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Biomedical subjects

A Morimoto

Publications and source records attributed to A Morimoto.

At least 145 records · Page 8Linked to original sources
PubMed1988

Simultaneous determination of vitamin K1, vitamin K1 2,3-epoxide and menaquinone-4 in human plasma by high-performance liquid chromatography with fluorimetric detection.

A highly sensitive method for measuring endogenous vitamin K1, menaquinone-4 (which is one of the K2 vitamins) and vitamin K1 2,3-epoxide in human plasma was developed, based on high-performance liquid chromatography with coulometric reduction and fluorimetric detection, following extraction from plasma and purification on a Sep-Pak silica cartridge. The detection limits of vitamin K1, menaquinone-4 and vitamin K1 2,3-epoxide were 5, 5 and 8 pg per injection for the standard substances and 30, 30 and 50 pg/ml in human plasma, respectively.

Adult↗
PubMed1988

Ventromedial hypothalamus is highly sensitive to prostaglandin E2 for producing fever in rabbits.

1. The febrile responses induced by intraventricular or intrapreoptic (bilateral) injections of prostaglandin E2 (PGE2) were investigated in the same group of rabbits. Both injections produced dose-dependent fever over a range of 100-2000 ng. However the magnitude of febrile responses induced by ventricular injections was significantly greater than those by intrapreoptic injections. This indicates that there exist regions more sensitive to PGE2 than the preoptic region for producing fever. 2. To explore the regions sensitive to PGE2, the effects of microinjection (1 microliter) of PGE2 (50 and 100 ng) on the rectal temperature were extensively examined in the forty regions of the brain stem. The results showed that the preoptic and anterior hypothalamic region, and the ventromedial hypothalamic region are highly sensitive to PGE2 for producing fever. 3. The febrile responses to PGE2 (50-1000 ng) microinjected into the preoptic region were compared with those induced by injection in the ventromedial hypothalamic region. Fever induced by injection in the ventromedial hypothalamic region was significantly greater than that by injection into the preoptic region. 4. Fever induced by PGE2 injected into the ventromedial hypothalamic region was due to increased heat production in the cold environment (10 degrees C), while in 24 degrees C environment heat losses were reduced without significant changes in heat production. 5. The present results show that the ventromedial hypothalamic region is the most sensitive region to PGE2 for producing fever.

Animals↗
PubMed1988

Multiple control of fever production in the central nervous system of rabbits.

1. The effects of microinjection of prostaglandin D2, E2 and F2 alpha and of endogenous pyrogen on the rectal temperature of rabbits were extensively examined in sixty-eight brain regions and in the third cerebral ventricle. 2. Intracerebroventricular injection of both prostaglandins E2 and F2 alpha produced dose-dependent fever over a range of 100-1000 ng. The selective brain regions, the nucleus broca ventralis, preoptic area, anterior hypothalamus and the ventromedial hypothalamus, responded to microinjections of a small dose (less than 200 ng) of prostaglandins E2 and F2 alpha by producing fever. Furthermore, the lateral hypothalamus, ventral thalamus, substantia nigra and the trigeminal nucleus were also sensitive to high concentrations of prostaglandins E2 and F2 alpha, fever being produced. It is likely that prostaglandin D2 is not involved in fever induction. 3. The ventricular injection of endogenous pyrogen also produced fever. However, brain regions sensitive to microinjection of endogenous pyrogen were exclusively localized to regions near the organum vasculosum laminae terminalis (OVLT), such as the nucleus broca ventralis and the preoptic area. In contrast to the monophasic fever induced by prostaglandins E2 and F2 alpha, about 30 min after ventricular or cerebral injection of endogenous pyrogen the rectal temperature gradually started to rise and the fever was prolonged over 4 h. 4. We investigated the effect of an inhibitor of prostaglandin synthesis, sodium salicylate, on biphasic fever induced by intravenous injection of bacterial endotoxin. The microinjections of sodium salicylate into the bilateral regions near the OVLT suppressed the second peak but had no effect on the first peak. 5. The present study clarifies that there exist two separate mechanisms of induction of biphasic fever. Correlating with the first peak of biphasic fever, prostaglandins synthesized outside the blood-brain barrier act on multiple sites in the central nervous system to induce fever. Correlating with the second peak, endogenous pyrogen acts on regions near the OVLT to synthesize and release pyrogenic prostaglandins.

Animals↗
PubMed1988

Is the central arachidonic acid cascade system involved in the development of acute-phase response in rabbits?

1. In the present study, endogenous pyrogen (EP), prostaglandin E2 or arachidonic acid was injected into the cerebral ventricle to investigate whether central arachidonic acid metabolites are involved in the development of the acute-phase response. The central effects of a cyclo-oxygenase inhibitor, indomethacin, and of a lipoxygenase inhibitor, nordihydroguairetic acid (NDGA), on the acute-phase response induced by an intracerebroventricular injection of EP were also examined. 2. The ventricular injection of EP decreased the plasma concentrations of iron and zinc, while increasing those of copper and fibrinogen and the circulating leucocyte count. However, ventricular injection of prostaglandin E2 affected neither of them, indicating that prostaglandin E2 does not contribute to the acute-phase response production by itself. 3. Both the ventricular injections of indomethacin and NDGA had no effect on the changes in the plasma concentrations of iron, copper and fibrinogen which were induced by ventricular injection of EP. In addition, when arachidonic acid was administered into the cerebral ventricle, the changes in the plasma levels of iron, copper and fibrinogen were not induced. 4. In contrast, EP-induced hypozincaemia was observed upon pre-treatment with NDGA, but not upon pre-treatment with indomethacin. However, plasma zinc increased after the ventricular injection of arachidonic acid. Ventricular injection of EP alone and of EP with NDGA increased the number of circulating leucocytes 8 and 24 h after the ventricular injection, while ventricular injections of arachidonic acid, and of EP with administration of indomethacin induced leucocytosis 8 h after injections. 5. These results suggest that arachidonic acid metabolites do not participate in the genesis of the acute-phase response.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗
PubMed1988

Changes in hypothalamic temperature modulate the neuronal response of the ventral thalamus to skin warming in rats.

1. The influence of hypothalamic temperature on the activity of warm-excited neurones, which responded to skin warming with an increased firing rate, in the ventro-basal (VB) complex of the thalamus of rats was examined electrophysiologically. 2. The warm-excited neurones were classified into three types: hypothalamus-cold neurones in which the firing rate increased with hypothalamic cooling, hypothalamus-warm neurones in which the firing rate increased with hypothalamic warming and hypothalamus-insensitive neurones in which the firing rate was not affected by hypothalamic temperature. The majority of hypothalamus-cold and hypothalamus-warm neurones increased their firing rate at hypothalamic temperature below and above 38 degrees C, respectively. 3. The threshold temperature at which hypothalamus-warm neurones responded to skin warming was lowered by hypothalamic warming. However, hypothalamus-cold neurones responded to lower skin temperatures during hypothalamic cooling. 4. These results show that the neuronal activity of the VB complex in the thalamus, responding to skin warming, is affected by hypothalamic temperature. Thus thermal information from the peripheral thermoreceptors is modulated by hypothalamic temperature at the level of the relay nuclei of the thalamus.

Action Potentials↗
PubMed1988

Effect of prostaglandin E2 on thermoresponsive neurones in the preoptic and ventromedial hypothalamic regions of rats.

1. We investigated the effect of microinjection of prostaglandin E2 (PGE2) into the preoptic (POA) or the ventromedial hypothalamic (VMH) region on rectal temperature in rats. Fever was induced by microinjection of PGE2 into the POA or the VMH regions. The febrile responses induced by PGE2 injected into the VMH region were significantly greater than those induced by injection into the POA region. 2. The effect of temperature on neuronal activity in the POA and the VMH regions was investigated by using slice preparations from rats. It was revealed that there exist many thermoresponsive neurones in the VMH region as well as in the POA region, and that the proportion of thermoresponsive neurones out of the total neurones examined in the VMH region was almost identical to that in the POA region. In addition, the warm-responsive neurones in the VMH region exhibited larger thermal coefficients than those in the POA region. 3. When PGE2 was applied in a recording chamber where the tissue slice was perfused, most of the neurones in the VMH region which responded to PGE2 showed a decrease in their firing rate, while those in the POA region showed an increase in their firing rate, regardless of their thermoresponsiveness. In the POA region, PGE2 began to affect the activities of the warm-responsive neurones in the range of 5 x 10(-7) to 7 x 10(-6) M, whereas maximum responses were obtained between the concentrations of 5 x 10(-6) and 5 x 10(-5) M. In the VMH region, PGE2 began to change the activities of the warm-responsive neurones in the range of 5 x 10(-8) to 5 x 10(-7) M, and the maximum effect of PGE2 on the VMH warm-responsive neurones occurred between the concentrations of 8 x 10(-7) and 4 x 10(-5) M. 4. The present results show that neurones exhibit different responsiveness to PGE2 and different sensitivity to PGE2 between the POA and the VMH regions. Nevertheless, microinjection of PGE2 into either the POA or the VMH region produces fever. Therefore, it is suggested that fever is produced by complex neuronal networks in the central nervous system.

Action Potentials↗
PubMed1988

Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins.

To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

Animals↗
PubMed1987

Suppression of antipyretic response in rabbits by intraventricular protein synthesis inhibitor, anisomycin.

Fevers induced by intravenous injection of endogenous pyrogen (EP) and intraventricular prostaglandin E2 (PGE2) were significantly prolonged when protein synthesis inhibitor, anisomycin was administrated intraventricularly 30 min before or 1 hr after injection of EP or PGE2. The present results show that protein synthesis in the central nervous system is involved in the development of antipyresis.

Animals↗
PubMed1987

Restraint induced stress elicits acute-phase response in rabbits.

We investigated whether a restraint induced stress elicits an acute-phase response which includes changes in the plasma trace metals, fibrinogen and the circulating leucocyte count. The present results showed that restraint-stress induces significant increases in the plasma concentrations of copper and fibrinogen and decreases in those of iron and zinc in rabbits, indicating that some of acute-phase response are produced without fever mediated by endogenous pyrogen.

Animals↗
PubMed1987

Evidence for separate mechanisms of induction of biphasic fever inside and outside the blood-brain barrier in rabbits.

1. Intravenous bacterial endotoxin, or endogenous pyrogen, in high concentration both caused biphasic fever in rabbits. In low concentration they produced only the first phase of fever. 2. Subcutaneous indomethacin suppressed the first phase of fever produced by high concentration of intravenous endotoxin or endogenous pyrogen, but not the second phase. 3. Intraventricular cerebral injection of indomethacin reduced the second phase of fever produced by high concentration of intravenous endotoxin or endogenous pyrogen, but not the first phase. 4. Intraventricular cerebral injection of endotoxin or of endogenous pyrogen caused slow monophasic fever. This was suppressed by intraventricular, but not by subcutaneous, indomethacin. 5. It is concluded that the first phase of biphasic fever is caused by pyrogen acting via structures outside the blood-brain barrier, presumably peripheral nerves, and the second phase by pyrogen acting via structures within the blood-brain barrier, presumably hypothalamic neurones.

Animals↗
PubMed1987

Fever induced in rabbits by intraventricular injection of rabbit and human serum albumin.

1. Intraventricular injection of rabbit and human serum albumin, and rabbit endogenous pyrogen produced dose-dependent fevers in rabbits. The pyrogenicity of albumin was less than one-twentieth of the pyrogenicity of endogenous pyrogen. 2. Fevers induced by ventricular albumin were significantly suppressed by intraventricular injection of indomethacin which is a cyclooxygenase inhibitor. In contrast, subcutaneous injection had no effect. 3. Ventricular endogenous pyrogen induced several of the acute phase responses, i.e. decreases in the plasma concentration of iron and zinc, and increases in both the plasma concentration of copper and the white blood cell count. Albumin induced none of these responses. 4. It is concluded that fever induced by ventricular albumin is processed by prostaglandins synthesized within the central nervous system. However, ventricular albumin does not activate the central mechanism to induce acute phase responses.

Animals↗
PubMed1987

Fever and acute phase response induced in rabbits by human recombinant interferon-gamma.

1. Intravenous (I.V.) and intracerebroventricular (I.C.V.) injections of human recombinant interferon-gamma (IFN-gamma) produced dose-dependent fevers in rabbits. The fever induced by I.V. injection was monophasic and the maximum elevation occurred 80-110 min after injection. The fever induced by I.C.V. injection was observed from about 20 min after injection and was remarkably prolonged over 4 h. 2. The development of pyrogenic tolerance to IFN-gamma was observed when rabbits were given I.V. injections on 3 successive days. Furthermore, the pyrogenicity of IFN-gamma was significantly attenuated by heating at 60 degrees C for 40 min. The I.V. injection of IFN-gamma enhanced the febrile response induced by endotoxin but had no effect on that induced by endogenous pyrogen. 3. The I.V. injection of a large dose of IFN-gamma (6 x 10(6) units/kg) induced an acute phase response, which included a reduction in plasma concentration of iron and zinc. 4. The present results suggest that IFN-gamma released from lymphocytes is one of the endogenous mediator proteins responsible for producing fever and acute phase response.

Acute-Phase Reaction↗
PubMed1987

Separate mechanisms inside and outside the blood-brain barrier inducing metabolic changes in febrile rabbits.

1. We investigated the acute phase response induced by either intravenous (I.V.) or intracerebroventricular injections of bacterial endotoxin or endogenous pyrogen. These caused either monophasic or biphasic fever, and the response includes changes in plasma concentration of iron, zinc, copper, fibrinogen and in circulating leucocyte count.2. The I.V. injection of a small dose of endotoxin or endogenous pyrogen produced a monophasic fever, while a large dose produced a biphasic fever. The ventricular injection of endogenous pyrogen produced a fever similar to the second phase of the biphasic fever.3. The I.V. injection of a small dose of endotoxin or endogenous pyrogen produced a low plasma zinc 8 h after injection, while the ventricular injection of endogenous pyrogen produced a low plasma zinc 24 h after injection. The I.V. injection of a large dose of endotoxin or endogenous pyrogen induced a low plasma zinc 8 and 24 h after injection, suggesting that the hypozincaemia induced by the large dose was mediated by both peripheral and central action of endogenous pyrogen with different time courses.4. The I.V. injection of the small dose did not affect the level of the plasma copper concentration but the I.V. injection of the large dose and the ventricular injection increased it 24 h after injection. It is considered that the plasma copper concentration is mainly controlled by the central action of endogenous pyrogen.5. The changes in the plasma iron and fibrinogen concentration and the circulating white blood cell count induced by the different doses and by the different routes showed very similar patterns, indicating that these are simultaneously controlled by both peripheral and central actions of endogenous pyrogen.6. The present results show that there are two separate mechanisms involved in the acute phase response, one inside and one outside the blood-brain barrier. From the consideration that endogenous pyrogen released from the phagocytic leucocytes induces fever and acute phase response by its action on both the peripheral target organs and the central nervous system, it is suggested that endogenous pyrogen acts both centrally and peripherally, in the same manner as other hormonal agents such as corticosteroids.

Journal Article↗
PubMed1987

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.

We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.

Animals↗
PubMed1987

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in guinea pig brain slices.

To investigate the direct effects of endogenous pyrogen (EP) and prostaglandin E2 (PGE2) on the activity of neurons in the preoptic and anterior hypothalamic (PO-AH) region, single-unit activity was recorded from brain tissue slices prepared from the PO-AH region of guinea pigs. When EP was applied into the perfusate 18% of warm-responsive neurons decreased their activity, and 23% of warm-responsive neurons increased their activity. Most of the thermally insensitive neurons did not respond to EP. PGE2 inhibited 29% of warm-responsive neurons and facilitated 15% of them. Moreover, when EP and PGE2 were applied to the same neurons at different times, the same directions of changes in neuronal activity were observed in 72% of total neurons examined. These results suggest that EP and PGE2 change the neuronal activity of the thermoresponsive neurons in the PO-AH region involved in fever induction. However, by these results, the direction of neuronal response induced by these substances could not be generally categorized based on the thermoresponsiveness of the individual neuron.

Animals↗
PubMed1987

Effect of PGE2 on preoptic and anterior hypothalamic neurons using brain slice preparation.

In the present study, effects of prostaglandin (PG) E2 on the hypothalamic neurons were investigated using slice preparations of rats. Warm- (57%) and cold-responsive (33.3%) and thermally insensitive (42.3%) neurons were facilitated by PGE applied in a culture chamber. Some neurons (5.1%) showed inhibitory response to PGE2. The remaining neurons did not show any responsiveness to PGE2. Moreover, we also examined the effects of PGE2 on the hypothalamic neurons both in normal Krebs-Ringer solution and synaptic blocking medium (low Ca2+, high Mg2+). Most of the neurons (12/15) retained their responsiveness to PGE2 in the synaptic blocking medium, indicating that PGE2 has a direct action on the hypothalamic neuron. Therefore, it is conceivable that neurons in the preoptic and anterior hypothalamic region that respond to PGE2 might play an important role in the development of fever. However, characteristics of neurons responding to PGE2 were not determined based on their thermoresponsiveness.

Animals↗