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A Arai

Publications and source records attributed to A Arai.

At least 91 records · Page 5Linked to original sources

A brief period of hypoxia causes proteolysis of cytoskeletal proteins in hippocampal slices.

Breakdown products (BDPs) resulting from the partial proteolysis of spectrin were examined in hippocampal slices after periods of hypoxia lasting for 5 or 10 min. The concentration of a approximately 155 kDa BDP increased nearly twofold after 5 min of hypoxia; further increases were not seen with 10 min episodes or 10 min of hypoxia followed by reoxygenation. The hypoxia-induced proteolysis was blocked by prior infusion of a newly introduced inhibitor of calpain (calpain inhibitor I, 200 microM). Together with previously published data showing improved recovery of hippocampal slices from hypoxia in the presence of calpain inhibitors, these data suggest that activation of calpain may contribute significantly to the pathophysiology of ischemia.

Animals↗

Growth and cell kinetics of human hair papilla cells in vitro. An autoradiographic and flow cytometric study.

Hair papilla, a distinct specialized dermal compartment, plays a fundamental role in the biology of hair growth. Recently some attention has been focused on hair papilla cells (HPC) as possible targets for drugs influencing the hair growth. Isolation and cultivation of the HPC facilitates screening for such drugs. In the present work, growth and cell kinetics of human occipital scalp follicle HPC have been studied in vitro. HPC grow according to a Gompertz function, i.e. with considerable growth delay long before becoming confluent cultures, due probably to elongation of the potential doubling time (Tpot) and to a parallel increasing cell loss rate. The [3H]dT labelling index of the HPC strongly depends on the age of the subculture; the cycle time being about 4 days. A potential doubling time of about 93 h, indicative of growth fraction (GF) = 1, and a duration of S phase and G2 + M phase of about 8 h each were found by the combined application of continuous labelling with [3H]dT and DNA flow cytometry.

Adult↗

Calpain inhibitors improve the recovery of synaptic transmission from hypoxia in hippocampal slices.

Two inhibitors of calcium activated proteases (calpains) were tested for their effects on hypoxia-induced synaptic dysfunction in hippocampal slices. Hypoxic episodes lasting for either one or two minutes beyond the point at which action potentials (fiber volleys) disappeared were used. Leupeptin and calpain inhibitor I had no reliable effects on the rate at which synaptic transmission declined during hypoxia or the time required for loss of action potentials, but both drugs did substantially improve the degree of recovery. Moreover, the percentage of slices meeting an arbitrary criterion for viability after hypoxic treatment was greatly increased by the drug treatment. These results point to the conclusion that proteolysis triggered by calcium influx during hypoxia contributes to pathophysiology.

Animals↗

The effects of adenosine on the development of long-term potentiation.

In previous work we found that a brief period of hypoxia occurring within 1-2 min of high-frequency stimulation disrupts the development of long-term potentiation (LTP) in the CA1 field of rat hippocampal slices. We now report that extracellular application of adenosine if applied within 1 min but not 5 min after high-frequency stimulation similarly prevents LTP. Adenosine was ineffective if DPCPX (1,3-dipropyl-8-cyclopentyl-xanthine), a selective antagonist of adenosine A1 receptors, was present. The post-stimulation application mode excludes the possibility that adenosine interferes with NMDA receptor activation and its role in initiating LTP. It suggests instead that changes in intracellular control systems linked to adenosine receptors can during a brief vulnerable period interrupt the biochemical processes leading to the expression of long-term potentiation.

Adenosine↗

Anoxia reveals a vulnerable period in the development of long-term potentiation.

Transient anoxia occurring 1-2 min after high-frequency stimulation selectively prevented the stable expression of long-term potentiation (LTP). Anoxia occurring after this brief vulnerable period did not reverse LTP. Experiments on the duration of anoxia necessary to block LTP expression indicated that simply reducing synaptic transmission was insufficient but that membrane depolarization was not required. The effects of anoxia on LTP were blocked by antagonists of A1 adenosine receptors. It is concluded that LTP develops in about one minute and that the chemistries operating in this period are easily disrupted by an event triggered by adenosine receptors.

Action Potentials↗

Induction of ornithine decarboxylase by subseizure stimulation in the hippocampus in vivo.

Electrical stimulation of the Schaffer-collateral axonal system under conditions which do not elicit detectable seizure activity causes an increase in the activity of ornithine decarboxylase (ODC), the rate limiting enzyme of polyamine synthesis, in the hippocampus, olfactory cortex, neocortex and olfactory bulb. The degree of ODC activation is dependent upon the stimulus parameters. The results support the hypothesis that neuronal activity regulates hippocampal polyamine concentrations.

Animals↗

The nature and causes of hippocampal long-term potentiation.

One of the most fascinating features of the hippocampus is its capacity for plasticity. Long-term potentiation (LTP), a stable facilitation of synaptic potentials after high-frequency synaptic activity, is very prominent in hippocampus and is a leading candidate memory storage mechanism. Here, we discuss the nature and causes of LTP and relate them to endogenous rhythmic neuronal activity patterns and their potential roles in memory. Anatomical studies indicate that LTP is accompanied by postsynaptic structural modifications while pharmacological studies strongly suggest that LTP is not due to an increase in presynaptic transmitter release. In field CA1, LTP induction appears to be triggered by a postsynaptic influx of calcium through NMDA receptor-linked channels. Possible roles of several calcium-sensitive enzyme systems in LTP are discussed and it is argued that activation of a calcium-dependent protease (calpain) could produce the structural changes linked to LTP. Rhythmic bursting activity is highly effective in inducing LTP and it is argued that the endogenous hippocampal theta rhythm plays a role in LTP induction in vivo. Finally, studies indicate that LTP and certain types of memory share a common pharmacology and the use of electrical brain stimulation as a sensory cue suggests that LTP develops when the significance of that cue is learned.

Action Potentials↗

Segmental cell kinetics of the human anagen hair: a DNA-flow cytometric analysis.

The cell kinetics of anagen scalp hair taken by punch biopsies from 70 healthy male volunteers were determined at nine different defined bulbar and follicular hair segments using microdissection and DNA-flow cytometry. The highest mean proliferative activity (S-phase) was measured within the lowermost bulbar segment (14.0%), but decreased to 7.6% at Auber's segment and to 5.9% at the follicle isthmus. Notably, the S-phase data of the upper follicular segments (subdermal 2.4%, infundibular 2.4%) were found to be similar to those of the epidermis (2.5%). This study supporting and supplementing former autoradiographic investigations on human hair matrix epithelium clearly demonstrates the main proliferative activity of the anagen hair follicle being localized in the bulbar segments below Auber's level. Moreover, the method described is well suited for studying the effects of agents influencing cell growth (e.g., hormones or drugs) on the cell kinetics of different anagen hair compartments.

Adult↗

Regeneration of myocardial phosphocreatine in pigs despite continued moderate ischemia.

The effects of 1 hour of mild and moderate reductions in coronary blood flow on myocardial high-energy phosphate levels were evaluated. Thirty anesthetized pigs were instrumented with left anterior descending arterial and venous catheters, crystals for instantaneous wall thickness, and a fluid-filled occluder. Measurement of myocardial blood flow was performed with microspheres, and a series of myocardial biopsies also was performed. In 10 pigs, overall coronary blood flow was lowered by 22%, with a fall in subendocardial-to-subepicardial flow ratio from 1.11 to 0.54 and in wall thickening from 33% to 15%. Subendocardial flow fell 48%. Coronary blood flow and thickening were constant during 1 hour of ischemia. Phosphocreatine (mumol/g wet wt) in the subendocardial third of the ischemic zone fell from 7.6 to 3.8 at 5 minutes of ischemia (p less than 0.005 versus control) and returned to normal (7.9) at 60 minutes (p = NS), despite ongoing ischemia. Subendocardial ATP (mumol/g wet wt) fell slowly from 4.3 and leveled off at 2.1 at 60 minutes of ischemia (p less than 0.001 versus control). Similar regeneration of phosphocreatine was found in seven additional pigs, with a 43% transmural reduction in coronary blood flow and a 66% reduction in subendocardial flow. No significant changes in ATP and phosphocreatine were noted in two different control groups (n = 13 pigs). The regeneration of phosphocreatine despite ongoing ischemia and low ATP levels was not related to changes in myocardial oxygen demand or consumption, or in regional function during the period of ischemia. This may reflect 1) a successful downregulation of the energy needs of the ischemic myocardium to maintain cell viability, or 2) a metabolic abnormality in the ability of the cells to produce ATP primarily or by use of phosphocreatine.

Adenosine Triphosphate↗

In vitro effects of testosterone, dihydrotestosterone and estradiol on cell growth of human hair bulb papilla cells and hair root sheath fibroblasts.

The influence of testosterone, dihydrotestosterone (each 10 ng/ml up to 300 ng/ml) and estradiol (0.2 ng/ml up to 10 ng/ml) on the growth behaviour (cell count, [3H]thymidine uptake, cell doubling time) of subcultured human hair bulb papilla cells and hair root sheath fibroblasts was studied. Papilla cells and root sheath fibroblasts were isolated by microdissection from the same anagen hair follicles obtained from biopsies of androgen-sensitive scalp regions in 6 healthy male subjects. Dihydrotestosterone and testosterone concentrations above 30 ng/ml significantly reduced the growth of both cell types; lower doses had no effect. Estradiol had no distinct influence on the growth curves of either cell type up to 10 ng/ml, whereas higher concentrations significantly increased the growth of both cell types as shown by [3H]thymidine uptake. Papilla cells reacted more sensitively than root sheath fibroblast to dihydrotestosterone and testosterone, as shown by the growth curves, [3H]thymidine uptake, and cell doubling time.

Adult↗

Current management of the Wolff-Parkinson-White syndrome.

The Wolff-Parkinson-White syndrome is a multifaceted disorder that ranges from asymptomatic to life threatening. Accounting for approximately 20% of cases of paroxysmal supraventricular tachycardia and with a prevalence perhaps as high as 1 per 500, it is far from a rare disorder. Considering the potentially lethal complications following the administration of digoxin or verapamil, all physicians treating arrhythmias should know when to suspect the Wolff-Parkinson-White syndrome. A careful review of electrocardiograms helps identify cases of the disorder despite a wide range of findings that may mimic other conditions. Major advances in the efficacy of surgical procedures to cure this syndrome make this a reasonable alternative to life-long medical therapy for many patients. Unfortunately, available diagnostic tests lack the positive predictive value to reliably distinguish patients at risk of sudden death. This review is an update for general internists of the major developments in the evaluation and treatment of the disorder and provides specific examples helpful in differentiating these patients.

Electrocardiography↗

Role of association on protein adsorption isotherms. Beta-lactoglobulin A adsorbed on a weakly hydrophobic surface.

This paper explores the role of association on the adsorption isotherms of beta-lactoglobulin A on a weakly hydrophobic stationary phase at 4 degrees C and mobile phases of 0.85 M and 1 M ammonium sulfate, pH 4.5. The isotherms, obtained by frontal analysis, show an S-shape and the corresponding Scatchard plots indicate positive cooperativity. The slopes and intercepts of the Scatchard plots at low solute concentration are analyzed in terms of two species--a promoter and a higher order stronger adsorbing species. An explicit equation of the isotherm is developed based on this model, and this expression is shown to reproduce the isotherm shape using the appropriate derived parameters. It is further shown from this equation that a Langmuir-shaped adsorption isotherm can be obtained if the higher order associate or aggregate binds weaker to the support than the promoter. These results indicate that protein-protein interactions and the formation of associates can play a significant role on the shape of the isotherm and ultimately on the behavior of the species in preparative scale chromatography.

Adsorption↗

Influence of topically applied betamethasone-17-valerate on cell cycle kinetics of human anagen hair determined by DNA flow cytometry.

In 47 healthy volunteers betamethasone-17-valerate (0.1% solution and cream) was topically applied twice daily on the scalp skin. After 7 and 14 days treatment, anagen hairs were plucked in each volunteer from both treated and untreated contralateral scalp areas. Cell cycle analysis of plucked anagen hairs was performed by means of DNA flow cytometry. Already after topical betamethasone-17-valerate application for 7 days, cell kinetic changes were found showing a slightly significant decrease of S and G2 + M cell percentages and a significant increase of G0/1 cell percentages. The present study demonstrates the possibilities of DNA flow cytometry to study the pharmacological effects on cell kinetics of plucked human anagen hairs.

Administration, Topical↗

[DNA impulse cytophotometric studies of the modification of the proliferation behavior of the outer hair root sheath by topical glucocorticoid administration].

A corticoid preparation (C) was topically applied on the scalps of 47 healthy test persons for 7 or 14 days, resp. After this treatment, we plucked anagen hairs under standardized conditions both from the area treated with C and the contralateral, untreated area. The proliferative activity of plucked anagen hairs with root sheaths was analyzed by means of DNA flow cytometry. Already a 7 days treatment with topical C resulted in kinetic changes of the outer root sheath: The percentage of the cells in the G1/10-phase of the cell cycle was increased, whereas that of the cells in the S-phase and the G2+M-phase was decreased.

Betamethasone↗