Biomedical subjects

H Yoshimatsu

Publications and source records attributed to H Yoshimatsu.

At least 73 records · Page 4Linked to original sources

PubMed1994

Hypothalamic neuronal histamine regulates feeding circadian rhythm in rats.

To clarify involvement of hypothalamic neuronal histamine in feeding circadian rhythm, we analyzed rat behavioral patterns using chemical probes which affect endogenous histaminergic activity. Sustained infusion of alpha-fluoromethylhistidine (FMH), a specific suicide inhibitor of a histamine-synthesizing enzyme, into the rat third cerebral ventricle disrupted light-dark cycles of feeding, drinking, and ambulatory behavior. Food and water intake and ambulatory activity during the 12-h light period increased, and those during the 12-h dark period decreased after the infusion. The ratio of the light period to the 24-h total period (L/T ratio) increased in all behavioral parameters. Assessed by 3-h cumulative analysis, amplitudes of circadian rhythmicity decreased in all behavioral parameters, whereas only the acrophase of ambulatory activity shifted forward after FMH infusion. Chlorpheniramine, an H1-antagonist, selectively increased food intake during the light and decreased it during the dark period. Consequently, the antagonist increased the L/T ratio in food intake, but did not affect the ratio in water intake or ambulatory activity. Famotidine, an H2-antagonist, did not affect the ratio in any parameter. Thioperamide, an antagonist of auto-inhibitory effects on histamine synthesis and release at presynaptic H3-receptor sites, decreased food intake during the dark, but did not affect the L/T ratio in any parameter. These findings indicate that neuronal histamine may regulate feeding circadian rhythm through the hypothalamic histamine H1-receptor in rats.

Animals↗

PubMed1994

A physiological role of brain histamine during energy deficiency.

Histaminergic activation in the rat hypothalamus was investigated under a deficit in energy supply. Fasting of rats for 24 h increased hypothalamic histamine (HA) content. Intraperitoneal (IP) injection of insulin (2 U/kg) increased pargyline-induced accumulation of tele-methylhistamine (t-MH) leaving steady-state HA and t-MH levels unaffected, which implies enhancement of HA turnover rate. The insulin infusion induced hypoglycemia both in rats with and without pargyline pretreatment. Infusion of 2-deoxy-D-glucose (2-DG) into the third cerebroventricle also produced an increase in pargyline-induced accumulation of t-MH and no change in steady-state HA and t-MH levels. The 2-DG infusion induced hyperglycemia. Hypothalamic glycogen content decreased after 24 h starvation, but this decrease was prevented by depletion of HA by alpha-fluoromethylhistidine. Absolute glycogen contents in the cortex were lower than those in the hypothalamus, and were not affected by fasting or depletion of HA. The results indicate that activation of hypothalamic HA in response to glucoprivation may modulate homeostatic control of energy supply in the brain.

Animals↗

PubMed1994

Thermoregulation and hypothalamic histamine turnover modulated by interleukin-1 beta in rats.

To clarify the involvement of hypothalamic histamine in thermogenic response provoked by high ambient temperature, or interleukin-1 beta (IL-1 beta), changes in rectal temperature and histamine turnover were investigated. Rectal temperature was maintained normally after exposure to high ambient temperature, but elevated by IL-1 beta. In spite of these different responses of body temperature, hypothalamic histamine turnover was increased in each treatment. The results suggest that hypothalamic histaminergic neurons are activated not only peripherally by high ambient temperature, but also centrally by IL-1 beta as endogenous pyrogen.

Animals↗

PubMed1994

Neuronal glucoprivation enhances hypothalamic histamine turnover in rats.

Histamine (HA) turnover in the rat hypothalamus following insufficient energy supply due to glucoprivation was examined after administration of insulin or 2-deoxy-D-glucose (2-DG). HA turnover was assessed by accumulation of tele-methylhistamine (t-MH), a major metabolite of brain HA, following administration of pargyline. Intraperitoneal injection of 1, 2, and 4 U/kg of insulin, which had no influence on steady-state levels of HA and t-MH, increased pargyline-induced accumulation of t-MH. Accumulation of t-MH due to pargyline was inversely related to the concomitant plasma glucose concentration after different doses of insulin. The level of t-MH accumulated by pargyline did not change compared with that of controls, when a euglycemic condition was maintained or insulin at a dose of 6 mU per rat was infused into the third cerebroventricle. Intracerebroventricular infusion of 24 mumol per rat of 2-DG, which had no influence on steady-state levels of HA and t-MH, increased the level of t-MH enhanced by pargyline. The results indicate that an increase in hypothalamic HA turnover in response to glucoprivation may be involved in homeostatic regulation of energy metabolism in the brain.

Animals↗

PubMed1994

2-deoxy-D-glucose suppresses food intake through activation of hypothalamic histamine in rats.

The aim of this experiment was to demonstrate whether brain histamine contributes to delayed suppression of food intake after administration of 2-deoxy-D-glucose (2-DG). Food intake decreased significantly for 48 h after infusion of 2-DG into the rat third cerebroventricle. This delayed decrease in food intake was abolished by depletion of neuronal histamine by intraperitoneal pretreatment with alpha-fluoromethylhistidine (160 mumol/rat), a suicide inhibitor of a histamine-synthesizing enzyme. Intracerebroventricular infusion of 24 mumol 2-DG accelerated turnover rate of hypothalamic histamine. These results indicate that the delayed feeding suppression by 2-DG is modulated through histaminergic neurons in the hypothalamus. This histaminergic response may be related, at least in part, to homeostatic control of energy metabolism in the brain.

Animals↗

PubMed1994

[A case of advanced gastric cancer complicated with multiple liver metastasis successfully treated with l-LV and 5-FU combination].

A 65-year-old man complaining of nausea and loss of appetite was diagnosed as having Borrmann type 3 gastric cancer with multiple liver metastasis. He was treated for 5 days with bolus injections of l-leucovorin (l-LV: 100 mg/m2/day) followed by 5-fluorouracil (5-FU; 370 mg/m2/day), and this was repeated every 4 weeks. The computed tomography scan after 3 cycles showed an approximately 70% decrease in the size of metastatic lesions, indicating a partial response. The primary gastric lesion also showed a partial response. There were modest but tolerable side effects such as diarrhea. After 3 cycles, the patient was discharged and was given oral 5-FU preparation. He died 9 months after initial chemotherapy with a response duration of 5 months. This l-LV and 5-FU combination therapy appears useful for advanced gastric cancer.

Aged↗

PubMed1993

Aminoglucose-induced feeding suppression is regulated by hypothalamic neuronal histamine in rats.

Central mechanisms involved in feeding suppression produced by 1-deoxy-D-glucosamine (1-DGlcN) and 1-deoxy-N-acetylglucosamine (1-DGlcNAc) are unclear. To clarify the mechanisms, we investigated the role of hypothalamic neuronal histamine (HA) in feeding suppression induced by 1-DGlcN and 1-DGlcNAc in rats. Food intake was suppressed for 3 days after a single infusion of 24 mumol 1-DGlcN into the third cerebroventricle (i.c.v.). Depletion of presynaptic HA due to intraperitoneal infusion (i.p.) of alpha-fluoromethylhistidine (FMH), a specific inhibitor of the HA synthesizing enzyme histidine decarboxylase (HDC), abolished feeding suppression completely. Blockade of postsynaptic H1-receptors by i.p. injection of 26 mumol chlorpheniramine also abolished the suppression. Oral administration of 2.4 mmol 1-DGlcNAc suppressed food intake. However, depletion of neuronal HA due to FMH did not affect the suppression. I.c.v. infusion of 24 mumol 1-DGlcN increased turnover rate of HA at 1 h after the infusion. Hypothalamic HA concentration, but not that of tele-methylhistamine (t-MH), increased at 24 h after i.c.v. infusion of 1-DGlcN, which suggests a correlation between HA concentration and the behavioral response. These results indicate that 1-DGlcN, but not 1-DGlcNAc, modulates feeding suppression through HA neurons in the hypothalamus. Differences in mechanisms of feeding suppression by these aminoglucoses may depend on the principal sites of action in the brain and/or peripheral organs.

Acetylglucosamine↗

PubMed1993

Glucagon injected in the lateral hypothalamus stimulates sympathetic activity and suppresses monoamine metabolism.

Glucagon injected in the lateral hypothalamus stimulates sympathetic activity and suppresses monamine metabolism. The central hypothesis underlying this study is that there is a reciprocal relationship between food intake and sympathetic activity to IBAT. This hypothesis was tested by using intrahypothalamic microinjections of glucagon, a peptide that has been reported to decrease food intake. Sympathetic nerve activity to interscapular brown adipose tissue (IBAT) was measured as electrophysiological discharges of sympathetic nerves to IBAT. The microinjection of glucagon into the lateral hypothalamus (LH) increased sympathetic nerve activity by +103.8 +/- 35.0% (mean +/- S.E.M.) from pre-injection basal level by 30 min after injection. There was a gradual return to baseline. Micro-injection of glucagon into the LH depressed food intake. Monoamine metabolism was measured by using a microdialysis probe attached to a guide cannula for microinjection of glucagon into the LH. After microinjection of glucagon, the dialysates were collected over 30 min intervals and assayed for norepinephrine (NE), serotonin (5-HT), dopamine (DA) and their metabolites (3-methoxy-4-hydroxyphenylglycol (MHPG); 5-hydroxyindole-3-acetic acid (5-HIAA); and 3,4-dihydroxyphenylacetic acid (DOPAC). Glucagon suppressed both NE and MHPG concentrations in the lateral hypothalamus (LH), and the concentration of DOPAC was also decreased. There was no change of 5-HT concentration but 5-HIAA levels were reduced by glucagon treatment. These data show that glucagon injected in the LH stimulates sympathetic activity and suggest that this may have occurred by suppression of norepinephrine, dopamine and serotonin turnover in the LH of freely moving rats. These data support the hypothesis of a reciprocal relationship between food intake and sympathetic activity.

Adipose Tissue, Brown↗

PubMed1993

Neuronal histamine in the hypothalamus suppresses food intake in rats.

Using probes to manipulate hypothalamic neuronal histamine, we report here that changes in neuronal histamine modulate physiological feeding behavior in rats. Infusion of alpha-fluoromethylhistidine (FMH), a "suicide" inhibitor of histidine decarboxylase (HDC), into the third cerebroventricle induced feeding in the early light phase when the histamine synthesis was most accelerated. FMH at an optimum 2.24 mumol dose elicited feeding in 100% of rats. Treatment of FMH specifically and selectively decreased concentration of histamine without affecting concentrations of catecholamines in the hypothalamus. Immediately before the dark phase, when the histamine synthesis was normally lower, FMH infusion did not affect feeding-related parameters such as meal size, meal duration or latency to eat. Conversely, thioperamide, which facilitates both synthesis and release of neuronal histamine by blocking presynaptic autoinhibitory H3 receptors, significantly decreased food intake after infusion of a 100-nmol dose into the third cerebroventricle. The effect of thioperamide was abolished with i.p. injection of 26 mumol/kg chlorpheniramine, an H1antagonist. FMH at 224 nmol was microinfused bilaterally into the feeding-related nuclei in the hypothalamus. The ventromedial nucleus (VMH) and the paraventricular nucleus (PVN), but not the lateral hypothalamus, the dorsomedial hypothalamus or the preoptic anterior hypothalamus were identified as the active sites for the modulation. Neuronal histamine may convey suppressive signals of food intake through H1 receptors in the VMH and the PVN with diurnal fluctuation.

Animals↗

PubMed1993

Sympathetic nerve activity after discrete hypothalamic injections of L-glutamate.

In these experiments L-glutamate, an amino acid which stimulates neuronal discharge, was microinjected into several hypothalamic nuclei and the resultant changes in electrical firing rate of sympathetic nerves innervating interscapular brown adipose tissue (IBAT) were measured. Three patterns of response were seen. A single large stimulatory response was seen when L-glutamate was microinjected into the ventromedial hypothalamus (VMH). Microinjection of L-glutamate into the paraventricular nucleus (PVN) produced a predominantly stimulatory response which was of smaller magnitude than the VMN. However in three animals L-glutamate in the PVN decreased firing rate and in one animal a biphasic response was observed. The second pattern was a decrease in sympathetic activity to IBAT which was the predominant pattern following injection of L-glutamate into the dorsomedial hypothalamus (DMH). However, a biphasic pattern was also observed. Injection of L-glutamate into the lateral hypothalamic area (LHA) produced 3 patterns of response; an increase, a decrease; or a biphasic response in nearly equal numbers of animals. The predominant response to L-glutamate in the preoptic area (POA) was biphasic. These data are consistent with the hypothesis that the VMH is the predominant stimulatory site for activation of the sympathetic nervous system to IBAT in the rat. The DMH and LHA appear to be the predominant inhibitory areas.

Adipose Tissue, Brown↗

PubMed1993

Ginsenoside Rg1 prevents histaminergic modulation of rat adaptive behavior from elevation of ambient temperature.

Effects of ginsenoside Rg1 (Rg1) on histaminergic modulation of both adaptive behavior and thermoregulation were investigated at high ambient temperature. Continuous infusion of Rg1 using an osmotic minipump into the rat third cerebroventricle attenuated anorexia induced by elevation of ambient temperature from 21 degrees C to 31 degrees C. Intraperitoneal injection of alpha-fluoromethylhistidine (FMH), a specific suicide inhibitor of a histamine synthesizing decarboxylase enzyme, also prevented the anorexia induced by elevated temperature. The ratio of water intake to food intake, which showed no change on the first day after elevation of room temperature, was not influenced by treatment of either FMH or Rg1. Rectal temperature, which was normally maintained at a constant level even after shifting ambient temperature from 21 degrees C to 31 degrees C, elevated after FMH treatment. The Rg1 infusion, however, maintained rectal temperature normally at 31 degrees C. Hypothalamic histamine content increased in response to elevation of ambient temperature. The Rg1 infusion maintained constant histamine level against elevation of environmental temperature. Under the heated condition FMH reduced hypothalamic histamine. These findings suggest that Rg1 may modulate rat adaptive behavior by blockade of temperature-related information into the hypothalamic histamine neurons.

Acclimatization↗

PubMed1993

Abnormalities in obese Zuckers: defective control of histaminergic functions.

Histaminergic functions in the hypothalamus of Zucker obese rats were investigated. Blockade of postsynaptic H1-receptor after infusion of chlorpheniramine into the third cerebroventricle (ICV) failed to affect feeding in obese Zuckers, although feeding was potently elicited in Wistar King A control rats. Presynaptic increase in histamine by an H3-receptor antagonist, thioperamide, suppressed feeding in Wistar controls, but not in obese Zuckers. Under high ambient temperature, Wistar controls decreased food intake and maintained their rectal temperature normally. However, obese Zuckers and histamine depleted rats due to alpha-fluoromethyl-histidine (FMH), a specific "suicide" inhibitor of a histamine synthesizing decarboxylase enzyme (HDC), failed to show this decrease in food intake as adaptive behavior. Their rectal temperature concomitantly elevated in response to heated circumstance. ICV infusion of thioperamide increased the blood glucose level in Wistar controls, but not in obese Zuckers. The defect in all these regulatory functions found in obese Zuckers may be derived from an excessive decrease in hypothalamic histamine content due to inactivity of HDC. The histamine-depleted model sufficiently mimicked the abnormalities in obese Zuckers.

Animals↗

PubMed1993

Food consistency modulates eating volume and speed through brain histamine in rat.

Changes in meal parameters of rats fed with different consistency of food were examined using hard and soft pellets. Meal size and eating speed of the first meal after 1800 h increased significantly in rats fed with soft pellets compared to those fed with hard pellets. Effects of histamine depletion on meals treated with hard or soft pellets were investigated after an intraperitoneal injection of 0.11 mmol/kg alpha-fluoromethylhistidine (FMH), a specific suicide inhibitor of the histamine synthesizing decarboxylase enzyme. When rats were fed with hard pellets, FMH significantly decreased eating speed and prolonged meal duration without affecting meal size. When rats were fed with soft pellets, FMH increased meal size and duration, but not eating speed. The meal parameter of eating speed was significantly decreased and meal size and duration were increased in obese Zuckers, a hereditary histamine-depleted animal model, when compared to their lean littermates. These results indicate that proprioceptive sensation from the oral cavity may regulate meal parameters through histaminergic neurons in the brain.

Animals↗

PubMed1993

Effect of vagotomy on ornithine decarboxylase activity in rat duodenal mucosa.

The aim of this study was to determine whether the circadian rhythm of ornithine decarboxylase (ODC) activity in rat small intestine is controlled by factors other than luminal nutrients. ODC activity in duodenal and jejunal mucosa of rats fed ad libitum was measured at four time points (0500, 1100, 1700, 2300 h; light period: 0800-2000 h). ODC activity in the jejunum increased in the dark period, which is when rats normally eat. In contrast, ODC activity in the duodenum began to increase at 1700 h, which is when rats do not normally eat, as indicated by the recorded feeding pattern. The increase in ODC activity in the duodenum at 1700 h, but not at other time points, was abolished by subdiaphragmatic vagotomy, whereas vagotomy had no effect on the feeding pattern of rats. Subdiaphragmatic vagotomy had no effect on ODC activity in the jejunum. ODC activity in the duodenum increased following glycoprivation of the central nervous system induced by infusion of 2-deoxyglucose into the third cerebroventricle. These results indicate that the increase in duodenal ODC activity at 1700 h is due to a signal from the upper brain structure through the vagal nerve and not to luminal nutrient factors.

Animals↗

PubMed1993

Effect of beta-endorphin on sympathetic nerve activity to interscapular brown adipose tissue.

beta-Endorphin was injected into the third cerebroventricle to investigate its effects on sympathetic nerve activity to interscapular brown adipose tissue (IBAT) in rats. Multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically in anesthetized rats. The intracerebroventricular injection of beta-endorphin (125, 250, and 500 pmol/rat in 10 microliters) suppressed sympathetic nerve activity in a dose-related fashion (-23.9 +/- 20.4, -38.7 +/- 7.1, and -66.7 +/- 7.6% 30 min after injection) compared with preinjection baseline. N-acetyl-beta-endorphin (250 pmol) had no effect on sympathetic nerve activity to IBAT. The intraperitoneal injection of naloxone (5.0 mg/rat) did not affect sympathetic nerve activity, but preinjection of naloxone inhibited the suppressive effect of intracerebroventricular injection of beta-endorphin (250 pmol). We conclude that the intracerebroventricular administration of beta-endorphin suppressed the sympathetic nerve activity to IBAT through opioid receptors. The results of this experiment are consistent with the hypothesis that beta-endorphin has a reciprocal effect on food intake and the sympathetic nervous system.

Adipose Tissue, Brown↗

PubMed1993

Thymectomy in human renal transplantation.

We reviewed 17 patients submitted to thymectomy via the suprasternal notch (Yoshimatsu Method I), which was performed before transplantation in 12 patients and after transplantation in 5 patients. There were no complications of thymectomy. Graft survival of our patients with thymectomy was better than that for the overall allograft survival in Japan transplant registry for the same period. Pathologic studies revealed that involution of the cortex was not observed in 5 thymuses removed from recipients who had thymectomy after transplantation even though 2 of them had received 6.4 g and 3.5 g of prednisolone for 19 months and 32 months, respectively.

Humans↗

PubMed1993

[Alcoholic liver injury accompanied with various metabolic and endocrinological disorders--a case report].

We report a young female case of alcoholic liver injury accompanied with various metabolic and endocrinological disorders. A 29 year-old woman was admitted because of general fatigue and hyperlipidemia. She was a heavy drinker. Laboratory data on admission revealed liver dysfunction and hyperlipidemia (type II b) with a quite high serum gamma-glutamyltranspeptidase (gamma GTP) level. The microscopic finding of the liver biopsy specimen showed fatty metamorphosis and ballooning of hepatocytes, and she was diagnosed as heavy alcoholic liver injury. The endocrinological examination revealed the elevated plasma cortisol level, though the urinary 17-hydroxycorticoids (17-OHCS) and 17-ketosteroids (17-KS) excretion and the plasma adrenocorticotropic hormone (ACTH) level were reduced. Cortisol secretion showed the normal circadian rhythm and the normal response to ACTH provocation. The levels of plasma triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were also reduced. These endocrinological and metabolic disorders were normalized in company with recovery of the liver function by temperance, diet therapy and nutritional education. Thus, these abnormalities were considered to be resulted from the alcoholic liver injury and the effect of the ethanol to the hypothalamic-pituitary system.

Adult↗

PubMed1993

[A case of systemic lupus erythematosus who developed nodular shadows in the lung in parallel with the disease activity].

A 35-year old woman was admitted to our hospital in April 1991 due to the appearance two nodular shadows on chest X-ray. The patient's past medical history was as follows; In 1986, she developed polyarthralgia, facial eruptions and Raynaud's phenomenon which was treated with prednisolone. In 1988, investigations revealed proteinuria where by the diagnosis of SLE complicated with lupus nephritis was established. Subsequently, treatment with cyclophosphamide was carried out. However, in January 1991, there was further increase in urine proteins in accompaniment with systemic eruptions. In addition, laboratory findings showed an increasing titre of anti-DNA antibody and decreasing serum compliments. In April 1991, as indicated before, a chest X-ray revealed nodular shadows in the right upper and lower lung fields, therefore, a transbronchial lung biopsy was performed. The histology revealed inflammatory infiltrates in the bronchoalveolar tissue, fibrosis of the septa- and exudates in the alveolar space. These findings suggested fibrosing alveolitis. It was true considered that these lesions in the lung were associated with the exacerbation of SLE. In view of this, the dose of prednisolone was increased to 60 mg/day. Consequently, the nodular shadows regressed and the clinical course of SLE improved. It is well appreciated that some patients with SLE develop variable pulmonary involvement, however, this case is of great interest due to the fact that multiple nodular shadows on chest X-ray are very rare in SLE.

Adult↗