency oscillations, with mean period of 14.6 +/- 3.6 (SD) ms. The CCHs for the different groups of neurons were analyzed with respect to a) strength of correlation as a function of laterality and b) lag of the main correlation peak. Both the inflation(0) and inflation(+) neuronal groups had correlation properties suggesting that these neurons monosynaptically excite phrenic motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Human pattern-evoked electroretinogram.

We have recorded electroretinographic (ERG) responses to grating patterns whose spatial, temporal, and contrast parameters were varied. The resultant evoked potential is dependent on spatial frequency and it exhibits a spatial band-pass characteristic. The peak frequency is dependent on retinal eccentricity. These findings are independent of temporal frequency, contrast, or mean luminance in the photopic range. These results suggest that the pattern ERG originates from a postreceptoral site.

Cerebral Cortex↗

PCR-RFLP-detected human papilloma virus infection in a group of senegalese women attending an STD clinic and identification of a new HPV-68 subtype.

Cancer of the cervix is the most common malignant tumor among women in Africa and, in particular, Senegal. Studies of the prevalence of human papilloma virus (HPV) infection in Africa have mainly focused on carcinomas. Data on the presence of the virus in women with normal cervical cytology are scarce. In this study, 158 cytologically normal women who had been referred to the 'Institut Pasteur de Dakar' (Senegal) for various genital complaints were investigated for the presence of HPV on exfoliated cells by PCR-RFLP. HPV was detected in 13.9% of cases. Oncogenic type HPV 16 was the most common type (40.9%), followed by HPV 53 and HPV 58, both detected in 13.6% of cases. Mixed HPV infections were present in 13. 6% of the subjects. Only HPVs belonging to the intermediate-high risk group were detected. These data suggest the need for careful cytological control of patients. A PCR-HPV fragment (GA115) possessing an original RFLP pattern was isolated. After sequencing, it showed a nucleotide homology of 97.1% with HPV 68 and should therefore be considered a new HPV 68 subtype. The use of PCR-RFLP strategy enables detection and typing of all known and as yet unknown genital HPVs. Variant and subtype classification of HPV types identified by oligonucleotide probe methods may need to be refined, especially for less prevalent HPVs and in areas where little information on HPV prevalence is available. More studies are needed to characterize satisfactorily the epidemiology of HPV in Africa.

Adolescent↗

Castes, migration, immunogenetics and infectious diseases in south India.

It has been said that the grandest genetic experiment of nature has been conducted in south India in the name of the caste system. One can expect the frequency of an infectious disease to be equal to the product of the frequencies of various indicated loci/alleles, whether physiological, hormonal or immunological, in an endemic area. The sympatrically isolated caste and sub-caste populations of southern India, with differing origins, migration patterns and breeding habits, differ significantly in their HLA and other immune repertoire and are ideal models to study and test this hypothesis. The prevalence of a number of major infectious diseases, including TB and leprosy, are reviewed in different communities in the light of their genetic history.

Journal Article↗

Regulation of imprinted DNA methylation.

DNA methylation is an essential enzymatic modification in mammals. This common epigenetic mark occurs predominantly at the fifth carbon of cytosines within the palindromic dinucleotide 5'-CpG-3'. The majority of methylated CpGs are located within repetitive elements including centromeric repeats, satellite sequences and gene repeats encoding ribosomal RNAs. CpG islands, frequently located at the 5' end of genes, are typically unmethylated. DNA methylation also occurs at imprinted genes which exhibit parent-of-origin-specific patterns of methylation and expression. Imprinted methylation at differentially methylated domains (DMDs) is one of the regulatory mechanisms controlling the allele-specific expression of imprinted genes. Proper control of DNA methylation is needed for normal development and loss of methylation control can contribute to initiation and progression of tumorigenesis (reviewed in Plass and Soloway, 2002). Because patterns of imprinted DNA methylation are highly reproducible, imprinted loci make useful models for studying regulation of DNA methylation and may provide insights into how this regulation goes awry in cancer. Here, we review what is currently known about the mechanisms regulating imprinted DNA methylation. We will focus on cis-acting DNA sequences, trans-acting protein factors and the possible involvement of RNAs in control of imprinted DNA methylation.

Animals↗

Meiotic studies in mice carrying the sex reversal (Sxr) factor.

A sex reversal factor (Sxr) that causes mice having apparently normal X chromosomes to become phenotypically male is transmitted in an autosomal pattern. The origin of the Sxr factor is still unknown. It seems most likely that it has originated from an autosomal gene mutation or is the result of a translocation of part of the Y chromosome to one of the autosomes. Chromosomes from four XY and six XO mice carrying this sex reversal factor were examined in the diakinesis stage of meiosis. The following unusual observations were noted: (1) in XY males carrying the Sxr factor, the X and Y chromosomes were separated more often than in controls. (2) The Y chromosome tends to be closer to an autosome when the X and Y are separate than when the X and Y are attached. (3) A chromosome fragment was present in 4/226 cells from two XO males and a single cell from an XY, Sxr carrier. Although there is no direct evidence, these observations seem to favor the possibility that the Sxr factor involves a chromosomal rearrangement rather than a single gene mutation.

Animals↗

Implications of flow cytometry in preoperative detection of biologic variables of gastric cancer and malignant condition of gastric remnant cells obtained by endoscopic biopsy.

Flow cytometric (FCM) DNA studies were performed on cell suspensions obtained by endoscopic biopsy in 73 patients with gastric cancer and in 61 patients with gastric remnant. In cancer, DNA aneuploidies were detected in 49 tumors (67.1%), including 51.7% (15/29) of early gastric cancers and 77.3% (34/44) of advanced gastric cancers. Nuclear DNA content of biopsy materials had a significant correlation with that of surgically obtained ones, providing the estimation of the original ploidy pattern and DNA index (p < 0.01). The serosal invasion, lymph node metastasis, lymphatic invasion, and vascular invasion of the DNA aneuploidy were significantly higher than those of the DNA diploidy (p < 0.05). In patients with gastric remnant, 9 biopsy specimens in the anastomotic site showed DNA aneuploidy (13.9%). The DNA measurement of the endoscopically obtained specimens may provide additional preoperative information and help to identify biologic variables.

Adult↗

Dystrophic degeneration of papillary muscle and ventricular myocardium. A basis for mitral valve prolapse in Duchenne's muscular dystrophy.

The hearts of three children who died with Duchenne's progressive muscular dystrophy and features of mitral valve prolapse were examined to find if the valve disorder arose from cardiomyopathy due to the primary disease or from dystrophic changes in th mitral valve itself. Gross, histologic and ultrastructural features of mitral valve annulus, anterior and posterior leaflets, chordae tendineae, right and left ventricles, and anterior and posterior papillary muscles were compared with those of similar tissues from normal children of matched age and sex. Fibrosis and myofibrillar lysis--most extensive in posterior papillary muscle and in the posterobasal segment of the left ventricle--were the main histopathologic findings. Myofibrillar lysis was characterized by a total loss of actin and myosin myofilaments. By contrast, the mitral valve annulus, its leaflets and the origin, distribution pattern, length and thickness of chordae tendineae were entirely normal. These observations establish that mitral valve prolapse syndrome in Duchenne's dystrophy is an expression of cardiomyopathy involving papillary muscle and ventricular myocardium rather than a result of dystrophic changes in the mitral valve leaflets, annulus or chordae tendineae.

Adolescent↗

Heparin interferes with the biological effectiveness of atriopeptin.

The chromatographic mobility of atriopeptin-28 or of the prohormone is markedly altered by preincubation of the peptides with heparin before separation on reverse-phase high performance liquid chromatography. Protamine prevented the heparin effect and reestablished the original migration pattern of the atrial peptides. The addition of heparin to either rat or human plasma samples did not interfere with the atriopeptin immunoreactivity. The influence of heparin on the biological activity of the atriopeptin-28 in anesthetized rats was also investigated. Infusion of heparin (30 U/min) significantly reduced the dose-dependent fall of blood pressure produced by atriopeptin-28, but did not interfere with the hypotensive effect of nitroglycerin. Similarly, infusion of heparin in volume-expanded rats markedly decreased the diuresis produced by atriopeptin-28 without altering the urine volume excreted in response to furosemide. These data suggest that the highly charged molecule heparin can modify the physical and biological properties of atriopeptins, perhaps by binding to the numerous arginine residues (i.e., 5 arginine residues in atriopeptin-28) in the atriopeptin molecules.

Animals↗

Variations in the anatomy of the rabbit cervical carotid artery.

BACKGROUND AND PURPOSE: A model for cerebral ischemia that requires injection of emboli into the internal carotid artery of the rabbit is commonly used. However, in our experience we have found the anatomy of the cervical carotid to be highly variable. If not appreciated, this may result in unexpectedly high variability in the severity of ischemic injury. We undertook this experimental protocol to determine whether it was possible to characterize the anatomy of the rabbit cervical carotid artery. METHODS: We examined and recorded the architecture of the cervical carotid arteries of 105 consecutive rabbits involved in experimental protocols to evaluate the role of tissue-type plasminogen activator during embolic stroke. RESULTS: Two basic patterns of origin of the internal carotid artery were identified: lateral origin, classified as type I, and dorsomedial origin, classified as type II. In addition, there were three subsequent variations in the origin and morphology of the occipital artery in relation to the internal carotid artery: origin from the external carotid artery (subtype A); origin proximal on the internal carotid artery (subtype B); and origin distal on the internal carotid artery (subtype C). CONCLUSIONS: The classification of the anatomy of the cervical carotid artery of the rabbit into these easily recognized types will assist those attempting to use this embolization model. Failure to recognize the origin of the occipital artery from the internal carotid artery can result in the misdirection of embolic material into the occipital artery and significantly reduce the effectiveness of this stroke model.

Animals↗

Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice.

Hyperthyroidism caused by nodular goiters is a common disease of aging cats. Growth and iodine metabolism were studied by autoradiography in normal and hyperfunctioning thyroid tissue obtained from cats injected with 125I before surgery, and in xenografts, grown in nude mice, after double-labeling with 131I and [3H]thymidine. Hyperthyroid cat goiters contain single or multiple hyperplastic nodules, consisting of highly cellular tissue with an iodine metabolism exceeding that of the surrounding normal tissue. Xenografts of hyperplastic hot tissue in thyroxine-treated nude mice retain their original histologic pattern and continue to accumulate radioiodine intensely. Autoradiographs assessed for [3H]thymidine incorporation reveal autonomously proliferating follicular cells within the hyperplastic foci but not within the normal tissue. Administration of sera from donor cats into host mice fails to stimulate the xenografts. Neither hyperfunction nor growth of toxic cat goiters depends on extrathyroidal stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells.

Animals↗

Support and psychotherapy.

In recent years the psychiatric and psychoanalytical literature has expressed increasing interest in supportive therapy, which has long been considered rather disparagingly as a "lesser form" of psychotherapy. At the same time there has been much reflection on the significance and role of support in various therapeutic settings, outside the formal psychotherapeutic context. A review of updated literature shows, on the one hand, a general appreciation of the idea of support, as an acknowledged component of any therapeutic action. On the other, in the area of psychoanalytic-oriented therapies, there is still debate on the status of supportive psychotherapy, and particularly on the relations between supportive and explorative variants. The eclecticism of supportive therapy and the lack of consensus on its theoretical bases are reviewed in an attempt to develop theoretical/clinical models as the foundation for supportive measures. These potential models would greatly facilitate the transmission and technical application of supportive measures in clinical work. Further research is needed to define the theoretical underpinnings of supportive therapy, establish its origins, the pattern it should take in different therapeutic settings, its potential and limits.

Humans↗

Gender and race differentials in elderly migration.

A number of studies have provided evidence that elderly migration in the United States is strongly selective in terms of the characteristics of the migrants. Such characteristics as age, gender, and race are commonly used in examinations of migrant selectivity, but the differences in spatial behavior of these subpopulations are still poorly understood. This article uses state-to-state migration data, categorized by age, gender, and race, to explore the comparative patterns of origins, destinations, and migration propensities, with a focus on the southeastern states of the country.

Aged↗

Genomic imprinting and assisted reproduction.

Imprinted genes exhibit a parent-of-origin specific pattern of expression. Such genes have been shown to be targets of molecular defects in particular genetic syndromes such as Beckwith-Wiedemann and Angelman syndromes. Recent reports have raised concern about the possibility that assisted reproduction techniques, such as in vitro fertilization or intracytoplasmic sperm injection, might cause genomic imprinting disorders. The number of reported cases of those disorders is still too small to draw firm conclusions and the safety of these widely used assisted reproduction techniques needs to be further evaluated.

Journal Article↗