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PubMed1993

Expression of type XIV collagen during the differentiation of fetal bovine skin: immunolabeling with monoclonal antibody is prominent in morphogenetic areas.

Type XIV collagen belongs to the subclass of fibril-associated collagens with interrupted triple helices, which are composed of alternative triple helical and non-collagenous domains. Structural data show that these molecules interact with collagen fibrils and suggest that they might interact with cells. We have investigated the expression of type XIV collagen in bovine skin during development. Fetuses from 9 to 37 weeks were examined. Anti-type XIV collagen monoclonal antibody was produced, characterized, and used for immunofluorescence detection of the molecule. The localization of immunolabeling was analyzed by comparison with light and electron microscopic observations. In 9-week-old fetus, no type XIV collagen was found in the skin. From 19 weeks to birth, extensive immunofluorescence was observed on bundles of collagen fibrils in deep dermis. As shown by electron microscopy, this area exhibited bundles of collagen fibrils and cells with an abundant rough endoplasmic reticulum. In the upper dermis, a delicate fibrillar network of type XIV collagen was revealed by immunofluorescence around growing hair follicles at 19 and 24 weeks. Double labeling for type XIV collagen and fibronectin shows a more restricted pattern of expression of type XIV collagen in this area. The electron microscopic examination of skin of fetuses at these stages shows that the whole upper dermis is composed by a loose connective tissue containing scattered small bundles of collagen fibrils. Type XIV collagen was synthesized in the upper dermis between 24 weeks and birth. From this study, it appears that type XIV collagen expression is distinct from that of fibrillar collagens, at least during some developmental events. The prominent localization of type XIV collagen around growing hair follicles suggests a role for this molecule in epithelial-mesenchymal interactions.

Animals↗
PubMed2005

Intrafollicular paracrine communication in the zebrafish ovary: the state of the art of an emerging model for the study of vertebrate folliculogenesis.

The development and function of vertebrate ovary are primarily controlled by the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the pituitary. However, most of the activities of FSH and LH are mediated or modulated by a variety of locally produced factors that form an intimate regulatory network within and between the follicles. As a top vertebrate model for genetic and developmental studies, the zebrafish has caught tremendous attention in the past two decades; however, its utility has quickly been extended to other areas including physiology. In the past few years, a variety of peptide growth factors have been identified and characterized in the zebrafish ovary including activin and epidermal growth factor (EGF), and lines of evidence point to the existence of an ovarian network of communication involving these factors. This article provides the state of the art of zebrafish as a model for analyzing ovarian development and its regulation.

Animals↗
PubMed2005

Neuro-modulation, aminergic neuro-disinhibition and neuro-degeneration. Draft of a comprehensive theory for Alzheimer disease.

A comprehensive theory for Alzheimer disease (AD) which can provide a clue to the neuronal selective vulnerability (pathoklisis) is still missing. Based upon evidence from the current literature, the present work is aimed at proposing such a theory, namely the 'aminergic disinhibition theory' of AD. It includes data-based hypotheses as to the pathoklisis, mechanisms of neuro-degeneration and dementia as well as the aetiology of the disease. Alzheimer disease is regarded as a disorder of neural input modulation caused by the degeneration of four modulatory amine transmitter (MAT) systems, namely the serotoninergic, the noradrenergic, the histaminergic, and the cholinergic systems with ascending projections. MATs modulate cognitive processing including arousal, attention, and synaptic plasticity in learning and memory, not only through direct, mostly inhibitory impact on principal neurones but also partially through interaction with local networks of GABA-ergic inter-neurones. The distribution and magnitude of the pathology in AD roughly correlate with the distribution and magnitude of MAT modulation: Regions more densely innervated by ascending MAT projections are, as a rule, more severely affected than areas receiving less MAT innervation. Because the global effect of MATs in the forebrain is inhibition, the degeneration of four MAT systems, some related peptidergic systems and a secondary alleviation of the GABA-ergic transmission means a fundamental loss of inhibitory impact in the neuronal circuitry resulting in neuronal (aminergic) disinhibition. Clearly, the basic mechanism promoting neuronal death in AD is thought to be a chronic disturbance of the inhibition-excitation balance to the advantage of excitation. Chronic over-excitation is conceived to result in Ca2+ dependent cellular excito-toxicity leading to neuro-degeneration including amyloid-beta production and NFT formation. Disinhibited neurons will degenerate while less excited (relatively over-inhibited) neurones will survive. Because the decline of aminergic transmission in AD is likely to start at the receptor level, it is hypothesized that early impairment by a molecular 'hit' to an MAT receptor (or a group of receptors) initiates a pathogenetic cascade that develops in an avalanche-like manner. Based on experimental evidence from the literature, the 'hit' might be the attachment of a targeted pathogen like a small roaming amino acid sequence to the receptor(s), e.g., the serotoninergic 5-HT2A-R. Referential sequence analysis could be a means to identify such a small pathogen hidden in a large receptor molecule.

Alzheimer Disease↗
PubMed1999

Better by half: hypertension in the elderly and the 'rule of halves': a primary care audit of the clinical computer record as a springboard to improving care.

BACKGROUND: Despite recent studies highlighting the benefits of treating elderly hypertensives, researchers have shown that the taking on board of these findings has been disappointing in primary care, where the 'rule of halves' still applies. Clinical computers could help performance in this area, yet national and local research suggests that they are under-used. OBJECTIVE: Our aim is to develop a pragmatic intervention which aims to: improve patient care by translating research findings into practice, increase meaningful computer use, establish 'paperless' annual audits and improve 'networking' between practices. METHOD: Following a baseline audit to ascertain accuracy, the computer records of participating practices were tested against the 'rule of halves' for hypertension. Results were presented to each practice (individual practice and aggregate data for all practices). Management guidelines, standardization of computer recording, achievable targets and review dates were agreed. The study was conducted in West London practices using the EMIS computer system in 1996/1997. RESULTS: An 81% (22/27) practice response rate was achieved. Baseline audit was completed for 22 practices. Fifteen practices appear to be using their computer regularly (two-thirds). Using strict definitions, 'the rule of halves' still applies. Using looser definitions, three-quarters of hypertensives are known, two-thirds are treated and just under two-thirds are controlled. This project identified wide inter- and intra-practice variation in: use of the computer, patient follow-up, attainment of target BP, rounding BP readings to target levels and prescribing patterns. CONCLUSION: This focused training intervention has introduced practices to evidence-based proactive care and highlighted an important application for clinical computers. A local network of practices has been established for future projects. For elderly patients registered with a GP, the rule of halves has been improved upon, provided that a figure of 160/90 is taken as an adequate control. Attainment of target BP in treated hypertensives was similar to that reported from large trials. There is enormous scope for improving identification and follow-up of hypertensives using clinical computers and systematic models of care. The wide inter-practice variation in hypertension management requires further study.

Aged↗
PubMed1997

Connectivity and management of caribbean coral reefs

Surface current patterns were used to map dispersal routes of pelagic larvae from 18 coral reef sites in the Caribbean. The sites varied, both as sources and recipients of larvae, by an order of magnitude. It is likely that sites supplied copiously from "upstream" reef areas will be more resilient to recruitment overfishing, less susceptible to species loss, and less reliant on local management than places with little upstream reef. The mapping of connectivity patterns will enable the identification of beneficial management partnerships among nations and the design of networks of interdependent reserves.

Journal Article↗
PubMed2003

Structural differences in the enteric neural network in murine colon: impact on electrophysiology.

The enteric neural network in the proximal murine colon shows a regularly occurring hypoganglionic region, which is here characterized by using anatomical and electrophysiological techniques. Staining with NADPH diaphorase, methylene blue, and cuprolinic blue in standard whole mounts and three-dimensional gut preparations of the murine proximal colon consistently revealed two hypoganglionic areas surrounded by a dense clustering of enteric neurons. This irregularity in the ganglionic plexus was found to be present in mice of three different genetic backgrounds, as well as in rats. The lack of myenteric ganglia in these regions was associated with an absence of the longitudinal muscle layer, as shown in cross sections. Histochemical identification of interstitial cells of Cajal in Kit(W-lacZ/+) transgenic mice showed Kit-positive cells oriented parallel to both muscle layers of the colon. Kit-positive cells oriented parallel to the longitudinal muscle layers were absent in the hypoganglionic area described. Electrical field stimulation elicited TTX-sensitive inhibitory junction potentials (IJPs), which showed region-specific characteristics. The initial partly apamin-sensitive hyperpolarization was present in all parts of the murine colon, whereas a second sustained NG-nitro-L-arginine-sensitive hyperpolarization was absent in the cecum and decreased from the proximal to the distal colon. Dissecting the hypoganglionic area from the surrounding tissue abolished the otherwise normal inhibitory neurotransmission to the circular muscle (1.6 +/- 1.4 and 2.6 +/- 1.7 mV for the fast and slow component of IJP amplitude in the hypoganglionic area vs. 16.5 +/- 1.9 and 23.7 +/- 2.7 mV for the fast and slow component of IJP amplitude in the neuron-rich area, respectively, P < 0.01, n = 6), whereas dissection of an area of identical size with an intact myenteric network showed normal inhibitory neurotransmission, indicating that the hypoganglionic area receives essential functional neural input from the neuron-rich surrounding tissue. In summary, in the murine and rat proximal colon, a constant and distinct hypoganglionic region is described with important concomitant changes in local electrophysiology.

Animals↗
PubMed1982

The ultrastructure of radiation-induced endosteal myelofibrosis in the dog.

A rapidly developing, progressive form of endosteal myelofibrosis (MF) (with myeloid metaplasia) has been shown to occur at low frequency (approximately 4%) in dogs exposed continuously to low daily doses (10 R/day) of whole-body gamma irradiation. We report in this study the morphological details of the endosteal surface during both preclinical and clinical phases of developing MF by combination light microscopy and scanning/transmission electron microscopy. Pronounced alterations of the endosteum were observed and included: (1) during the early preclinical phases, a progressive time-dependent transition of the endosteal surface from predominantly resting to actively formative and resorptive states; and (2) during the late preclinical phase, aberrant autonomous osteogenic process(es) characterized by a marked reduction in the resorptive, osteoclast-associated endosteal areas occurring concomitantly with further increases in formative areas of the endosteum. Localized patches of overlapping, morphologically transformed endosteal cells (i.e., round-osteoblastic to branched-reticular shaped) were observed within the morphologically reactive, formative endosteum. Osteogenic-endosteal changes coincided with major restructuring of the hematopoietic parenchyma and supporting stromal network. We discuss the possibility that the early occurring endosteal changes are causally linked to normal reparative functions that operate during regenerative hematopoiesis following local and systemic injury. Based on morphological data collected during the late preclinical phase, we speculate that the mechanism of myelofibrosis induction involves the failure to terminate early osteogenic-dependent repair sequences.

Animals↗
PubMed1997

I want to live here for rest of my life. The challenge of case management for rural seniors.

The research on long-term care for seniors clearly demonstrates that efforts to integrate urban case management services with elderly people living in rural settings have not been successful. Presenting findings of the Rural Seniors Assisted Living Study conducted in northwestern Ontario, Canada, this article demonstrates the complexity of providing health and social services for seniors living in small rural communities, services that are often vastly different from those provided in urban communities. The article proposes a specialized Rural Case Management approach with rural elderly clients and identifies four intervention roles: providing direct service, consulting extensively with specialists of other disciplines, constructing and supporting natural helping networks, and resource management. The approach also requires that the rural case manager assume a leadership role at the community level in the development of services for seniors. Having a locally based case manager rather that a case manager who travels out to rural areas from an urban center is essential to the success of this rural case management approach. Finally, the article contends that rural case management differs from urban case management by requiring specialized knowledge, skills and educational programs.

Aged↗
PubMed2002

[Language activation in ischemic stroke and brain tumor: a PET study].

Disturbance of neurologic function in disorders of the central nervous system is expressed as altered activation pattern in functional networks after specific tasks, and can be studied by functional imaging modalities, e.g. positron emission tomography (PET). Language, a complex brain function is based on the interplay of a distributed network in which partial functions are executed in various centers and tasks are hierarchically organized according to their complexity. The specialization of different centers and the lateralization of integrative functions into the dominant (usually left) hemisphere is achieved by collateral and transcallosal inhibition of structures of lower order in the network. Patients with ischemic stroke often suffer from aphasia; the features and the prognosis of this disturbance is determined by the localization and the extent of the infarct in the dominant hemisphere. The preservation of the left superior temporal gyrus or its functional reintegration, respectively, is of utmost importance for the recovery of the deficits and for a satisfactory outcome. Reactivation of this region in repeated PET-activation studies were related to a favorable outcome, activation of other eloquent regions or of contralateral areas were accompanied by some improvements, but never indicated recovery of sufficient speech production. Symptoms develop slowly in patients with tumors in the left hemisphere, and the functional network can adapt to the lesion. In these patients a dislocation of areas activated during language tasks was observed, either to ipsilateral regions usually not involved or to contralateral homotopic areas. Aphasia was frequent in cases with activation shift to the subdominant hemisphere, and the right over left asymmetry in activation of the cerebellum was correlated to the severity of language impairment. The shift of dominance in activation could be reversed after surgical resection of the tumor leading to improved speech performance. The patterns of intrahemispheric as well as interhemispheric compensation may be explained by reduction of collateral inhibition of specific centers on other structures within the network (disinhibition): circumscript and/or slowly developing lesions disinhibit surrounding areas leading to increases and to displacements of activated centers; large morphological defects reduce the transcallosal inhibition leading to the activation of contralateral regions.

Adult↗
PubMed2005

Spatial distribution of osteocyte lacunae in equine radii and third metacarpals: considerations for cellular communication, microdamage detection and metabolism.

Osteocytes, which are embedded in bone matrix, are the most abundant cells in bone. Despite the ideal location of osteocytes to sense the local environment and influence bone remodeling, their functions, and the relative importance of these functions, remain controversial. In this study, we tested several hypotheses that address the possibilities that population densities of osteocyte lacunae (Ot.Lc.N/B.Ar) correlate with strain-, remodeling- or metabolism-related aspects of the local biomechanical environments of mid-third diaphyseal equine radii and third metacarpals from skeletally mature animals. Ot.Lc.N/B.Ar data, quantified in multiple cortical locations, were analyzed for possible correlations with (1) structural and material characteristics (e.g., cortical thickness, percent ash, secondary osteon population density, mean osteon cross-sectional area, and predominant collagen fiber orientation), (2) strain characteristics, including prevalent/predominant strain magnitude and mode (tension, compression, shear), (3) hypothesized strain-mode-related microdamage characteristics, which might be perceived by osteocyte 'operational' networks, and (4) variations in remodeling dynamics and/or metabolism (i.e. presumably higher in endocortical regions than in other transcortical locations). Results showed relatively uniform Ot.Lc.N/B.Ar between regions with highly non-uniform strain and strain-related environments and markedly heterogeneous structural and material organization. These results suggest that population densities of these cells are poorly correlated with mechanobiological characteristics, including local variations in metabolic rate and strain magnitude/mode. Although osteocytes hypothetically evolved both as strain sensors and fatigue damage sensors able to direct the removal of damage as needed, the mechanisms that govern the distribution of these cells remain unclear. The results of this study provide little or no evidence that the number of osteocyte lacunae has a functional role in mechanotransduction pathways that are typically considered in bone adaptation.

Animals↗
PubMed2003

8-oxoguanine lesioned B-DNA molecule complexed with repair enzyme hOGG1: a molecular dynamics study.

The molecular dynamics (MD) simulation of DNA mutagenic oxidative lesion, 7,8-dihydro-8-oxoguanine (8-oxoG), complexed with the repair enzyme, human oxoguanine glycosylase 1 (hOGG1), was performed for 1 nanosecond (ns) in order to describe the dynamical process of DNA-enzyme complex formation. After 900 picoseconds of MD the lesioned DNA and enzyme formed a complex that lasted until the end of the simulation at 1 ns. The complex was mainly represented by the overlapping van der Waals surfaces of DNA and enzyme molecules. The amino group of arginine 324 was located close to the phosphodiester bond of the nucleotide with 8-oxoG enabling chemical reactions between amino acid and lesion. The broken hydrogen bonds resulting in locally collapsed B-DNA structure were observed at the lesion site. The phosphodiester bond at C5' of 8-oxoG was displaced to the position close to the amino group of arginine 324. The water-mediated hydrogen bond network was formed in each contact area between DNA and enzyme, further enhancing the stability of the complex. In the background simulation of the identical molecular system with the native DNA, neither the complex nor the water- mediated hydrogen bond network was observed.

Algorithms↗
PubMed1998

Toward a new urban health model: moving beyond the safety net to save the safety net--resetting priorities for healthy communities.

Parkland Health and Hospital System has been successful by every measure of comparison among its peer institutions, yet it recognizes the imperative of adapting to changes in the regulatory, legislative, and market environments. Given its mandate and a desire to preserve its multiple missions and its partnerships with a highly rated medical school, the playing field for achieving robust survival is very uneven. This article describes the evolution of one of the best "sick care systems" in the United States into an integrated, excellent health care system for the 21st century. The problems faced by the safety net in many urban areas of this country are similar. Many problems are structural in nature and will, therefore, require structural solutions at the local, state, and national levels. Parkland will continue and will be needed for many years as the tertiary and quaternary center of a comprehensive service network made up also of a series of outreach Community Oriented Primary Care clinics and special populations projects. In addition, we hope to help create a community-oriented managed-care plan that encompasses the desire to work with both denominator and numerator populations in a real partnership with many other stake-holders.

Academic Medical Centers↗
PubMed2004

Models of MT and MST areas using wake-sleep algorithm.

We present two-layered neural network models with Q (> or =2)-states neurons for a system with middle temporal (MT) neurons and medial superior temporal (MST) neurons by using a wake-sleep algorithm proposed by Hinton et al.; we notice that the wake-sleep algorithm consists of local learning rules. We first investigate a model with binary neurons for response properties of the MST neurons to optical flows as for various types of motion. We next extend the model with binary neurons to a model with Q (> or =3)-states neurons and investigate the response properties of the MST neurons for various values of Q (> or =3). We obtain better response properties for the model with Q (> or =3)-states neurons than for the one with binary neurons.

Algorithms↗
PubMed1997

Increased expression of CD11b/CD18 on phagocytes in ischaemic disease: a bridge between inflammation and coagulation.

The aim of this study was to assess the expression of CD11b/CD18 integrin adhesion molecules on the phagocytes of patients with ischaemic diseases, and to evaluate the concentration of soluble adhesion molecules that are released from endothelium (sICAM-1) and from phagocytes (sL-selectin). A total of 370 patients were enrolled: 120 with coronary artery disease (CAD); 50 with peripheral artery occlusive disease (PAOD); and 200 control subjects with no clinical manifestations of ischaemic disease. CD11b/CD18 integrin was detected by flow cytometry, whereas sL-selectin and sICAM-1 concentrations were detected using a sandwich-type immunoassay. CD11b/CD18 integrin expression was found to be higher in the patients with ischaemic disease than in the control subjects (P < 0.001). The PAOD patients had higher values of CD11b/CD18 integrin than the CAD ones (P < 0.01). The concentration of soluble adhesion molecules did not show any significant differences within the three groups (P = NS). The high expression of CD11b/CD18 integrin in ischaemic disease patients may depend on the increased, but probably stable, cytokine network that has been demonstrated to occur in chronic ischaemic diseases: the difference observed between PAOD and CAD patients could be the consequence of higher inflammatory activation probably resulting from the greater extent of the atherosclerotic process in PAOD, or of the more localized ischaemic area in CAD patients. CD11b/CD18 can therefore be considered a marker of chronic phagocyte activation during ischaemic disease. On the other hand, sICAM and sL-selectin concentrations were found to be within the normal range; they have recently been considered as a marker for acute ischaemic events and acute inflammatory process activation. Our results confirm that in uncomplicated atherosclerosis no acute inflammatory process activation should occur.

Blood Coagulation↗
PubMed1999

Folkecology and commons management in the Maya Lowlands.

Three groups living off the same rainforest habitat manifest strikingly distinct behaviors, cognitions, and social relationships relative to the forest. Only the area's last native Maya reveal systematic awareness of ecological complexity involving animals, plants, and people and practices clearly favoring forest regeneration. Spanish-speaking immigrants prove closer to native Maya in thought, action, and social networking than do immigrant Maya. There is no overriding "local," "Indian," or "immigrant" relationship to the environment. Results indicate that exclusive concern with rational self-interest and institutional constraints do not sufficiently account for commons behavior and that cultural patterning of cognition and access to relevant information are significant predictors. Unlike traditional accounts of relations between culture, cognition, and behavior, the models offered are not synthetic interpretations of people's thoughts and behaviors but are emergent cultural patterns derived statistically from measurements of individual cognitions and behaviors.

Anthropology↗
PubMed1990

Scrotal septocutaneous island flap for the reconstruction of the urethral fistula.

We report the reconstruction of the urethral fistula using a scrotal septocutaneous island flap. A scrotal septocutaneous island flap is supplied by vascular networks in the scrotal septum area from both perineal arteries and posterior scrotal arteries. This flap is divided into two flaps, one for urethral lining and the other for the skin defect. We found it to be a simple, useful, and reliable alternative to other local flaps. However, hairless skin of the scrotum must be used for the urethral lining. The musculocutaneous flap is also reliable. However, use of the scrotal septocutaneous island flap can save the musculocutaneous flap for secondary procedures.

Humans↗
PubMed1990

Indigent health care plan for Tennessee.

The author describes the development of an Indigent Health Care Program for the State of Tennessee from the campaign pledge of the Governor, through the development of an Indigent Care Cabinet Council, to the development and enactment of appropriate legislation required to implement this program. The program deals with availability of health care services, accessibility to health care services and funding mechanisms. The backbone of the program is the involvement of the local community and the coordinating and networking of the existing private, community and state health care providers.

Community Health Centers↗
PubMed1995

Variability in choriocapillaris blood flow distribution.

PURPOSE: To investigate variability of choriocapillaris blood flow patterns. METHODS: After the intravenous injection of indocyanine green, angiograms were recorded at 30 images per second in rhesus monkey eyes using a fundus camera equipped with a pulsed laser diode light source, synchronized with a gated (5 msec), intensified charge-coupled device, or CCD, video camera. Images of choriocapillaris filling alone were extracted. Plastic corrosion casts were made of two of the monkey's choroidal vasculatures for subsequent scanning electron microscopy examination. RESULTS: Pulsed laser indocyanine green fluorescence excitation produced better definition of choriocapillaris filling than had been achieved using continuous illumination. No correlation was found between the choriocapillaris plexus architecture revealed by the plastic corrosion casts and the observed choriocapillaris lobular filling. Overall posterior pole choriocapillaris dye-filling patterns were relatively stable for periods of days, but they changed gradually for periods of weeks. Localized minor pattern changes occurred on a much shorter time scale. Choriocapillaris filling patterns were altered by acutely elevating intraocular pressure, by O2 and CO2 breathing, and by argon laser retinal photocoagulation of adjacent areas. CONCLUSIONS: Choriocapillaris filling patterns appear to be determined by the network of perfusion pressure gradients that exist among the interspersed feeding arterioles and draining venules connected to the choriocapillaris plexus. Changes in intraocular pressure and in blood PO2 and PCO2 levels can produce marked changes in the distribution of choriocapillaris blood flow. Retinal laser photocoagulation of adjacent fundus areas alters choriocapillaris blood flow to the extent that the altered flow might be an important factor in the beneficial results attributed to retinal laser treatment.

Animals↗