DAP

Материал из hpluswiki
Перейти к навигации Перейти к поиску

Death-associated protein 1 (DAP-1) [DAP1]

Publications[править]

Examining changes in the equity of physician distribution in Japan: a specialty-specific longitudinal study.

In this longitudinal study, we examined changes in the geographical distribution of physicians in Japan from 2000 to 2014 by clinical specialty with adjustments for healthcare demand based on population structure. The Japanese population was adjusted for healthcare demand using health expenditure per capita stratified by age and sex. The numbers of physicians per 100 000 demand-adjusted population (DAP) in 2000 and 2014 were calculated for subprefectural regions known as secondary medical areas. Disparities in the geographical distribution of physicians for each specialty were assessed using Gini coefficients. A subgroup analysis was conducted by dividing the regions into four groups according to urban-rural classification and initial physician supply. Over the study period, the number of physicians per 100 000 DAP decreased in all specialties assessed (internal medicine: -6.9%, surgery: -26.0%, orthopaedics: -2.1%, obstetrics/gynaecology (per female population): -17.5%) except paediatrics ( 33.3%) and anaesthesiology ( 21.1%). No reductions in geographical disparity were observed in any of the specialties assessed. Geographical disparity increased substantially in internal medicine, surgery and obstetrics and gynaecology(OB/GYN). Rural areas with lower initial physician supply experienced the highest decreases in physicians per 100 000 DAP for all specialties assessed except paediatrics and anaesthesiology. In contrast, urban areas with lower initial physician supply experienced the lowest decreases in physicians per 100 000 DAP in internal medicine, surgery, orthopaedics and OB/GYN, but the highest increase in anaesthesiology. Between 2000 and 2014, the number of physicians per 100 000 DAP in Japan decreased in all specialties assessed except paediatrics and anaesthesiology. There is also a growing urban-rural disparity in physician supply in all specialties assessed except paediatrics. Additional measures may be needed to resolve these issues and improve physician distribution in Japan.

MeSH Terms

  • Female
  • Health Workforce
  • Humans
  • Japan
  • Longitudinal Studies
  • Male
  • Medicine
  • Physicians
  • Rural Health Services
  • Rural Population
  • Urban Population

Keywords

  • aging
  • inequity
  • japan
  • physician


Evaluation of organ and effective doses during paediatric barium meal examinations using PCXMC 2.0 Monte Carlo code.

Radiation protection and estimation of the radiological risk in paediatric radiology is essential due to children's significant radiosensitivity and their greater overall health risk. The purpose of this study was to estimate the organ and effective doses of paediatric patients undergoing barium meal (BM) examinations and also to evaluate the assessment of radiation Risk of Exposure Induced cancer Death (REID) to paediatric patients undergoing BM examinations. During the BM studies, fluoroscopy and multiple radiographs are involved. Since direct measurements of the dose in each organ are very difficult if possible at all, clinical measurements of dose-area products (DAPs) and the PCXMC 2.0 Monte Carlo code were involved. In clinical measurements, DAPs were assessed during examination of 51 patients undergoing BM examinations, separated almost equally in three age categories, neonatal, 1- and 5-y old. Organs receiving the highest amounts of radiation during BM examinations were as follows: the stomach (10.4, 10.2 and 11.1 mGy), the gall bladder (7.1, 5.8 and 5.2 mGy) and the spleen (7.5, 8.2 and 4.3 mGy). The three values in the brackets correspond to neonatal, 1- and 5-y-old patients, respectively. For all ages, the main contributors to the total organ and effective doses are the fluoroscopy projections. The average DAP values and absorbed doses to patient were higher for the left lateral projections. The REID was calculated for boys (4.8 × 10(-2), 3.0 × 10(-2) and 2.0 × 10(-2) %) for neonatal, 1- and 5-y old patients, respectively. The corresponding values for girl patients were calculated (12.1 × 10(-2), 5.5 × 10(-2) and 3.4 × 10(-2) %).

MeSH Terms

  • Absorption, Radiation
  • Administration, Oral
  • Aging
  • Barium
  • Child, Preschool
  • Computer Simulation
  • Contrast Media
  • Fluoroscopy
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Models, Statistical
  • Monte Carlo Method
  • Organ Specificity
  • Radiation Dosage
  • Software
  • Viscera
  • Whole-Body Counting


Relationship between identity and attitude toward death in Japanese senior citizens.

This study aimed to clarify the relationship between identity development stages and attitudes towards death among Japanese senior citizens. The subjects were recruited from among approximately 500 students attending educational courses for senior citizens in Prefecture A. We collected the data by using the questionnaire and interview. The contents of questionnaire were Erikson Psychosocial Stage Inventory (EPSI) and Death Attitude Profile-Revised (DAP-R). In the interview, we represented the four developmental stages, and asked the questions from birth to the present. The collection rate was 85.4% (427 subjects). And 10 subjects participated in the interview. In relation to correlations between the EPSI sub-factors and the DAP-R subscales, there were moderately strong, negative correlations between "Integrity" and "Fear of death" and between "Integrity" and "Avoidance of death". In relation to the subjects' reflections on their lives, the following four categories were extracted: [Trust relationships with others], [Self-confidence regarding my own efforts], [Wanting to contribute to society], and [Let things be as they are]. These results suggested that the accomplishment of "Integrity", which is the developmental task in the maturity stage, leads to the attitude of accepting one's whole life. Further, we have clarified that "Integrity" promotes the acceptance of death.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Asian Continental Ancestry Group
  • Attitude to Death
  • Data Collection
  • Ego
  • Female
  • Humans
  • Interpersonal Relations
  • Interviews as Topic
  • Male
  • Middle Aged
  • Psychology
  • Self Concept
  • Social Identification
  • Surveys and Questionnaires
  • Trust


Flufenamic acid modulates multiple currents in gonadotropin-releasing hormone neurons.

Reproduction in mammals is dependent upon the appropriate neurosecretion of gonadotropin-releasing hormone (GnRH), yet the endogenous generation of activity underlying GnRH secretion remains poorly understood. We have demonstrated that the depolarizing afterpotential (DAP), which modulates bursting activity, is reduced in isolated GnRH neurons from aged animals. Calcium-activated non-specific cation (CAN) channels contribute to the DAP in other vertebrate neurosecretory cells. We used the CAN channel blocker flufenamic acid (FFA) to examine the contribution of CAN channels to the DAP in GnRH neurons during aging. Recordings were performed on isolated fluorescent GnRH neurons from young, middle-aged and aged female mice. Flufenamic acid inhibited spontaneous activity, but significantly increased the DAP in neurons from young and middle-aged animals. Apamin did not significantly potentiate the DAP, but did reduce the effects of FFA, suggesting that the increased DAP is partially due to blockade of apamin-sensitive SK channels. Flufenamic acid increased the current underlying the DAP (I(ADP)) and decreased the preceding fast outward current (I(OUT)) at all ages. These current responses were not affected by apamin, but TEA evoked similar changes. Thus, a potassium current, likely mediated through BK channels, contributes to the fast AHP and appears to offset the DAP; this current is sensitive to FFA, but insensitive to age. The effect of FFA on the DAP, but not I(ADP), is diminished in aged animals, possibly reflecting an age-related modulation of the apamin-sensitive SK channel. Future studies will examine the expression of SK channels during the aging process in GnRH neurons.

MeSH Terms

  • Action Potentials
  • Age Factors
  • Aging
  • Analysis of Variance
  • Animals
  • Anti-Inflammatory Agents
  • Brain
  • Female
  • Flufenamic Acid
  • Gonadotropin-Releasing Hormone
  • Green Fluorescent Proteins
  • Humans
  • Mice
  • Mice, Transgenic
  • Neurons
  • Ovariectomy
  • Patch-Clamp Techniques
  • Potassium Channel Blockers
  • Reaction Time
  • Sodium Channel Blockers
  • Tetraethylammonium
  • Tetrodotoxin

Keywords

  • FFA
  • GnRH
  • aging
  • calcium-activated non-specific cation channels
  • potassium channels


Developmental changes in the germinability, desiccation tolerance, hardseededness, and longevity of individual seeds of Trifolium ambiguum.

Using two parental clones of outcrossing Trifolium ambiguum as a potential model system, we examined how during seed development the maternal parent, number of seeds per pod, seed position within the pod, and pod position within the inflorescence influenced individual seed fresh weight, dry weight, water content, germinability, desiccation tolerance, hardseededness, and subsequent longevity of individual seeds. Near simultaneous, manual reciprocal crosses were carried out between clonal lines for two experiments. Infructescences were harvested at intervals during seed development. Each individual seed was weighed and then used to determine dry weight or one of the physiological behaviour traits. Whilst population mass maturity was reached at 33-36 days after pollination (DAP), seed-to-seed variation in maximum seed dry weight, when it was achieved, and when maturation drying commenced, was considerable. Individual seeds acquired germinability between 14 and 44 DAP, desiccation tolerance between 30 and 40 DAP, and the capability to become hardseeded between 30 and 47 DAP. The time for viability to fall to 50 % (p(50)) at 60 % relative humidity and 45 degrees C increased between 36 and 56 DAP, when the seed coats of most individuals had become dark orange, but declined thereafter. Individual seed f. wt at harvest did not correlate with air-dry storage survival period. Analysing survival data for cohorts of seeds reduced the standard deviation of the normal distribution of seed deaths in time, but no sub-population showed complete uniformity of survival period. Variation in individual seed behaviours within a developing population is inherent and inevitable. In this outbreeder, there is significant variation in seed longevity which appears dependent on embryo genotype with little effect of maternal genotype or architectural factors.

MeSH Terms

  • Adaptation, Physiological
  • Cell Survival
  • Coffea
  • Desiccation
  • Electron Spin Resonance Spectroscopy
  • Longevity
  • Seeds
  • Temperature
  • Trifolium


MTHFR 677T carrier influences the methylation status of H. pylori-infected gastric mucosa in older subjects.

DNA methylation is one of the major events in the early process of gastric carcinogenesis and it also occurs in non-neoplastic gastric mucosa. MTHFR plays a central role in biotransformation of folate to form S-adenosylmethionine, the universal methyl donor in cells and affects DNA methylation status. We investigated the association between common functional polymorphism of MTHFR C677T and DNA methylation status in H. pylori-infected non-neoplastic gastric mucosa. For 99 gastric mucosa samples from H. pylori positive non-cancer subjects, we assessed the association between MTHFR C677T genetic polymorphism and promoter methylation status of the four candidate promoters (p14, p16, DAP-kinase, and CDH1). In most all of the subjects, weak correlation was found between the p16 promoter methylation and MTHFR 677T carriers (age, sex-adjusted OR = 2.57, P = 0.053). When subjects were divided into two groups according to age, the MTHFR T carrier held a significantly higher risk of p16 promoter methylation, especially in 66 years or older generation (sex-adjusted OR = 14.28, P = 0.02). In addition, mean number of methylated CpG cites were significantly higher in T carrier than CC genotype in the same generation (P = 0.0418). Our data suggest that MTHFR 677T carrier influences the risk of DNA methylation in gastric mucosa in the long-term outcome of the H. pylori infection.

MeSH Terms

  • Aged
  • Aging
  • Apoptosis Regulatory Proteins
  • Cadherins
  • Calcium-Calmodulin-Dependent Protein Kinases
  • CpG Islands
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA Methylation
  • Death-Associated Protein Kinases
  • Female
  • Gastric Mucosa
  • Genotype
  • Helicobacter Infections
  • Helicobacter pylori
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Middle Aged
  • Promoter Regions, Genetic
  • Tumor Suppressor Protein p14ARF


Effects of dog-appeasing pheromones on anxiety and fear in puppies during training and on long-term socialization.

To evaluate the effectiveness of dog-appeasing pheromone (DAP) in reducing fear and anxiety in puppies and its effects on training and socialization. Randomized, controlled clinical trial. ANIMALS-45 puppies between 12 to 15 weeks of age at the time of inclusion. Puppies enrolled in puppy classes were randomly allocated to 1 of 4 groups: 2 large-breed groups (1 DAP and 1 placebo group) and 2 small-breed groups (1 DAP and 1 placebo group). The investigator, trainers, and owners were unaware of treatment allocation throughout the study. Classes lasted 8 weeks, and owners were asked to complete a questionnaire before the first lesson and at the end of each lesson thereafter. Data collected included amount of learning and degrees of fear and anxiety for each puppy. Follow-up telephone surveys of owners to obtain information on subsequent socialization of puppies were performed at 1, 3, 6, and 12 months after the classes ended. Dogs in DAP and placebo groups were significantly different with respect to degrees of fear and anxiety; longer and more positive interactions between puppies, including play, were evident in dogs in the DAP groups. Data from follow-up telephone surveys indicated that puppies in the DAP groups were better socialized and adapted faster in new situations and environments, compared with puppies in the placebo groups. When compared with a placebo treatment, DAP was useful in reducing anxiety and fear in puppies during puppy classes and resulted in improved socialization.

MeSH Terms

  • Aging
  • Animal Husbandry
  • Animals
  • Animals, Newborn
  • Anxiety
  • Behavior, Animal
  • Dogs
  • Double-Blind Method
  • Fear
  • Female
  • Human-Animal Bond
  • Humans
  • Male
  • Pheromones
  • Placebos
  • Social Behavior
  • Social Isolation
  • Time Factors


Effects of sleeping position on development of infant cardiovascular control.

Sudden Infant Death Syndrome (SIDS) is associated with prone sleeping, and circulatory failure has been hypothesised to be a factor in the fatal event. We aimed to determine the effect of prone sleeping on heart rate (HR) and blood pressure (BP) control over the first 6 months of life. Term infants (n = 20) were studied longitudinally at 2-4 weeks, 2-3 months and 5-6 months with daytime polysomnography. A photoplethysmographic cuff (Finometer, FMS, Finapres Medical Systems, Amsterdam, The Netherlands) on the infant's wrist measured mean, systolic, and diastolic arterial pressure (MAP, SAP, DAP) and HR during quiet sleep (QS) and active sleep (AS) in both the supine and prone positions. BP in QS was lower compared to AS (by 3-9 mmHg) in both positions and at all three ages (p<0.05). At 2-3 months, a change from supine to prone in QS induced a fall in SAP (6 mmHg, p<0.05) and a rise in HR (4 bpm, p<0.05). An overall effect of postnatal age (PNA) on BP was identified (ANOVA) with MAP and DAP consistently averaging less (by 1-9 mmHg) at 2-3 months in both sleep states and sleeping positions compared with both other ages. Infant BP is modified by sleep state and sleeping position. A tendency for BP to fall in the prone position appears to be prevented by elevated HR at 2-4 weeks and 5-6 months, but not at 2-3 months, coincident with the age of greatest risk for SIDS. An uncompensated fall in BP in the prone position at this age could increase the possibility of circulatory failure and SIDS in vulnerable infants.

MeSH Terms

  • Aging
  • Blood Pressure
  • Electrocardiography
  • Female
  • Heart Rate
  • Humans
  • Infant Care
  • Infant, Newborn
  • Longitudinal Studies
  • Male
  • Oxygen
  • Partial Pressure
  • Polysomnography
  • Prone Position
  • Respiratory Physiological Phenomena
  • Skin Temperature
  • Sleep


[Analysis of arterial hypertension and work in the epidemiologic study "Aging, Health and Work"].

We evaluated if work conditions or job strain related to professional activity or to life styles represent a risk factor for arterial hypertension and whether this effect of hypertension is independent of age. through data collection of epidemiological inquiries ESTEV and VISAT, applied in Italy on a cohort of workers, 32-52 year-old, employed in different productive sectors, we analyzed the relationships on working conditions (exposure to certain risks or job strain), life styles and self evaluation of health and arterial hypertension. Hypertension was considered as SAP > or =160 mm/Hg and/or DAP > or =90 mm/Hg, or current antihypertensive treatment. the results refer to 1104 workers, 76% men and 24% women. Prevalence of hypertension was found to be higher among the men than women (33% vs. 22%). Risk estimation in multivariate analysis, by logistic regression model, showed a statistically significant association with certain work-related factors such as: shift work, awkward posture, standing work, doing several tasks contemporarily, being interrupted at work, not being able to take eyes off work. The variables referred to cognitive aspects and work organization tended to be associated to arterial hypertension even when exposure ceased. both physical and cognitive organisational aspects of work are strongly associated with arterial hypertension. The subjective assessment that workers give to their work is a relevant element. This aspects should be considered as a possible reducible risk factor.

MeSH Terms

  • Adult
  • Age Distribution
  • Age Factors
  • Aging
  • Cohort Studies
  • Female
  • Health Status
  • Humans
  • Hypertension
  • Italy
  • Life Style
  • Male
  • Middle Aged
  • Occupational Diseases
  • Prevalence
  • Risk Factors
  • Sex Distribution
  • Stress, Psychological
  • Surveys and Questionnaires
  • Work
  • Work Schedule Tolerance
  • Workload


Aging of phrenic nerve conduction in the elderly.

We elucidated the possible relationship between age and conduction parameters of phrenic nerve in subjects above the sixth decade, comparing with the data from middle-age controls. Diaphragmatic action potentials (DAPs) were recorded on bilateral hemithoraces of 41 volunteers aged 60-101 years (old group) and 25 volunteers aged 35-55 years (middle-age group). Statistical analyses were performed to assess the effects of aging on latency, latency corrected by size (Lat/Dist), amplitude, and the right-left difference of these DAP parameters. In all 61 subjects, age showed a significant quadratic correlation with latency and with Lat/Dist, and a linear correlation with amplitude. The right-left differences ranged from 0.0 to 14.5% for latency and from 6.5 to 112.4% for amplitude in the elderly. The normal ranges of DAP parameters should be determined according to age. The left-right difference may be a useful reference in diagnosing unilateral phrenic nerve lesion. The precise normal ranges of phrenic nerve conduction parameters presented will encourage investigations of neuropathies in subjects aged above 60.

MeSH Terms

  • Action Potentials
  • Adult
  • Aged, 80 and over
  • Aging
  • Diaphragm
  • Female
  • Functional Laterality
  • Humans
  • Male
  • Middle Aged
  • Neural Conduction
  • Phrenic Nerve
  • Reaction Time
  • Reference Values
  • Sex Characteristics


Cognitive deficits in aged rats correlate with levels of L-arginine, not with nNOS expression or 3,4-DAP-evoked transmitter release in the frontoparietal cortex.

Aging is associated with altered neurotransmitter function in the brain. In this study, we measured release parameters for acetylcholine (ACh), norepinephrine and serotonin in the frontoparietal cortex of young and aged rats. We also determined cortical amino acid concentrations and nitric oxide (NO) synthase function. Prior to sacrifice, the rats had been tested for Morris water-maze performance. In aged, compared with young rats, we observed a reduction in both uptake of choline and acetylcholine release. Serotonin release and L-arginine concentrations (a precursor of NO) showed an aging-related increase; however, L-citrulline/L-arginine ratios were decreased in aged rats. Moreover, while most age-related changes in transmitter release or neurochemical markers were not related to the learning performance, L-arginine concentrations were positively correlated to cognitive deficits. NO synthase concentrations were not affected by aging. It is suggested that events related to L-arginine-to-L-citrulline/NO metabolism in the frontoparietal cortex may take part in age-related cognitive deficits.

MeSH Terms

  • 4-Aminopyridine
  • Acetylcholine
  • Aging
  • Amifampridine
  • Animals
  • Arginine
  • Cerebral Cortex
  • Cognition Disorders
  • Female
  • Frontal Lobe
  • Gene Expression Regulation
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Norepinephrine
  • Parietal Lobe
  • Rats
  • Rats, Long-Evans
  • Serotonin


Survival of egg-laying controlling neuroendocrine cells during reproductive senescence of a mollusc.

During brain aging neuronal degradation occurs. In some neurons this may result in degeneration and cell death, still other neurons may survive and maintain their basic properties. The present study deals with survival of the egg-laying controlling neuroendocrine caudodorsal cells (CDCs) during reproductive senescence of the pond snail Lymnaea stagnalis. In senescent animals CDCs exhibited reduced branching patterns but still maintained their electrophysiological characteristics. In the isolated CNS the cells could still respond with an afterdischarge upon electrical stimulation. After an extended period of no egg laying of Lymnaea CDCs failed to exhibit an afterdischarge. In senescent CDCs that failed an afterdischarge, discharge activity could be restored by exposure to peptides released by CDCs from reproductive animals. Moreover, raising the intracellular cAMP level could induce discharge activity in CDCs with afterdischarge failure. Discharge activity also occurred during depolarization of senescent CDCs by exposure of the cells to saline with a high potassium concentration. These results indicate that in senescent CDCs the pacemaking mechanism of the afterdischarge is still intact but that the initial activation fails. Chemical (auto)transmission of CDCs in such animals was indeed reduced as indicated by the small amplitude of the depolarizing afterpotential (DAP) induced by electrical stimulation. Interestingly, CDCs of senescent animals contained a relative large amount of a particular small peptide. The artificially synthesized peptide appeared to suppress DAP induction in CDCs. Possibly, release of the peptide contributes to the prevention of afterdischarge induction in senescent CDCs. The results so far indicate that in senescent Lymnaea neurons electrophysiological functions persist even after long periods of inactivity and severe morphological reduction.

MeSH Terms

  • Aging
  • Animals
  • Central Nervous System
  • Cyclic AMP
  • Electrophysiology
  • Female
  • Mollusca
  • Neurons
  • Neurosecretory Systems
  • Oviposition
  • Peptides
  • Potassium
  • Reproduction
  • Time Factors


Promoter methylation status of tumor suppressor and tumor-related genes in neoplastic and non-neoplastic gastric epithelia.

A number of tumor suppressor and tumor-related genes exhibit promoter hypermethylation with resulting gene silencing in human cancers. In addition, several gene promoters have also been shown to become hypermethylated in non-neoplastic cells during aging. To assess the physiological consequence and clinical significance of gene promoter methylation in gastric epithelia, our laboratory has studied the methylation status of tumor suppressor and tumor-related genes, including APC, DAP-kinase, DCC, E-cadherin, GSTP1, hMLH1, p16, PTEN, RASSF1A, RUNX3 and TSLC1, in neoplastic and non-neoplastic gastric epithelia. The tumor suppressor and tumor-related genes, except APC, were generally unmethylated in non-neoplastic gastric epithelia obtained from younger individuals. The frequencies of methylation increased with age to varying degrees in various genes, although GSTP1 and PTEN methylation was completely absent in both neoplastic and non-neoplastic gastric epithelia. The methylation frequencies in each gene were found to be comparable in neoplastic and non-neoplastic gastric epithelia, except the methylation of RUNX3 and TSLC1, which was mostly cancer-specific (P<0.01). When methylation frequencies were compared between non-neoplastic gastric epithelia from cancer-bearing and non-cancer-bearing stomachs, hMLH1 and p16 methylation was more frequent in those from cancer-bearing stomachs (P<0.01). Promoter methylation in tumor suppressor and tumor-related genes initially occurs in non-neoplastic gastric epithelia, increases with age, and ultimately silences gene function to constitute a field-defect that may predispose tissues to gastric cancer evolution. In clinical applications RUNX3 and TSLC1 methylation may be utilized as molecular diagnostic markers, and hMLH1 and p16 methylation as predictors of malignancy in the stomach.

MeSH Terms

  • Adult
  • Aging
  • Animals
  • DNA Methylation
  • DNA, Neoplasm
  • Epithelial Cells
  • Gastric Mucosa
  • Genes, Tumor Suppressor
  • Humans
  • Incidence
  • Promoter Regions, Genetic
  • Stomach Neoplasms


3,4-DAP-evoked transmitter release in hippocampal slices of aged rats with impaired memory.

Based on a slice superfusion technique, this study investigated the release of acetylcholine, noradrenaline and serotonin in the hippocampus of aged rats (25-27 months) showing no or severe deficits in a spatial reference-memory task (water maze). Young adults (3-5 months) were used as controls. 3,4-diaminopyridine (3,4-DAP), a potassium channel antagonist which increases neuronal excitability, was used to evoke the overflow of the three neurotransmitters. The release of [3H]noradrenaline induced by stimulation of presynaptic nicotinic receptors was also assessed. The experiment compared the accumulation and 3,4-DAP-evoked (or nicotine-evoked) overflow of [3H] in hippocampal slices preincubated with [3H]choline, [3H]noradrenaline, or [3H]serotonin. In aged rats, only the accumulation of [3H]serotonin was reduced significantly (-17%). In percent of tissue-[3H], the 3,4-DAP-evoked overflow of [3H]serotonin was increased ( 28%), and that of [3H]acetylcholine was reduced (-23%) in the aged rats. The nicotine-evoked overflow of [3H]noradrenaline was not altered in aged rats. There was a significant correlation of water-maze performance (distance to platform) and evoked overflow of [3H]serotonin. It is concluded that hippocampal cholinergic functions are more altered by aging than noradrenergic or serotonergic ones. Excessive excitability of serotonergic terminals, perhaps in addition to cholinergic dysfunction, might be a crucial factor accounting for age-related cognitive deficits in the present population of rats.

MeSH Terms

  • 4-Aminopyridine
  • Acetylcholine
  • Aging
  • Amifampridine
  • Animals
  • Female
  • Hippocampus
  • Maze Learning
  • Memory Disorders
  • Neurotransmitter Agents
  • Norepinephrine
  • Organ Culture Techniques
  • Potassium Channel Blockers
  • Rats
  • Serotonin


Aberrant CpG island hypermethylation of chronic gastritis, in relation to aging, gender, intestinal metaplasia, and chronic inflammation.

Aberrant hypermethylation of promoter CpG islands is an important mechanism for the inactivation of tumor suppressor genes. CpG island hypermethylation occurs in relation to tumorigenesis or aging. Gastric cancer is one of the tumors with a high level of aberrant CpG island methylation. However, the data on the methylation status of normal gastric mucosa has been very limited. The present study attempted to compare the methylation status of nonneoplastic gastric mucosa, using clinicopathological parameters, including age, gender, Helicobacter pylori (H. pylori), acute and chronic inflammation, and intestinal metaplasia. Two hundred sixty-eight nonneoplastic gastric mucosa samples were studied for the methylation status of 11 genes (COX-2, DAP-kinase, E-cadherin, GSTP1, MGMT, hMLH1, p14, p16, THBS1, TIMP3, and RASSF1A), using methylation-specific PCR. CpG island hypermethylation was found in 53.7, 41, 37.7, 23.1, 18.7, 10.9, 10, 4.1, 3.4, 1.7, 0.4% for DAP-kinase, E-cadherin, THBS1, TIMP3, p14, MGMT, p16, COX-2, GSTP1, hMLH1 and RASSF1A, respectively. Five genes (DAP-kinase, E-cadherin, p14, THBS1, and TIMP-3) showed a general progressive increase in the methylation frequency as a function of aging, whereas the other genes (COX-2, GSTP1, MGMT, hMLH1, p16, and RASSF1A) were rarely methylated. Male patients showed higher numbers of methylated genes than females (3.2 vs. 2.1, respectively, P = 0.002). Gastritis samples with marked intestinal metaplasia, showed higher numbers of genes methylated than those without (3.7 vs. 2.6, respectively, P = 0.021). Gastritis samples with marked infiltration of mononuclear cells displayed higher numbers of genes methylated than those with mild or moderate infiltration of mononuclear cells (3.4 vs. 2.5 or 2.5, respectively, P < 0.05). Our results demonstrated that many genes are methylated in the stomach as a function of age, and suggested that male gender, intestinal metaplasia, and chronic inflammation are closely associated with increased methylation in nonneoplastic gastric mucosa samples.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aging
  • Child
  • Child, Preschool
  • Chronic Disease
  • CpG Islands
  • DNA Methylation
  • Female
  • Gastritis
  • Humans
  • Intestines
  • Male
  • Metaplasia
  • Middle Aged
  • Sex Characteristics


A decision between life and death during TNF-alpha-induced signaling.

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, exerts its biological activity by signaling via its two receptors, TNF-RI and TNF-RII, and by activating NF-kappaB. NF-kappaB is essential for survival of many cell types; however, TNF-alpha also induces cell death. In this article, both the survival and cell death signaling by TNF-alpha and the role of caspases in turning off NF-kappaB survival signal are reviewed. Furthermore, a role of DAP kinase in TNF-induced apoptosis is discussed. Finally, the molecular basis of the effect of age on TNF-alpha-induced apoptosis in human T cells is reviewed.

MeSH Terms

  • Aging
  • Antigens, CD
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Caspases
  • Cell Survival
  • Death-Associated Protein Kinases
  • Humans
  • Mitochondria
  • Models, Immunological
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Signal Transduction
  • Tumor Necrosis Factor-alpha


Empirical estimates of mean aortic pressure: advantages, drawbacks and implications for pressure redundancy.

Mean arterial pressure (MAP) is estimated at the brachial artery level by adding a fraction of pulse pressure (form factor; =0.33) to diastolic pressure. We tested the hypothesis that a fixed form factor can also be used at the aortic root level. We recorded systolic aortic pressure (SAP) and diastolic aortic pressure (DAP), and we calculated aortic pulse pressure (PP) and the time-averaged MAP in the aorta of resting adults (n=73; age 43 /-14 years). Wave reflection was quantified using the augmentation index. The aortic form factor (range 0.35-0.53) decreased with age, MAP, PP and augmentation index (each P<0.001). The mean form factor value (0.45) gave a reasonable estimation of MAP (MAP=DAP 0.45PP; bias=0 /-2 mmHg), and the bias increased with MAP (P<0.001). An alternative formula (MAP=DAP PP/3 5 mmHg) gave a more precise estimation (bias=0 /-1 mmHg), and the bias was not related to MAP. This latter formula was consistent with the previously reported mean pulse wave amplification of 15 mmHg, and with unchanged MAP and diastolic pressure from aorta to periphery. Multiple linear regression showed that 99% of the variability of MAP was explained by the combined influence of DAP and SAP, thus confirming major pressure redundancy. Results were obtained irrespective of whether the marked differences in heart period and extent of wave reflection between subjects were taken into account. In conclusion, the aortic form factor was strongly influenced by age, aortic pressure and wave reflection. An empirical formula (MAP=DAP PP/3 5 mmHg) that is consistent with mechanical principles in the arterial system gave a more precise estimate of MAP in the aorta of resting humans. Only two distinct pressure-powered functions were carried out in the (SAP, DAP, MAP, PP) four-pressure set.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Aorta
  • Blood Pressure
  • Female
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Models, Cardiovascular
  • Prospective Studies
  • Pulsatile Flow
  • Reference Values


Electrophysiologic and inotropic effects of K -channel blockade in aged diaphragm.

The aminopyridines block several types of potassium (K ) channels and exert a direct inotropic effect on skeletal muscle by prolonging the duration of the action potential. Aging influences skeletal muscle Cl- channels and their regulation, and affects both resting whole-cell K conductance and adenosine triphosphate (ATP)-sensitive K channels, although in opposite directions. The present study tested the hypothesis that aging affects diaphragm-muscle K channels responsible for repolarization of the action potential and force production. Diaphragms of young adult (age 3 to 4 mo) and old (age 20 to 21 mo) male Fischer 344 rats was studied in vitro at 37 degrees C. The K -channel blocker 3,4-diaminopyridine (DAP, 0.3 mM) did not alter resting membrane potential or action-potential height, overshoot, or rate of depolarization of either young-adult or old muscle. However, DAP slowed the rate of repolarization of the action potential and increased the action-potential area in young-adult and old muscle; the time for the action potential to repolarize by 80% increased from 0.59 /- 0.02 ms (mean /- SE) to 3.37 /- 0.68 ms (p < 0.05) in young-adult muscle and from 0.87 /- 0.06 ms to 2.52 /- 0.54 ms (p < 0.05) in old muscle, whereas the action-potential area increased from 56 /- 3 mVms to 193 /- 34 mVms (p < 0.05) in young-adult muscle and from 72 /- 5 mVms to 134 /- 20 mVms (p < 0. 05) in old muscle. The action-potential area was not different in young-adult and old diaphragm without DAP, but was significantly larger in young-adult than in old diaphragm with DAP (p < 0.05). The functional consequence was that DAP increased diaphragm isometric twitch force by 181 /- 12% (p < 0.05) in young-adult muscle and by 144 /- 24% (p < 0.05) in old muscle; the increase was significantly greater in young-adult than in old muscle (p < 0.05). These data suggest an aging-associated reduction in, or reduced DAP sensitivity of, diaphragm K conductance during action potentials, which most likely reflects aging-associated alterations in delayed-rectifier K conductance. Although the inotropic effect of DAP was greater for young-adult than for old diaphragm muscle, the difference was sufficiently modest to show that DAP has substantial inotropic effects in old muscle.

MeSH Terms

  • 4-Aminopyridine
  • Action Potentials
  • Adenosine Triphosphate
  • Aging
  • Amifampridine
  • Analysis of Variance
  • Animals
  • Chloride Channels
  • Diaphragm
  • Isometric Contraction
  • Male
  • Membrane Potentials
  • Muscle Contraction
  • Muscle, Skeletal
  • Potassium Channel Blockers
  • Rats
  • Rats, Inbred F344
  • Reaction Time


Behaviors and nutritional importance of coprophagy in captive adult and young nutrias (Myocastor coypus).

To estimate the contribution of coprophagy to protein intake, we observed the behavior, particularly that associated with coprophagy, in adult and young captive nutrias (experiment 1), and analyzed chemical composition and amino acid composition, including diaminopimeric acid (DAP), an indication of bacterial-deprived protein, of soft feces, entire hard feces, and the black part and green part of hard feces (experiment 2). Nutrias practiced coprophagy 48 times per 24 h in adults, and 28 times in young animals, which not only had a 24-h rhythm but also had 1-h or 2-h short-term rhythms. Nutrias ingested food and drank water vigorously after sunset, following which they practiced coprophagy from midnight to morning, before lying down for much of the day. When coprophagy was prevented we sampled soft feces, produced from midnight to noon, which had high (P < 0.05) concentration of crude protein (CP), DAP on a dry matter (DM) basis and 13 amino acids on a 16 g N basis than hard feces, and had a low (P < 0.05) content of acid detergent fiber (ADF). CP was greater in the black part than the green part of hard feces (P < 0.05) although ADF was less (P < 0.05). The chemical composition of the black part of hard feces was not significantly different from that of soft feces. The dry weight of soft feces excreted in experiment 1 was 34.5 g and 9.7 g DM per 24 h in adult and young animals, respectively. Using this value, the contribution of soft feces to CP intake in adult nutrias was estimated as 16%, superior to that obtained in rabbits for a diet with similar ADF concentration. To Met and Lys intake the contribution of soft feces was 26% and 19%, respectively in adult animals. These results suggest that coprophagy is quite an effective manner for nutrias to ingest extra protein.

MeSH Terms

  • Aging
  • Amino Acids
  • Animals
  • Circadian Rhythm
  • Coprophagia
  • Dietary Proteins
  • Feces
  • Nutritional Status
  • Rodentia
  • Video Recording


Molecular cloning and developmental expression of a rat homologue of death-associated protein kinase in the nervous system.

Death-associated protein kinase (DAP kinase) has been recently identified as a novel Ca2 /calmodulin-dependent protein kinase and as a potential mediator of gamma interferon-induced cell death of Hela cells, which has cytological characteristics of the programmed cell death. In order to elucidate its functional roles in the rat brain where the programmed cell death is an essential mechanism in the organization of postmitotic neurons during development, we cloned a rat homologue of the human DAP kinase from the rat embryonic brain cDNA library. The deduced amino acid sequence was highly conserved between the two species (93.6%). By in situ hybridization histochemistry, the expression of DAP kinase mRNA was observed in the mantle and ventricular zones of the entire neuraxis on embryonic day 15. However, the overall expression in the brain decreased markedly after birth and the expression was maintained at substantial levels in several restricted mature neuronal populations, such as olfactory bulb, hippocampal formation and cerebellar Purkinje and granule cells. Its wide expression during development and its maintained expression in the restricted mature neuronal population suggest that DAP kinase might be involved in some neuronal functions beyond simply executing the developmental neuronal cell death.

MeSH Terms

  • Aging
  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Brain
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cloning, Molecular
  • Death-Associated Protein Kinases
  • Embryonic and Fetal Development
  • Gene Expression Regulation, Developmental
  • Gene Library
  • Gestational Age
  • HeLa Cells
  • Humans
  • Male
  • Molecular Sequence Data
  • Organ Specificity
  • RNA, Messenger
  • Rats
  • Spinal Cord
  • Transcription, Genetic


Body image in adulthood: a projective approach.

A sample of 210 persons varying by age (young adults, middle-aged, older adults), gender, and relationship status (single or involved) were administered the Holtzman Inkblot Technique (HIT) and Geriatric Draw-A-Person (G-DAP) to ascertain projectively assessed aspects of body image in adulthood. Results suggested that both the HIT and G-DAP were sensitive to the effects of age and gender, wherein young adults scored higher on both HIT Barrier and Penetration than both middle-aged or older adults. In addition, G-DAP scores favored young adults. HIT Penetration scores varied by both age and relationship status.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Body Image
  • Defense Mechanisms
  • Female
  • Geriatric Assessment
  • Holtzman Inkblot Test
  • Humans
  • Male
  • Middle Aged
  • Projective Techniques
  • Psychometrics
  • Reference Values
  • Social Conformity
  • Social Values


Camerano study on hypertension: the problem of blood pressure variability during medical visit.

The Camerano Study on Arterial Hypertension (AH) is a cross-sectional study, carried out on a wide population sample in a small town in Central Italy, and aimed at revealing the prevalence of certain characteristics of AH in the population examined. In particular, we studied some aspects of blood pressure (BP) levels during the medical visits. To evaluate the effects of the medical visit on BP levels, we divided the subjects into 3 groups: I) Hypertensive subjects, II) Treated hypertensive subjects, III) Normotensive subjects (control group). The Systolic Arterial Pressure (SAP) in normotensive subjects reached maximum levels during the first medical visit and then decreased in the following two controls (p < 0.001). The Diastolic Arterial Pressure (DAP) did not show any significant changes during the three measurements (p = n.s.). Instead the maximum level of SAP in the hypertensive group did not appear at the first measurement but only after 5 minutes and was seen to decrease towards the end of the visit (p < 0.001). Even DAP showed different levels compared to the normotensives: a decrease in BP levels was registered after 15 minutes respect to earlier measurements (p < 0.01). The levels of group II were similar to those of normotensive subjects.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Blood Pressure
  • Cross-Sectional Studies
  • Diastole
  • Female
  • Humans
  • Hypertension
  • Male
  • Middle Aged
  • Office Visits
  • Sex Characteristics
  • Systole


Contribution of the low-threshold T-type calcium current in generating the post-spike depolarizing afterpotential in dentate granule neurons of immature rats.

1. The underlying ionic mechanisms of the postspike depolarizing afterpotential (DAP) in hippocampal dentate granule (DG) neurons of immature rats (postnatal 7- to 17-day-old) were examined using whole cell patch recordings in brain slices. 2. In current-clamp mode, the DAP followed each single action potential. Graded DAP-like responses were also evoked by depolarizing current pulses when the action potential was blocked by tetrodotoxin (TTX), demonstrating that the TTX-sensitive Na conductance is not necessary for DAP generation. The membrane resistance near the DAP peak was lower than at rest, suggesting activation of inward currents rather than blockade of outward currents during the DAP. The DAP peak amplitude showed a strong dependence on voltage, increasing with membrane hyperpolarization and decreasing with depolarization in the range of -90 to -50 mV. Repetitive stimulation at 1-2 Hz did not change the amplitude or decay of the DAP or DAP-like response. 3. Bath application of 2 mM 4-aminopyridine (4-AP) and 5 mM tetraethylammonium chloride (TEA) prolonged the action potential and enhanced the DAP, suggesting that the DAP waveform is determined by the interaction of voltage-activated outward K currents and inward currents. 4. Bath application of 2 mM Co2 depressed the DAP and the DAP-like potential. Replacement of extracellular Ca2 with Ba2 potentiated the DAP. Intracellular Ca2 chelation with the fast chelator, bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA), only slightly enhanced the DAP, suggesting that the DAP is not generated by inward currents activated secondary to Ca2 influx.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms

  • 4-Aminopyridine
  • Aging
  • Animals
  • Animals, Newborn
  • Calcium Channel Blockers
  • Calcium Channels
  • Culture Techniques
  • Electric Stimulation
  • Hippocampus
  • Limbic System
  • Male
  • Membrane Potentials
  • Neural Pathways
  • Neuronal Plasticity
  • Potassium Channels
  • Rats
  • Rats, Wistar
  • Synaptic Transmission
  • Tetraethylammonium
  • Tetraethylammonium Compounds


Immunohistochemical localization of dipeptidyl aminopeptidase (DAP) IV in the rat submandibular gland during postnatal development.

The localization of dipeptidyl aminopeptidase (DAP) IV in the rat submandibular gland during postnatal development was studied immunohistochemically using the unlabeled antibody enzyme method. Cryostat sections of rat submandibular glands were examined in animals 1 to 50 days old. In the first postnatal week, faint immunoreaction was detected in the apical region of the cytoplasm of terminal tubules. During the second postnatal week the reaction was gradually restricted to the luminal region of terminal tubules or developing acinar cells, and its intensity increased. The most striking change of the enzyme localization was observed in 15-day-old rats. At this time, DAP IV was confined to the luminal and lateral membranes of differentiated acinar cells and to the luminal membranes of intercalated and striated duct cells. This localization pattern was similar to that of the adult animal. DAP IV activity in the gland was also measured biochemically during the postnatal development. The results were in agreement with those of the immunohistochemical study. These results suggest that the localization of DAP IV is closely related to the postnatal differentiation and proliferation of acinar cells.

MeSH Terms

  • Aging
  • Animals
  • Animals, Newborn
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Endopeptidases
  • Female
  • Histocytochemistry
  • Immunoenzyme Techniques
  • Male
  • Rats
  • Rats, Inbred Strains
  • Submandibular Gland


Tetrahydroaminoacridine, 3,4 diaminopyridine and physostigmine: direct comparison of effects on memory in aged primates.

The effects of tetrahydroaminoacridine (THA), 3,4 diaminopyridine (3,4 DAP) and physostigmine were evaluated for their ability to reduce memory impairments in aged, test-sophisticated cebus monkeys (18 to 26 years old). Several doses of each drug were tested (PO) in each of ten different monkeys, allowing for direct and extensive comparison of each drug's efficacy in this model. The results of this comparative test revealed several potentially interesting findings: (1) all drugs produced improvement in a portion of the monkeys tested; (2) as in many past tests with aged monkeys and humans, wide variations in most effective dose, per subject, were observed; (3) different monkeys responded more effectively to one drug than another; and (4) under these tightly controlled conditions, physostigmine produced the most reliable and robust effects (p less than 0.005), in more monkeys, than did either THA (p less than 0.05) or 3,4 DAP (p less than 0.10).

MeSH Terms

  • 4-Aminopyridine
  • Aging
  • Amifampridine
  • Aminopyridines
  • Animals
  • Cebidae
  • Cebus
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Memory Disorders
  • Physostigmine


Afterpotential characteristics and firing patterns in maturing rat hippocampal CA1 neurones in in vitro slices.

The postnatal evolution of depolarizing after-potentials (DAPs) and after-hyperpolarizations (AHPs) was studied in rat CA1 hippocampal neurones (5-68 days of age) using in vitro slices. Results were pooled into 4 age groups: P5-9, P10-16, P17-24 and P26-68. In P5-9 cells, DAPs were seen as passive signals, with a time constant similar to the time constant of the membrane. The evolution of the DAP was characterized by a decrease in amplitude, an increase in duration and a change in contour. In P10-16 and P17-24 cells, the DAPs often had a plateau or a hump-like shape which increased the probability of firing and the occurrence of spike doublets. The firing pattern and bursting behaviour of P10-16 CA1 neurones differed from the pattern typical of the adult. P5-9 and P10-16 cells had post-burst AHPs with a smaller amplitude and a more prolonged early phase than at late stages of development.

MeSH Terms

  • Action Potentials
  • Aging
  • Animals
  • Electrophysiology
  • Female
  • Hippocampus
  • In Vitro Techniques
  • Male
  • Neurons
  • Rats
  • Rats, Inbred Strains
  • Reaction Time