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PubMed1995

Vascular dynamics in isolated systolic arterial hypertension.

With a growing elderly population, the incidence of isolated systolic hypertension (ISH) has increased. This study characterizes dynamic vascular changes that occur with advanced age and with ISH. Fifty-five healthy individuals and seven with ISH were distributed in seven age groups from the second to the seventh decade. An index of aortic stiffness (delta P/delta V) was derived using a mercury sphygmomanometer to obtain pulse pressure, and ultrasonographic measurements were used to estimate aortic volumes applying the "cylinder formula." The mathematic derivation of this formula is explained in detail. Pulse pressure showed no significant change with age, but showed a significant increase with ISH. A decrease in volume change from systole to diastole was found with advanced age. Normotensive subjects aged 65 +/- 2 years had a 2.6-fold increase in aortic stiffness compared with young individuals. Elderly patients with ISH had a 7-fold increase in aortic stiffness compared with Group 1 (15 +/- 2 years) (p < 0.001) and a 2.7-fold increase compared with Group 6 (normotensive subjects aged 65 +/- 2 years). A strong correlation between systolic pressure and arterial stiffness was observed (r = 0.953) (p < 0.001). The proposed stiffness index was compared with the one described by Hirai, obtaining a high correlation, that is, r = 0.989 (p < 0.001). When compared with Stefanadis' index of distensibility, our index showed a correlation of r = 0.932 (p < 0.003). It is concluded that while systolic pressure is a main determinant of arterial stiffness, the delta P/delta V is a more sensitive method to estimate dynamic changes in elastic arteries such as the aorta.

Adolescent↗
PubMed1997

Transients, metastability, and neuronal dynamics.

This paper is about neuronal dynamics and how their special complexity can be understood in terms of nonlinear dynamics. There are many aspects of neuronal interactions and connectivity that engender the complexity of brain dynamics. In this paper we consider (i) the nature of this complexity and (ii) how it depends on connections between neuronal systems (e.g., neuronal populations or cortical areas). The main conclusion is that simulated neural systems show complex behaviors, reminiscent of neuronal dynamics, when these extrinsic connections are sparse. The patterns of activity that obtain, under these conditions, show a rich form of intermittency with the recurrent and self-limiting expression of stereotyped transient-like dynamics. Despite the fact that these dynamics conform to a single (complex) attractor this metastability gives the illusion of a dynamically changing attractor manifold (i.e., a changing surface upon which the dynamics unfold). This metastability is characterized using a measure that is based on the entropy of the time series' spectral density.

Animals↗
PubMed1993

Dynamic changes in the receptive field properties of spinal cord neurons with ankle input in rats with chronic unilateral inflammation in the ankle region.

The aim of this study was to determine the discharge and receptive field properties of spinal cord neurons with ankle input in spinal segments L4-6 in the rat, both under control conditions and during the course of an adjuvant-induced unilateral inflammation in the ankle. The extent of receptive fields in the skin and deep tissue was assessed using brush, pinch and compression stimuli. Neurons were categorized as nociceptive-specific or wide-dynamic-range neurons on the basis of their response thresholds and responses to suprathreshold stimuli. At all stages of inflammation (2, 6, 13 and 20 days post inoculation) the population of neurons with ankle input showed differences from the population of neurons with ankle input in control rats. There was a reduction in the number of neurons that appeared as nociceptive specific and a concomitant increase in the number of neurons showing a wide-dynamic-range response profile. The receptive fields of the neurons with ankle input were markedly larger in rats with inflammation in the ankle region and mainly spread proximally on the ipsilateral hindlimb and also to the abdomen and tail in some cases. There was also an increase in the number of neurons with contralateral excitatory inputs. The mechanical thresholds at the ankle joint and proximal parts of the ipsilateral hindlimb were less in arthritic rats than in controls. The proportion of spontaneously active neurons was also increased in rats during the initial and later stages of inflammation, although there was no significant increase in the mean spontaneous discharge frequency. These data show that there are long-term changes in the receptive field and response properties of neurons in intact rats with chronic unilateral adjuvant-induced inflammation similar to those described previously in spinal cats with acute inflammation (Neugebauer and Schaible 1990). It is presumed that similar afferent and spinal mechanisms are at work under acute and chronic inflammatory conditions which produce hyperexcitability in spinal neurons with joint input.

Animals↗
PubMed1992

Serum gonadotropins and gonadal steroids associated with ovulation and egg production in sea turtles.

Changes in serum concentrations of gonadotropins and gonadal steroids during the periovulatory period were monitored in green, Chelonia mydas, and loggerhead, Caretta caretta, sea turtles. Turtles were from natural populations that nest on a coral island on the Great Barrier Reef. After nesting, each turtle was transferred to a holding tank and held for a maximum of 8 days. A time series of blood samples was obtained from each of five sea turtles (three C. mydas and two C. caretta) starting immediately after nesting and then at approximately 12-hr intervals until the time of release. Prior to release back into the ocean, each turtle was examined by laparoscopy to verify that ovulation had occurred. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (PRO), and testosterone (T) in both species exhibited significant changes during this period. Surges of FSH, LH, and PRO were evident within approximately 20 to 50 hr after each turtle had nested. The significant change in FSH concentration during the periovulatory period is the first such report for a reptile. Coincident with maximal concentrations of FSH, LH, and PRO was a decline in T concentrations in both species. Estradiol-17 beta concentrations were near or below assay sensitivity in the C. mydas, whereas those in the C. caretta were detectable but exhibited no significant changes. The dynamic changes in FSH, LH, PRO, and T concentrations are consistent with the hypothesis that these hormones facilitate specific physiological events during ovulation and egg production.

Animals↗
PubMed1989

Age-related changes in naive and memory CD4+ T cells in healthy human children.

Subsets of CD4+ T cells originally identified functionally as suppressor-inducer and helper-inducer populations have recently been reinterpreted as naive and memory maturational states. The subsets can be identified by the surface expression of CD45R and CDw29, respectively. Using two-color flow cytometric analysis, we measured these CD4+ T cell subsets in two samples of cord blood and in 26 healthy children between the ages of 1 and 19 years. As has been reported by others, we observed that the majority of CD4+ T cells in cord blood consist predominantly of the CD45R+ subset. With aging we could demonstrate a gradual acquisition of CDw29+, CD4+ T cells and a concomitant gradual decrease in the percentage of CD45R+, CD4+ T cells. These age-related changes are consistent with the concept of naive (CD45R+) and memory (CDw29+) subsets. Further, because of the dynamic changes, their utilization as prognostic indicators in immunologic disease states cannot be applied to children in the same manner as adults.

Adolescent↗
PubMed1986

Aminophylline exposure alters mouse bone marrow-derived mast cell adenosine responsiveness.

Aminophylline-treated mouse bone marrow-derived mast cells exhibit a hyperresponsiveness to adenosine addition (10(-6) to 10(-4) mol/L) at the time of secretagogue challenge coincident with an up regulation of adenosine receptor numbers. This effect on beta-hexosaminidase release is maximal at 100 mumol/L of aminophylline, evident after 5 days of aminophylline exposure, and reversed by 6 days after washing. Neither radiolabeled arachidonic acid nor leukotriene C4 release in the absence or presence of adenosine was altered by aminophylline treatment. Although cAMP levels were dynamically changed by adenosine or secretagogue, these changes were not different in the two cell populations; resting and challenged mast cell adenosine levels were similarly unaffected by aminophylline. The long-term action of aminophylline on mouse bone marrow-derived mast cells appears to be primarily on adenosine receptors and thereby on preformed mediators, and this action may have some importance in the pathophysiology and treatment of asthma.

Adenosine↗
PubMed1990

Influence of development and aging on nicotinic receptor subtypes in rodent brain.

The influence of development and aging on nicotinic receptor subtypes in rodent brain was investigated. 3H-nicotine and 3H-acetylcholine (3H-ACh) were used as receptor ligands. Specific binding sites for 3H-nicotine and 3H-ACh were detected in mouse brain during the late prenatal period. A drop in the number of 3H-nicotine and 3H-ACh binding sites was measured shortly after birth. The 3H-nicotine and 3H-ACh binding sites showed different time courses during prenatal development. Competition experiments using unlabelled (-)nicotine and 3H-nicotine revealed one population of high affinity nicotinic binding sites in the cortex of 1-day and 5-day-old mice whereas both a set of high and low affinity binding sites were found in adult mice. The proportion of cortical high and low affinity nicotinic binding sites did not change with aging although the absolute amount of high affinity nicotinic binding sites decreased. The 3H-nicotine binding showed different temperature dependence in rat brain of different ages. The results illustrate dynamic changes in nicotinic receptor properties during life span of rodents.

Aging↗
PubMed2026

Proteomic analysis reveals early pathological defects in corticospinal motor neurons of a spastin model of hereditary spastic paraplegia, which are improved by NU-9 treatment.

Upper motor neuron (UMN) degeneration is a characteristic feature of hereditary spastic paraplegia (HSP), a genetically heterogeneous heritable neurodegenerative disorder resulting from mutations in over ninety genes. The mutations in the SPAST gene, which encodes the microtubule-severing protein spastin, are responsible for about 40% of all HSP cases. To date, the cellular and molecular mechanisms linking mutant spastin protein to UMN vulnerability in HSP patients remain unknown and there are no disease modifying therapies. To address this knowledge gap, we isolated pure populations of corticospinal motor neurons (CSMN; a.k.a. UMN in mice) from SPASTC448Y-UeGFP reporter mice at two pre-symptomatic time points and performed bottom-up proteomic analyses to reveal changes in their proteome that informs the underlying causes of their initial vulnerability. We find dynamic changes in their proteome and that limitations with cytoarchitectural integrity and stability of key organelles contribute to their neuronal vulnerability. Since the compound NU-9 was shown to improve similar cellular problems in CSMN that are diseased due to misfolded SOD1 toxicity and TDP-43 pathology, we further investigated its effect on the well-established pathological features of HSP that are recapitulated in the SPASTC448Y mice. We find that NU-9 treatment (100&#xa0;mg/kg, for 100&#xa0;days) significantly prevented degeneration of corticospinal axons, restored the integrity of mitochondria and endoplasmic reticulum, and reduced the presence of electron-dense accumulations in the CSMN of SPASTC448Y mice.

Animals↗
PubMed1988

On the occurrence of three-center hydrogen bonds in cyclodextrins in crystalline form and in aqueous solution: comparison of neutron diffraction and molecular dynamics results.

Three-center (bifurcated) hydrogen bonds may play a role by serving as an intermediate state between different dynamically changing hydrogen bonding patterns. Hydrogen bonding configurations can be studied experimentally by neutron diffraction and theoretically by computer simulation techniques. Here, both methods are used to analyse the occurrence of three-center hydrogen bonds in crystals of cyclodextrins. Almost all experimentally observed three-center hydrogen bonds in the crystal are reproduced in the molecular dynamics (MD) simulations, even as far as the detailed asymmetric geometry is concerned. On the basis of this result a MD simulation of cyclodextrin in aqueous solution is searched for the occurrence of three-center hydrogen bonds. Significant differences are found. In solution more different three-center hydrogen bonds per alpha-cyclodextrin molecule are observed than in the crystal but the population (existence as percent of the simulation period) of each three-center hydrogen bond is lower in solution than in crystal. These may indeed serve as intermediate states in the process of changing one hydrogen bonding pattern into another.

Chemical Phenomena↗
PubMed2025

Dynamic changes in chromosome and nuclear architecture during maturation of normal and ALS C9orf72 motor neurons.

We have investigated changes in chromosome conformation, nuclear organization, and transcription during differentiation and maturation of control and mutant motor neurons harboring hexanucleotide expansions in the C9orf72 gene that cause amyotrophic lateral sclerosis (ALS). Using an in vitro reprogramming, differentiation and neural maturation protocol, we obtained highly purified populations of post-mitotic motor neurons for both normal and diseased cells. As expected, as fibroblasts are reprogrammed into iPSCs, and as iPSCs differentiate into motor neurons, chromatin accessibility, chromosome conformation, and nuclear organization change along with large-scale alterations in transcriptional profiles. We find that the transcriptome changes extensively during the first three weeks of post-mitotic neuronal maturation, with thousands of genes changing expression, but then is relatively stable for the next three weeks. In contrast, chromosome conformation and nuclear organization continue to change over the entire 6-week maturation period: chromosome territoriality increases, long-range interactions along chromosomes decrease, compartmentalization strength increases, and centromeres and telomeres increasingly cluster. In motor neurons derived from ALS patients such changes in chromosome conformation were much reduced. Chromatin accessibility changes also showed delayed maturation. The transcriptome in these cells matured relatively normally but with notable changes in expression of genes involved in lipid, sterol and mitochondrial function. We conclude that neural maturation is associated with large scale post-mitotic changes in gene expression, chromosome conformation and nuclear organization, and that these processes are defective in motor neurons derived from ALS patients carrying C9orf72 hexanucleotide repeat expansions.

Journal Article↗
PubMed1985

Short-term dynamic psychotherapy. V. Global assessment scale as an instrument for description and measurement of changes for 33 neurotic patients.

Global assessment scale (GAS) has not been tested out on a group of neurotic out-patients earlier. The patients in this study were selected for short-term dynamic psychotherapy by defined selection criteria and were thus a fairly homogeneous group of patients. It could be demonstrated that GAS could be used as a supplement for describing patient characteristics both at the start of treatment and at the 5-year follow-up. GAS could further be used for measuring change for this patient population after short-term dynamic psychotherapy. GAS could not be used as a predictor for dynamic change at the 5-year follow-up.

Adult↗
PubMed1999

Lack of sex difference in cerebrospinal fluid (CSF) leptin levels and contribution of CSF/plasma ratios to variations in body mass index in children.

In adults, leptin seems to cross the blood-brain barrier by a saturable transporter. This may contribute to the development of obesity. The present study in healthy children investigates leptin levels in plasma and cerebrospinal fluid (CSF) in relation to body constitution. This prospective study analyzed leptin levels in plasma and CSF samples (stored at -80 C) of patients without CNS infection or blood-brain barrier dysfunction. Inclusion criteria included temperature less than 38.5 C, C-reactive protein levels below 10 mg/L, CSF leukocyte levels less than 10(7)/L, no need for neurosurgical or oncological treatment, and no history of trauma. Four groups were designated according to body mass index. Sixty-five children (28 girls and 37 boys) entered the study. Plasma leptin (median) was 7.4 in girls and 2.6 ng/mL in boys., CSF leptin was 0.273 and 0.204 ng/mL, respectively, leading to CSF/plasma ratios of 0.045 and 0.071, respectively. Ratios were clearly dependent on body mass index percentiles (r = -0.484; P < 0.01, significant differences between groups by ANOVA). Median plasma leptin levels in the 4 groups (body mass index, <10th, 10th-50th, 50th-90th, and >90th percentile) were 2.0, 2.3, 4.1, and 8.8 ng/mL; CSF/plasma ratios were inversely related: 8.2%, 7.6%, 5.5% and 3.6%. In healthy children, CSF leptin levels account for approximately 5% of plasma levels. CSF/plasma ratios in girls are lower than those in boys, explaining why calorie intake and energy expenditure are not grossly different despite large differences in circulating plasma leptin concentrations. CSF/plasma ratios of lean children are higher than those in obese children. The dynamic changes in the CSF/plasma ratios are more pronounced in lean children, i.e. the nonlinear transport characteristics of the leptin system amplifies the information about changes in body energy stores in this population, indicating that leptin is part of a mechanism to protect the body from critical weight loss rather than to avoid obesity.

Adolescent↗
PubMed1992

Role of the health professional in ending the tobacco pandemic: clinic, classroom, and community.

Physicians and other health professionals have become complacent about the tobacco pandemic, because there is a mistaken belief that the war on smoking has been won. In reality, the survival from lung cancer is little better than it was 30 years ago, and cigarettes have become the most advertised and promoted product in society. The prevalence of overall smoking in the United States has declined by only 0.5%/y during the past decade. Among certain US minority populations, the decline has been far less or nonexistent. Traditional efforts to control the tobacco pandemic have been reactive and static, whereby government agencies, schools, and health professionals provide the public with generic information about the adverse health effects of smoking. As a result of these efforts, it is assumed that individuals will act to change their behavior. In contrast, the tobacco industry is proactive and dynamic, changing its brand-name strategies through advertising and promotion. To more effectively combat tobacco use, health officials need to move beyond patient education and adopt a more active model that includes clinic-based, school-based, and community-based tobacco-control strategies. Use of humorous, satirical images as part of paid counteradvertising campaigns and proactive health education curricula should be part of a concerted effort to end the tobacco pandemic and limit the promotional influence of tobacco companies.

Consumer Advocacy↗
PubMed1991

[Various results of the study of medico-biological aspects of alcoholism in Siberia and Far East].

To study the dynamic changes in alcohol abuse, a new methodological approach has been developed which implies staged realization. Stage one was aimed at the search for integral clinical-dynamic characteristics as well as social and psychological properties to make identification of the clinical phenotype reliable. Stage II--at introduction of integral constitution-morphology indicators representative of the disease predisposition-stability. The analysis of medicosocial characteristics for the last 8 years has been performed at Stage III. Calcium homeostasis and related hormones and enzymes were evaluated at Stage IV. The data obtained permitted identification of a complex of structural manifestations underlying alcohol embryopathy of the brain.

Alcoholism↗
PubMed1990

[Myosin ATPase activity in somatic muscle fibers in different degree of pH of the pre-incubation medium].

The problem on presence of muscle fibers (MF) types is an actual one, since it is a prerequisite to forecasting certain changes in MF under different conditions. The aim of the investigation has been to find out whether independent groups of MF exist or whether they react as a whole population to gradual changes in pH of the preincubational medium, when dynamic changes in m-ATPhase activity are studied. In serial transversal cryostate slices 10 mcm thick m-ATPhase activity has been defined in MF at preincubation of the slices in media having various pH. The experiment has had three series. In the I--the ventral denticulate muscle with universal biomechanical properties has been investigated; preincubation has been carried out in media having pH from 3.0 up to 11.0 with the intervals 0.5 pH. In the II--besides the muscle mentioned the fast brachial muscle and the force triceps muscle have been studied; preincubation has been performed only at pH 9.5, since in the I series two dissociated groups of MF have been distinguished. In the III series, at studying the same three muscles m-ATPhase activity has been detailed with their preincubation at pH from 3.8 up to 4.5 with the interval 0.1. The m-ATPase activity begins to manifest in various MF at pH of the preincubational medium within the limits of 3.8-4.2. A gradual increase in amount of MF that are revealing, as pH is gradually increasing, evidences most likely against independence of separate groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. III. Morphometric assessment of the dynamic changes in post-capillary venules as regulatory elements of lymphocyte recirculation in tumor-draining lymph nodes.

To evaluate the dynamics of lymphocyte recirculation in tumor-bearing mice, the post-capillary venules (PCV) were subjected to quantitative measurements in the regional (RLN) and nonregional (NRLN) lymph nodes during the progression of P815X2 mastocytoma in syngeneic DBA/2 mice. Mice were sacrificed at two-day intervals, and RLNs and NRLNs were analysed for their content of B- and T-lymphocytes and their subsets, demonstrated by immunoperoxidase technique using monoclonal antibodies; Anti-Thy 1.2 (T cells), Anti-Lyt 1 (T-helper cells), Anti-Lyt 2 (T-suppressor cells), and Anti-I-Ad (B cell) antigens, separately in the B- and T-cell compartments. In the PCVs, migration index (MI) and endothelial height (Hend) were measured. There was a biphasic elevation of MI in the RLNs, as compared with only a late rise in the NRLNs, reaching the peak (1.54) on day 14. In RLNs, there was a sharp reduction in Hend starting from the values (6.37 microns) on day 2, down to 4.79 microns on day 8. This is followed by rapid elevation close to the second-day values, e.g. 6.07 on day 10. The changes in MI paralleled the early influx of B cells, as evidenced by the decrease of Thy 1.2+/I-Ad+ cell ratio and a late recruitment of T cells as indicated by the elevation of that ratio as well as the Hend values in both the RLNs and NRLNs. The present experiment shows that morphology of PCVs in the RLNs and in NRLNs of P815X2-bearing mice is subjected to alterations reflecting the dynamics of lymphocyte recruitment into these organs. When combined with lymphocyte subset enumeration using monoclonal antibodies, the quantitative analysis of the PCVs permits predictions to be made on the recirculatory activity of these cell populations during the tumor progression.

Animals↗
PubMed1996

Persistence of dominant T cell clones in synovial tissues during rheumatoid arthritis.

In a previous study, we showed that the T cell repertoire is biased in the synovial membrane (SM) compared with peripheral blood during rheumatoid arthritis (RA). The same bias was observed in different joints from the same patient and seems to be the same over time. To discover whether this bias was due to expansion of a clonal subset resulting from activation by conventional Ag(s) or to polygonal stimulation by superantigen(s), we sequenced more than 650 TCRBV-D-J junctional regions from freshly isolated SM and peripheral blood of two DR4-RA patients. From each patient, two SM were obtained on the same day, and a third was obtained later. Several dominant clones were found in SM but not in peripheral blood. Some of them were found only at the first time point in anatomically different SM, the majority persisted over time, and others were detected only at the second time point. Analysis of the complementarity-determining region 3 (CDR3) showed a bias in TCRBD and amino acid usage. Valine, encoded by randomly inserted N nucleotides, was used by 45% of dominant clones compared with 18% in the control population (p less than 0.001). In addition, GXXG and TSG motifs were frequently observed in the CDR3 of these dominant clones. These data indicate a dynamic TCR selection process during the perpetuation phase of RA. The dynamic changes of dominant clones also suggest a determinant spreading mechanism during RA.

Amino Acid Sequence↗
PubMed1996

Seasonal population dynamics of Halipegus occidualis and Halipegus eccentricus (Digenea:Hemiuridae) in their amphibian host, Rana clamitans.

The seasonal population dynamics of Halipegus occidualis and Halipegus eccentricus (Hemiuridae) in their amphibian host, the green frog (Rana clamitans), were examined for 3 yr (weekly, April through October). Frogs were caught, marked, and examined for H. occidualis and H. eccentricus, both of which occur as immatures and adults in the buccal cavity. Frogs were then released and allowed to continue natural recruitment and loss of the parasites. It was thus possible to monitor individual infrapopulations over successive time periods. One-hundred and forty-nine frogs were caught and released, with a total of 328 observations. Overall, the levels of both parasites among male and female frogs were similar, as were levels of infection among adult and juvenile hosts. There was, however, no correlation between the total number of H. occidualis and the body size (snout-vent length) of R. clamitans. In contrast, there was a significant correlation between the total number of H. eccentricus and frog size. Recruitment of both species began in May, peaked in June/July, and ended in July (H. eccentricus) or August (H. occidualis). In general, both the prevalence and relative density of H. occidualis was greater than that of H. eccentricus and may be related to space constraints in the buccal cavity of R. clamitans. Adults of both species were observed from April through October. Following increases in parasite recruitment, infrapopulation sizes declined in September 1992 and in August of 1993 and 1994. Examination of variance to mean ratios indicated that both species were overdispersed in the frogs. Large declines in the variance to mean ratios for H. occidualis after periods of greatest recruitment are most likely associated with the loss of larger infrapopulations, suggesting that there may be density-dependent regulation of infrapopulation size. By monitoring individual hosts using the mark-release-recapture protocol, dynamic changes in parasite infrapopulations were observed, e.g., there were losses of immature worms and rapid changes in infrapopulation sizes, observations that would not be made with typical host-parasite systems.

Animals↗