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Biomedical subjects

A Akabayashi

Publications and source records attributed to A Akabayashi.

36 records · Page 2Linked to original sources
PubMed1997

Hypothalamic galanin gene expression and peptide levels in relation to circulating insulin: possible role in energy balance.

The peptide galanin (GAL) exists in dense concentrations within the medial hypothalamus and is synthesized in a population of neurons within the paraventricular nucleus (PVN). This peptide has been linked to energy homeostasis through its behavioral, metabolic and endocrine actions, including pancreatic insulin secretion. This investigation examined whether circulating insulin, in turn, has impact on hypothalamic GAL production, GAL mRNA and peptide concentrations in the hypothalamus. Streptozotocin (STZ)-induced diabetic rats, compared to control subjects, were tested with or without insulin replacement. After STZ treatment, the rats exhibited hyperglycemia, increased food and water intake, and decreased weight gain compared to controls. These changes were reversed by daily, subcutaneous injections of insulin. Measurements of GAL mRNA, via solution hybridization/nuclease protection assay, revealed a 6-fold elevation after STZ treatment compared to controls, accompanied by a similar rise in GAL peptide levels. This increase in GAL message and peptide was reversible by insulin and was detected in a mediodorsal hypothalamic (MDH) dissection which contains the PVN. It was not seen in a dissection of the mediobasal hypothalamus that includes the GAL-synthesizing neurons of the arcuate nucleus. Measurements of GAL in discrete hypothalamic nuclei of STZ diabetic rats showed a 100% increase in peptide concentrations (p < 0.05) in the PVN that was insulin responsive. Other hypothalamic areas examined failed to exhibit any change in peptide. These findings are consistent with other evidence indicating an inverse association, between circulating insulin and GAL message or peptide in the PVN, that may have physiological relevance in the control of energy balance.

Animals↗
PubMed1997

Organization and patients' perception of palliative care: a crosscultural comparison.

The hospice model of care for patients with advanced diseases exists in almost all industrialized countries. To date, there have been no international or crosscultural comparisons of the organization and patient outcomes associated with hospice services in different parts of the world. This survey evaluated 159 patients in the USA, Germany and Japan. There were differences between countries in the time of first contact, who recommended palliative care first, the underlying diagnoses, the location of patients, and how consent for hospice care was obtained. Across all countries, there were similar levels of comfort and satisfaction with care. We conclude that the hospice philosophy addresses the basic needs of dying patients which are independent of cultural background, but may be adapted to very different cultures.

Aged↗
PubMed1995

Adrenal steroid regulation of neuropeptide Y (NPY) mRNA: differences between dentate hilus and locus coeruleus and arcuate nucleus.

Regulation by adrenal steroids of neuropeptide Y (NPY) mRNA was investigated in hilus of the dentate gyrus, arcuate nucleus of hypothalamus and locus coeruleus (LC) of the adult rat brain. Adrenalectomy (ADX) increased NPY mRNA in hilus but decreased NPY mRNA levels in arcuate nucleus and LC. Using a steroid replacement paradigm previously shown to discriminate between Type I and Type II adrenal steroid receptor mediated effects, it was shown that Type I receptor stimulation by aldosterone prevented the ADX-induced increase of NPY mRNA in hilus, whereas Type II receptor stimulation by Ru28362 prevented the ADX-induced decrease in NPY mRNA in arcuate nucleus and LC. The results for hilus are consistent with evidence for a role of Type I receptors in maintaining levels of a number of gene products associated with neurotransmission. The different regulation in hilus from that in arcuate and LC indicate, along with evidence for regulation of NYP expression by insulin, NGF and cyclic AMP and phorbol esters, that the adrenal steroid regulation of NPY gene expression is part of a complex set of regulatory mechanisms that depend on the brain region and cell type.

Aldosterone↗
PubMed1994

Hypothalamic neuropeptide Y, its gene expression and receptor activity: relation to circulating corticosterone in adrenalectomized rats.

Previous evidence has suggested a possible relationship between the adrenal steroid, corticosterone (CORT) and neuropeptide Y (NPY) in the brain. To provide a more systematic analysis of this interaction, the present study employed a variety of techniques, including in situ hybridization to measure NPY gene expression, radioimmunoassay to examine peptide levels and radioligand [125I]peptide YY (PYY) binding for analysis of peptide receptors. The results show that adrenalectomy (ADX), which caused a decline in CORT to levels < 0.3 micrograms %, has generally little impact on the hypothalamic NPY projection system under normal, basal conditions. This includes peptide gene expression or content in the area of its cell bodies (arcuate nucleus, ARC), in addition to peptide binding at its receptor sites. While it also includes peptide content at most hypothalamic terminal sites, there are three notable exceptions, namely, the medial paraventricular (PVN) and dorsomedial nuclei and medial preoptic area, where NPY nerve terminals and glucocorticoid receptors are particularly dense and the decline in CORT through ADX markedly reduces NPY content. In contrast, evidence obtained from CORT replacement in ADX rats shows that this steroid has profound impact on all components of the hypothalamic NPY system. This peptide-steroid interaction is apparent at the level of the cell body (ARC), as well as at the nerve terminal or receptor site (PVN and ARC), where CORT levels > 10 micrograms % strongly potentiate NPY gene expression, peptide content and radioligand binding. These and other findings suggest that this CORT-NPY interaction in the hypothalamus occurs physiologically under conditions, e.g., at the onset of the active feeding cycle, when circulating CORT normally rises.

Adrenalectomy↗
PubMed1994

Galanin-containing neurons in the paraventricular nucleus: a neurochemical marker for fat ingestion and body weight gain.

The physiological function of the peptide galanin (Gal) remains to be established. It is known to exist in high concentrations within the hypothalamus and to modulate the secretion of specific hormones, as well as to potentiate food consumption. Our study provides evidence for an essential function of neuronal Gal, within a specific hypothalamic area, in stimulating the behavioral process of fat ingestion and body weight gain. Through analyses of peptide levels via RIA and of gene expression via in situ hybridization, a close positive association is established between Gal in the paraventricular nucleus (PVN), particularly its midlateral region, and fat ingestion. No such relationship is detected for Gal in other brain areas or between PVN Gal and ingestion of carbohydrate or protein, supporting the behavioral and anatomical specificity of this relationship. Through PVN injection studies with antisense oligonucleotides to Gal mRNA, a dramatic decline in fat ingestion and body weight suggests that endogenous Gal contributes to the natural appetite for fat. Thus, Gal in the PVN is identified as a neurochemical marker for fat ingestion and, consequently, body weight gain.

Analysis of Variance↗
PubMed1994

Intracerebroventricular injection of dibutyryl cyclic adenosine 3',5'-monophosphate increases hypothalamic levels of neuropeptide Y.

This investigation examined in vivo the relationship between the nucleotide cAMP and hypothalamic levels of two peptides, neuropeptide Y (NPY) and galanin (GAL), which are known to potentiate feeding behavior. In brain-cannulated rats, third ventricular injections of N6,2'-O-dibutyryl cyclic adenosine 3',5'-monophosphate ((Bu)2cAMP, 25 micrograms), compared to saline, caused a significant increase in NPY levels in the arcuate nucleus (ARC) and medial parvocellular portion of the paraventricular nucleus (mPVN), while having no impact in other hypothalamic areas. These site-specific changes in NPY occurred in the absence of any alteration in circulating levels of insulin, corticosterone, aldosterone or glucose, or of changes in hypothalamic levels of GAL. These findings implicate cAMP as having regulatory functions within specific hypothalamic NPY-synthesizing neurons, projecting from the ARC to the mPVN, that are believed to be involved in energy homeostasis.

Aldosterone↗
PubMed1994

Hypothalamic neuropeptide Y and its gene expression: relation to light/dark cycle and circulating corticosterone.

The hypothalamic neuropeptide Y (NPY) system, along with levels of circulating corticosterone (CORT), were examined in rats at different times across the light/dark cycle. Tissue samples were taken from the mediobasal hypothalamus (MBH), which contains the primary hypothalamic NPY cell group of the arcuate nucleus (ARC), and the mediodorsal (MDH) hypothalamus, which contains the paraventricular and dorsomedial nuclei that receive a dense NPY innervation from the ARC. In these dissections, measurements of NPY mRNA and peptide levels were taken using a solution hybridization/nuclease protection assay procedure and radioimmunoassay. The results demonstrate that (i) NPY mRNA levels in the MBH, but not MDH, vary significantly in relation to the light/dark cycle, showing a sharp rise 4-6 h before dark onset, sustained high levels over the next 3-4 h and then, a sharp decline 1 h before dark onset; (ii) this rise in NPY mRNA in the MBH before dark onset, while associated with stable levels of MBH NPY during this time, is followed 2-4 h later, around dark onset, by a rise in NPY peptide levels of the MDH simultaneous to a decrease in NPY levels of the MBH; (iii) levels of circulating CORT shift dramatically across the light-dark cycle, exhibiting an increase from basal levels (< 0.3 microgram/dl) to 5 micrograms/dl approximately 4 h before dark onset, a further rise that peaks at 26 micrograms/dl around dark onset, and then a significant decline to 16 micrograms/dl at 2 h after dark onset; and (iv) there exists a positive relationship between CORT and NPY mRNA or peptide levels in the MBH during the 4-6 h before dark onset, while in the MDH, a positive relationship between this steroid and NPY peptide levels is obtained at dark onset. It is proposed that these rhythms, involving a predark rise in CORT and NPY gene expression leading to a peak in CORT and peptide levels at dark onset, are active in stimulating feeding behavior, particularly carbohydrate ingestion, which predominates at that time.

Adrenocorticotropic Hormone↗
PubMed1994

Hypothalamic galanin-like immunoreactivity and its gene expression in relation to circulating corticosterone.

The neuropeptide galanin (GAL), which exists in dense concentrations within the hypothalamus, has physiological actions which are neuroendocrine in nature. In light of evidence showing GAL to alter the release of the adrenal steroid, corticosterone (CORT), a possible effect of this steroid on GAL gene expression and peptide production in discrete hypothalamic and brainstem sites was investigated. Using radioimmunoassay and in situ hybridization techniques, this peptide was examined in rats that had received SHAM surgery, adrenalectomy (ADX) and ADX+CORT replacement. The results showed a clear, site-specific change in GAL in relation to circulating CORT. A loss of CORT after ADX caused a dramatic decline in GAL peptide and mRNA levels in the arcuate nucleus and peptide levels in the median eminence, with no change occurring in other hypothalamic areas. In the brainstem, a similar change was detected in the dorsal raphe nucleus but not the locus coeruleus. The GAL peptide and mRNA levels in these specific brain areas of ADX rats was restored by CORT replacement, which had no impact on GAL in other brain sites. These findings demonstrate that CORT's impact on brain GAL is highly site specific, possibly determined by local concentrations of steroid receptors.

Adrenal Glands↗
PubMed1994

Specific inhibition of endogenous neuropeptide Y synthesis in arcuate nucleus by antisense oligonucleotides suppresses feeding behavior and insulin secretion.

Neuropeptide Y (NPY), which is synthesized in neurons of the arcuate nucleus (ARC) that project to different hypothalamic nuclei, is known to have potent effects on eating behavior and hormone secretion after hypothalamic administration. To test the hypothesis that endogenous NPY is essential for the normal expression of these responses, the present study used to unmodified antisense oligodeoxynucleotides (ODNs) to disrupt the synthesis of NPY in the ARC and to examine the impact of this disturbance on nutrient intake, as well as on circulating levels of insulin and the adrenal steroids, corticosterone and aldosterone. Brain-cannulated rats maintained on macronutrient diets were given daily, bilateral injections, over a 4-day period, of NPY antisense ODNs, sense ODNs or saline into the ARC. The NPY antisense ODNs produced a significant decline (-33% relative to sense ODNs and -40% relative to saline, P < 0.05) in NPY levels in this nucleus, without causing any direct neural damage. Peptide levels in other hypothalamic areas, namely, the paraventricular nucleus and medial preoptic nucleus, were not significantly affected. In association with this reduction in ARC NPY, the antisense-treated animals exhibited a significant decrease in feeding behavior measured during the first 90 min of the natural feeding cycle, as well as over the 24-h period. In the 90-min interval, both carbohydrate and fat intake were suppressed by 65-70% (P < 0.05, relative to both saline and sense ODNs control scores).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1994

Diurnal rhythm of galanin-like immunoreactivity in the paraventricular and suprachiasmatic nuclei and other hypothalamic areas.

The peptide galanin (GAL), when injected into the rat hypothalamus, is known to stimulate feeding behavior and affect the secretion of various hormones, including insulin and the adrenal steroid, corticosterone. To determine whether endogenous peptide levels shift in relation to natural rhythms of feeding and circulating hormone levels, rats were sacrificed at different times of the light/dark cycle, and their GAL levels were measured, via radioimmunoassay, in medial hypothalamic dissections and micropunched hypothalamic areas. The results suggest the existence of two distinct diurnal rhythms for hypothalamic GAL. One rhythm, detected exclusively in the area of the SCN, is characterized by bimodal peaks of GAL, threefold higher than basal peptide levels, around the onset of the dark and light periods. The second rhythm shows a single peak of GAL towards the middle of the nocturnal feeding cycle, specifically between the third and sixth hour. This latter rhythm is evident in the dorsal region of the medial hypothalamus, localized specifically to the lateral portion of the PVN. Moreover, it is inversely related to circulating insulin but unrelated to the adrenal steroids, suggesting a possible association between this pancreatic hormone and GAL in the PVN.

Aldosterone↗
PubMed1993

Neuropeptide Y in the arcuate nucleus is modulated by alterations in glucose utilization.

This study examined the response of hypothalamic neuropeptide Y (NPY) to specific metabolic challenges. After intraperitoneal administration of 2-deoxy-D-glucose, which blocks glucose utilization, NPY levels measured via radioimmunoassay were significantly potentiated in the arcuate (ARC) and suprachiasmatic nuclei of the rat hypothalamus. The antimetabolite mercaptoacetate, in contrast, which blocks fatty acid oxidation, produced no significant change and actually tended to reduce NPY levels in the ARC. It is concluded that glucose utilization, in particular, may constitute an important signal, either direct or indirect, in the modulation of NPY production in the hypothalamus.

Animals↗
PubMed1993

Multidimensional assessment of mental state in occupational health care--combined application of three questionnaires: Tokyo University Egogram (TEG), Time Structuring Scale (TSS), and Profile of Mood States (POMS).

We attempted to develop a brief test battery to assess mental state for use in occupational health care settings. As a first step, we focused on the following three psychosocial aspects: ego state, behavioral pattern, and mood state which were considered to be closely related to mental state. To evaluate these parameters, we selected three established self-rating questionnaires: the Tokyo University Egogram for ego state, the Time Structuring Scale for behavioral pattern, and the Profile of Mood States for mood state. The combination of these three questionnaires was applied on 300 healthy company employees and school teachers (170 males and 130 females). Five ego-state factors (Critical Parents, Nurturing Parents, Adult, Free Child, and Adapted Child), five behavioral pattern factors (Withdrawal, Rituals and Pastimes, Activities, Intimacy, and Games), and six mood state factors (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment) were scored. Of 85 correlations between test factors, 49 in males and 61 in females were not significant, indicating that each test in this battery assessed aspects of mental state rather independent of those assessed by the others. However, significant correlations (P < 0.05) were observed for remaining pairs of test factors, indicating that these three parameters were also interrelated with each other, indicating that mental state could be elucidated more comprehensively by assessing all three psychosocial parameters than by assessing only one. The possibility that this battery could be used in the future in worksite health promotion programs is discussed.

Adult↗
PubMed1993

Glucose utilization rates in single neurons and neuropil determined by injecting nontracer amounts of 2-deoxyglucose.

A nontracer amount of 2-deoxyglucose (DG) was intravenously injected into rats, which were frozen 2 and 4 min later in liquid nitrogen. The freeze-dried samples of cell bodies of anterior horn cells, dorsal root ganglion cells, and cerebellar Purkinje cells, as well as the neuropil adjacent to anterior horn cell bodies, were prepared. Their contents of glucose, glucose 6-phosphate, DG, and 2-deoxyglucose 6-phosphate were microassayed using an enzymatic amplification reaction. NADP cycling. Based on the resulting data and theoretical equations previously described, glucose utilization rate (GUR) and apparent distribution volumes (DVs) of glucose and DG were determined. Anterior horn cell bodies had the highest GUR and their neuropil the lowest, although apparent DVs of glucose and DG were similar in both. This indicates that the glucose supply was equally balanced in all, but that the cell bodies had higher functional activity supported by hexokinase (and other enzymes) related to their energy demands. Dorsal root ganglion cells showed the lowest 2-deoxyglucose 6-phosphate formation rate, but their GUR was slightly higher than that of neuropil because of their markedly large DV of glucose, thus demonstrating that the abundant glucose supply supports the neuronal function. Purkinje cells indicated GUR and apparent DVs similar to molecular and granular layers.

Animals↗
PubMed1992

Microdetermination of 2-deoxyglucose and 2-deoxyglucose 6-phosphate to determine glucose utilization rates in single neurons and small CNS regions after injecting nontracer amounts of 2-deoxyglucose.

A nontracer amount (0.25 mmol/kg of body weight) of 2-deoxyglucose (DG) was intravenously injected into rats, which were frozen 2 and 4 min later in liquid nitrogen. Freeze-dried samples of CNS regions and cell bodies of spinal motor neurons were prepared, and the concentrations of glucose, glucose 6-phosphate, DG, and DG 6-phosphate (DG6P) in them were microassayed after 3,000-1,500,000-fold amplification using an enzymatic amplification reaction, NADP cycling. Based on the time course of glucose, DG, and DG6P concentrations in arterial plasma and the anterior horn of the spinal cord, the Sokoloff-type rate equations for DG and DG6P concentrations were mathematically solved, and the resultant DG and DG6P concentration functions were fitted to the data points using the nonlinear least-squares fitting SALS package program. This fitting provided four rate constants for the functions and supported the theoretical basis for our calculations of glucose utilization rate (GUR) when DG was administered in nontracer amounts. The GUR was highest in the spinal motor neurons and lowest in the white matter of the cerebellum. Neuron-rich structures, such as the cerebellar molecular and granular layers and the anterior horn of the spinal cord, had higher GUR values than the white matter of the cerebellum and spinal cord.

Animals↗
PubMed1989

One-step and two-step fluorometric assay methods for general aminotransferases using glutamate dehydrogenase.

One-step and two-step assay methods were developed for general aminotransferases (ATs) utilizing Glu and alpha-ketoglutarate (alpha-KG) as the donor and acceptor of the amino group, by coupling a glutamate dehydrogenase (GDH) reaction with the AT reactions. For instance, alpha-KG formed from Glu by AspAT is reduced and aminated back to Glu by GDH, which oxidizes NADPH corresponding to the amount of alpha-KG formed. In the reverse reaction, Glu formed from alpha-KG is oxidized and deaminated back to alpha-KG by GDH, which reduces NADP+ corresponding to the amount of Glu formed. In the one-step assay, both AT and GDH reactions are simultaneously carried out, and the decrease or increase in NADPH fluorescence is directly monitored in 1.0 ml of the reaction mixture for both forward and reverse reactions. In the two-step assay, an AT reaction is carried out and stopped once at the first step. Next, the alpha-KG or Glu formed is determined fluorometrically in a GDH reaction. In order to analyze partially purified or crude samples, the one-step assay is convenient for surveying the relative activities. The two-step assay is useful for analyzing the properties of enzymes and measuring activities under conditions approaching the optimum. AspAT can be replaced by other general ATs using enzyme-specific substrates in place of oxalacetate and Asp in the assay mixture. The present methods were successfully applied to four enzymes (Asp, alanine, gamma-aminobutyrate, and ornithine ATs) in tissue homogenates and a mitochondrial extract.

Animals↗