Biomedical subjects
Publications and source records attributed to A Morimoto.
In the present study, we tried to examine whether the 2-deoxy-D-[14C]glucose (2-DG) technique is useful to investigate the metabolic activity of fetal rat brain in the maternal uterus. The result shows that metabolic mapping of the fetal brain was clearly obtained by means of the 2-DG technique.
We investigated the effect of intracarotid infusion of prostaglandin E2 (PGE2) on the single-unit activity of neurons in the preoptic and anterior hypothalamic (PO/AH) region. A total of 35 neurons in the PO/AH region were examined: 10 were warm-responsive neurons, 6 were cold-responsive neurons, and 19 were thermally insensitive neurons. In the warm-responsive neurons, the activities of 4 neurons were facilitated, while 3 neurons were inhibited and 3 neurons were not affected after intracarotid infusion of PGE2. In the cold-responsive neurons, the activities of 2 neurons were facilitated and 4 neurons were not affected by PGE2 infusion. Furthermore, 15 out of 19 thermally insensitive neurons were not affected by PGE2 infusion. These results suggest that thermoresponsive neurons of the PO/AH region respond well to intracarotid infusion of PGE2, compared with thermally insensitive neurons. However, the direction of neuronal response induced by intracarotid infusion of PGE2 could not be generally categorized based on the thermoresponsiveness of individual neurons.
1. Thermoregulation against cold exposure was studied in rats during pregnancy and early lactation, and compared with that of virgin rats. 2. When exposed to 0 degrees C for 60 min, rats which were within 24-48 h of parturition (pre-1-day rats) and those within 24 h of parturition (pre-0-day rats) showed significantly larger falls of colonic temperature (Tco) than virgin rats. The temperature decrease was greatest in the pre-0-day rats, being 4.1 +/- 0.4 degrees C (mean +/- S.E.M.) at the end of cold exposure, compared with a decrease of 1.7 +/- 0.3 degrees C in the virgin rats. The tail skin temperature fell to 0 degrees C during cooling in all virgin rats and in pregnant rats at each gestational stage. 3. During cold exposure at 10 degrees C for 30 min, pre-0-day rats also showed significantly larger falls in Tco (1.8 +/- 0.6 degrees C) than virgin (0.4 +/- 0.2 degrees C), pre-1-week (0.8 +/- 0.3 degrees C), post-0-day (0.3 +/- 0.3 degrees C) or post-1-week rats (0.4 +/- 0.3 degrees C). Although body weights in pre-0-day rats were far larger than those in virgin rats, the increase in oxygen consumption per animal during cold exposure was 50% lower in pre-0-day rats (2.2 +/- 0.5 ml/min) than in virgin rats (5.3 +/- 0.3 ml/min). There was no difference in basal oxygen consumption per animal between the late pregnant and virgin rats. 4. Within 24 h after parturition, both the decrease of Tco and the increase of oxygen consumption during cold exposure returned to the values observed in virgin rats. 5. The present results demonstrate clearly that cold-induced thermogenesis is significantly suppressed in rats at a late stage of pregnancy.
1. We investigated the effect of intravenous, intracerebroventricular and intrapreoptic injections of human recombinant granulocyte colony stimulating factor (GCSF) on body temperature and acute phase responses in the rabbit, including changes in the plasma concentration of iron, zinc, copper and fibrinogen and in circulating leucocyte count. 2. Neither intravenous nor intracerebroventricular injection of GCSF had any effect on the body temperature. 3. Both the intravenous and the intracerebroventricular injections of GCSF induced a dose-dependent increase in the circulating leucocyte count but neither affected the plasma concentration of iron, zinc, copper and fibrinogen. Furthermore, intrapreoptic injection of GCSF produced leucocytosis but had no effect on the red blood cell count. 4. The present results suggest that GCSF induces leucocytosis through its action on both the peripheral target organs and the central nervous system.
1. Febrile responsiveness of rabbits and rats to intravenous (I.V.) or intracerebroventricular injection of human recombinant interleukin-1 alpha (IL-1 alpha), human recombinant interleukin-1 beta (IL-1 beta) and prostaglandin E2 was examined. 2. The I.V. injection of both IL-1 alpha and IL-1 beta produced dose-dependent fever over a range of 0.05-2.0 micrograms/kg. A small dose of IL-1 alpha (0.5 micrograms/kg) or IL-1 beta (0.5 micrograms/kg) produced a monophasic patterned fever in both rabbits and rats. A large dose (2.0 micrograms/kg) of IL-1 alpha or IL-1 beta produced a biphasic fever in rabbits, but monophasic fever in rats. Febrile responses in rabbits induced by I.V. injection of IL-1 alpha or IL-1 beta were significantly greater than those in rats induced by these same injections. Furthermore, in both species, the pyrogenicity of I.V. IL-1 beta was greater than that of IL-1 alpha. 3. The intracerebroventricular injection of both IL-1 alpha and IL-1 beta produced dose-dependent fever over a range of 0.2-20 ng. In rabbits and rats, the ventricular injections of IL-1 alpha and IL-1 beta produced fever with almost the same pattern--monophasic, regardless of injection doses. Although febrile responsiveness of rabbits to ventricular injection of IL-1 alpha was greater than that of rats, responsiveness to IL-1 beta was almost the same in both species. Pyrogenicity of ventricular IL-1 beta was greater than that of IL-1 alpha. However, febrile responses in rats induced by ventricular injections of several doses (2-2000 ng) of prostaglandin E2 were greater than those in rabbits. 4. The present results show that febrile responsiveness of rabbits to I.V. IL-1 is significantly greater than that of rats. However, fever sensitivity within the central nervous system (CNS) of rats is not lower compared with that of rabbits. Therefore, we considered that between the two species there exist structural differences in the organum vasculosum laminae terminalis (OVLT), which is currently believed to be the pathway of pyrogen to the CNS and/or the site of production of pyrogenic prostaglandins. 5. Histological examinations showed that the rabbit's OVLT has two vascular components with capillaries, one in the layer near the third ventricle and the other in the layer near the subarachnoideal space. However, the rat's OVLT only has a single component, in the layer near the subarachnoideal space.(ABSTRACT TRUNCATED AT 400 WORDS)
1. We investigated the effect of physical training on febrile and acute-phase responses induced in rats by intravenous (I.V.) injection of bacterial endotoxin or human recombinant interleukin-1 beta (IL-1). Physical training was performed by swimming for 1 h per day, 5 days a week. After four weeks of training, animals were used in the experiments. 2. The I.V. injection of endotoxin produced a febrile response in the trained group but not in the control group. However, there were no statistically significant differences between febrile responses induced by the I.V. injection of IL-1 in the control and trained groups. 3. The I.V. injection of endotoxin significantly decreased the plasma concentration of iron and zinc and increased the plasma fibrinogen concentration in both the control and the trained groups. However, the decreases in the plasma iron and zinc concentrations in the trained group were significantly greater than those in the control group. The I.V. injection of endotoxin increased the circulating leucocyte count in the only trained group. 4. The I.V. injection of IL-1 significantly decreased the plasma concentration of iron and zinc and increased the plasma fibrinogen concentration and the circulating leucocyte count in both the control and the trained groups. However, between the two groups, no significant differences in the values of acute-phase reactants were observed. 5. The present results suggest that the ability to produce cytokine(s) to induce febrile and acute-phase responses is enhanced by physical training. However, physical training has no effect on the febrile and acute-phase responses induced by IL-1.
After rats were chronically exercised by endurance swimming, an augmentation of succinic dehydrogenase (SDH) activity in the diaphragm and the EDL muscle was observed. In addition, endurance training induced a decrease in the percentage of myosin heavy chain (MHC) IIb in the diaphragm, and a decrease in the percentage of HCIIb concomitant with an increase in the percentage of HCIId in the EDL muscle. These results indicate that endurance training induced not only an increase of the oxidative capacity but also an alteration in the expression of an MHC phenotype in the diaphragm and skeletal muscle.
A highly sensitive method for measuring endogenous phylloquinone and menaquinones in animal tissues was developed, based on high-performance liquid chromatography with coulometric reduction and fluorimetric detection, following extraction from tissue homogenate and purification on a Sep-Pak silica cartridge followed by thin-layer chromatography. The detection limits of phylloquinone, menaquinone-4, -6, -10 and -13 were 40, 40, 50, 70 and 80 pg/g in rat liver, respectively.
1. Intravenous (I.V.) injection of human recombinant interleukin-1 alpha (IL-1 alpha) produced dose-dependent monophasic fevers in rats. Moreover, the I.V. injection of IL-1 alpha produced dose-dependent rises in the plasma concentrations of adrenocorticotrophic hormone (ACTH) 30 min after injections with dosages of 5 micrograms/kg and 15 micrograms/kg of IL-1 alpha. 2. The febrile responses induced by the I.V. injection of IL-1 alpha (15 micrograms/kg) were completely abolished, and conversely hypothermia occurred, when the animals were pre-treated with a cyclo-oxygenase inhibitor, indomethacin (INDO). Pre-treatment with INDO also inhibited the increase in the plasma concentrations of ACTH induced by I.V. injection of IL-1 alpha (15 micrograms/kg), indicating that enhancement of plasma concentrations of ACTH induced by I.V. injection of IL-1 alpha is processed through the action of prostaglandins. 3. Intrapreoptic injection of prostaglandin E2 produced a dose-dependent fever with a rapid onset at doses of 25 and 100 ng. Moreover, the intrapreoptic injection of prostaglandin E2 increased the plasma concentrations of ACTH in a dose-dependent manner 30 min after injections. 4. The intrapreoptic injection of IL-1 alpha (20 ng) caused slow monophasic fever. However, no significant elevation of plasma concentrations of ACTH was observed 30, 90 and 180 min after the intrapreoptic injection of IL-1 alpha, as compared with the ACTH levels at each time in the control group which received an intrapreoptic injection of saline. 5. These results suggest that intrapreoptic prostaglandin E plays an important role in the ACTH response by inducing the release of corticotrophin-releasing factor (CRF).
1. The effects of microinjection of rabbit endogenous pyrogen and human recombinant interleukin-1 alpha on rectal temperature and acute phase responses were extensively examined in forty different brain regions of rabbits. The acute phase responses that were investigated were the changes in plasma levels of iron, zinc and copper concentration and the changes in circulating leucocyte count. 2. The rostral hypothalamic regions, such as nucleus broca ventralis, preoptic area and anterior hypothalamic region, responded to the microinjection of endogenous pyrogen or interleukin-1 by producing both fever and acute phase responses. 3. The microinjection of endogenous pyrogen or interleukin-1 into the rostral hypothalamic regions significantly decreased the plasma levels of iron and zinc concentration 8 and 24 h after injection. The circulating leucocyte count increased 8 h after injection. However, neither the injections of endogenous pyrogen nor interleukin-1 affected the number of red blood cells. 4. The present results show that the rostral hypothalamic regions respond directly to endogenous pyrogen or interleukin-1 with the consequent development of fever and acute phase responses.
We investigated the effect of human recombinant interleukin 1 alpha (hrIL-1 alpha) and human recombinant tumor necrosis factor (hrTNF) on body temperature and acute-phase response, including changes in the plasma concentration of iron, zinc, and copper and in circulating leukocyte count. The intravenous injection of a smaller dose of either hrIL-1 alpha (0.5 micrograms/kg) or hrTNF (2 micrograms/kg) produced a monophasic fever, whereas a larger dose (hrIL-1 alpha, 2 micrograms/kg; hrTNF, 10 micrograms/kg) produced a biphasic fever. The intracerebroventricular injection of hrIL-1 alpha or hrTNF produced a dose-dependent fever. The intravenous injection of either hrIL-1 alpha or hrTNF decreased the plasma concentration of iron and zinc and increased the plasma copper concentration and the circulating leukocyte count. The intracerebroventricular injection of hrIL-1 alpha induced those responses, although the intracerebroventricular injection of hrTNF did not. The present results show that two kinds of monokines, hrIL-1 alpha and hrTNF, are intrinsically pyrogenic and induce the acute-phase response. Furthermore, it is suggested that hrIL-1 alpha induces febrile and acute-phase responses through its action on both the peripheral target organs and the central nervous system. However, hrTNF induces those responses only by its action on the peripheral target organs outside the blood-brain barrier.
The responses of rat thalamic neurons to skin cooling were electrophysiologically examined. The responses of cold-excited neurons were classified into two types. One is a steplike response in which the activity abruptly increases with skin cooling, and the other is a graded response in which the activity gradually increases with skin cooling. The sites of these neurons were histologically identified in the ventrobasal complex of the thalamus, ventrolateral thalamus, and posterior thalamus. Two-thirds of them were found in a marginal region of the ventrobasal complex. There is no specific localization between the sites of thalamic neurons showing the steplike response and those showing the graded response. Furthermore, the effects of hypothalamic temperature on the thalamic neurons responding to skin cooling were observed. The response of thalamic neurons to cold stimulation of the skin was markedly suppressed during the hypothalamic warming. These results show that the steplike response is related to converting thermal analog signals to digital signals and that the graded response is related to relaying analog patterns of cold signals. Thermal afferent signals are modulated by hypothalamic temperature and subsequently cold sensation is modulated.
Peroneal nerve palsy developed in a patient with T cell-type acute lymphoblastic leukemia (ALL) is reported. In the fifth month after starting of chemotherapy against ALL, the patient, a 7-year-old girl, developed drop foot on the left. Three possibilities were considered as its pathogenesis; (1) VCR neuropathy, (2) neurotoxicity of intrathecal MTX, (3) leukemic invasion to the spinal canal. However, there was no evidence of leukemic invasion in any lumbar taps, and no improvement was obtained by cessation of VCR and intrathecal MTX. Examination by CT scan revealed tumors in the intervertebral (L5-S2) region, which was diagnosed to be neurofibromas by biopsy. The tumors compressed the left peroneal nerve and neurotoxicity of antineoplastic agents for ALL could be the cause of her drop foot.
A male with myelodysplastic syndrome (MDS) following aplastic anemia is reported. The patient had been diagnosed as aplastic anemia at 8 years of age, and treated with blood transfusions, anabolic and glucocorticoid steroid hormones. Over a period of subsequent twelve years, he had remission and deterioration. At the age of 21, the patient developed a sudden progression of severe anemia, when his bone marrow showed hyperplasia with prominent dyshematopoiesis and excess of blasts, compatible with MDS by the definition of FAB classification. He received low dose Ara-C therapy, which was ineffective. Nine months later he developed acute monocytic leukemia (M5b) and died. Chromosomal analysis revealed 46, XY at the onset of aplastic anemia, 46, XY, del (6) (q21 q27) at the MDS and 46, XY, -7, +21, 6q-/47, XY, +Y, -7, +21, 6q- at the acute leukemic stage.
A series of 305 infants and children between 1 day to 14 years of age were operated upon using caudal anesthesia. We used 1% mepivacaine 1.2 ml.kg-1 to obtain a level of anesthesia above T10, 1.0 ml.kg-1 above L1, and 0.8 ml.kg-1 above S. Complete failure occurred in 4.3% of patients. We investigated the blood concentration of mepivacaine in 17 patients, and it ranged from 0.5 microgram.ml-1 to 5.0 micrograms.ml-1. In a two month old infant, weighing 6.7 kg, apnea and bradycardia occurred. This was managed by tracheal intubation and controlled ventilation. But there were no other severe complications. We also investigated the distance between C7 and sacral hiatus (D) in each case. The coefficients of correlation between D and height is 0.97, and high correlation existed also between D and body weight (r = 0.93). This confirms that body weight can be used as a parameter to determine the dose of local anesthetic agent. We conclude that this technique is a safe, reliable and simple way to produce surgical analgesia in infants and children.
The clinical benefits of retrograde coronary sinus perfusion of a cardioplegic solution were investigated in 7 neonates and 23 infants undergoing Jatene operation. After an initial infusion of albumin-containing crystalloid cardioplegic solution via the aortic root, 21 patients received additional solution delivered by retrograde coronary sinus perfusion (retrograde group) and 9 patients received by selective antegrade coronary perfusion (antegrade group) every 20 to 30 minutes. There were no differences in age, weight, and left ventricular preoperative pressure and morphology between the two groups. Aortic cross-clamping time was 130 +/- 18 minutes in retrograde group and 147 +/- 20 minutes in antegrade group. Postoperative assays of CPK-MB, GOT and LDH, and hemodynamic measurements immediately after cessation of cardiopulmonary bypass (CPB) were carried out in all patients. Although there was no significant difference between the two groups in terms of enzyme indexes, retrograde group showed a greater variation of sigma CPK-MB from patient to patient than antegrade group. However, hemodynamic parameters of CVP, left atrial pressure and rate-pressure product at 20-30 minutes after CPB were similar in the two groups. Six neonates in retrograde group also demonstrated the similar enzyme indexes and hemodynamic state immediately after CPB to other older patients. We concluded, therefore, that retroperfusion of cardioplegic solution in neonates and infants provides satisfactory myocardial protection as well as antegrade perfusion, and it was a useful means of cardioplegic delivery in Jatene operation, because of its simplicity.
We investigated the effect of microinjection of endogenous pyrogen or interleukin-1 (EP/IL-1) into 40 selected brain regions on the circulating leukocyte count in rabbits. The results show that injections into the rostral region of the hypothalamus, especially the preoptic and anterior hypothalamus, induce leukocytosis.
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