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Biomedical subjects

J Sugawara

Publications and source records attributed to J Sugawara.

At least 19 recordsLinked to original sources

Effects of exercise training of 8 weeks and detraining on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans.

Vascular endothelial cells produce nitric oxide (NO), which is a potent vasodilator substance and has been proposed as having antiatherosclerotic property. Vascular endothelial cells also produce endothelin-1 (ET-1), which is a potent vasoconstrictor peptide and has potent proliferating activity on vascular smooth muscle cells. Therefore, ET-1 has been implicated in the progression of atheromatous vascular disease. Because exercise training has been reported to produce an alteration in the function of vascular endothelial cells in animals, we hypothesized that exercise training influences the production of NO and ET-1 in humans. The purpose of the present study was to examine whether chronic exercise could influence the plasma levels of NO (measured as the stable end product of NO, i.e., nitrite/nitrate [NOx]) and ET-1 in humans. Eight healthy young subjects (20.3 +/- 0.5 yr old) participated in the study and exercised by cycling on a leg ergometer (70% VO2max for 1 hour, 3-4 days/week) for 8 weeks. Venous plasma concentrations of NOx and ET-1 were measured before and after (immediately before the end of 8-week exercise training) the exercise training, and also after the 4th and 8th week after the cessation of training. The VO2max significantly increased after exercise training. After the exercise training, the plasma concentration of NOx significantly increased (30.69 +/- 3.20 vs. 48.64 +/- 8.16 micromol/L, p < 0.05), and the plasma concentration of ET-1 significantly decreased (1.65 +/- 0.14 vs. 1.23 +/- 0.12 pg/mL, p < 0.05). The increase in NOx level and the decrease in ET-1 level lasted to the 4th week after the cessation of exercise training and these levels (levels of NOx and ET-1) returned to the basal levels (the levels before the exercise training) in the 8th week after the cessation of exercise training. There was a significant negative correlation between plasma NOx concentration and plasma ET-1 concentration. The present study suggests that chronic exercise causes an increase in production of NO and a decrease in production of ET-1 in humans, which may produce beneficial effects (i.e., vasodilative and antiatherosclerotic) on the cardiovascular system.

Adult↗

Change in post-exercise vagal reactivation with exercise training and detraining in young men.

We studied the effects of aerobic exercise training and detraining in humans on post-exercise vagal reactivation. Ten healthy untrained men trained for 8 weeks using a cycle ergometer [70% of initial maximal oxygen uptake (VO2max) for 1 h, 3-4 days.week-1] and then did not exercise for the next 4 weeks. Post-exercise vagal reactivation was evaluated as the time constant of the beat-by-beat decrease in heart rate during the 30 s (t30) immediately following 4 min exercise at 80% of ventilatory threshold (VT). The VO2max and the oxygen uptake at VT had significantly increased after the 8 weeks training programme (P < 0.0001, P < 0.001, respectively). The t30 had shortened after training, and values after 4 weeks and 8 weeks of training were significantly shorter than the initial t30 (P < 0.05, P < 0.01, respectively). The change in the t30 after 8 weeks of training closely and inversely correlated with the initial t30 (r = -0.965, P < 0.0001). The reduced t30 was prolonged significantly after 2 weeks of detraining, and had returned almost to the baseline level after a further 2 weeks of detraining. These results suggest that aerobic exercise training of moderate intensity accelerates post-exercise vagal reactivation, but that the accelerated function regresses within a few weeks of detraining.

Adult↗

Hypersomnia due to acute disseminated encephalomyelitis in a 5-year-old girl.

A 5-year-old girl suffering from hypersomnia due to acute disseminated encephalomyelitis (ADEM) is reported. Brain CT revealed a large low-density lesion involving the lentiform nucleus, posterior limb of the internal capsule, thalamus, posterior hypothalamus and midbrain in the left side. She was treated with intravenous dexamethazone. After the initial dose of dexamethazone, hypersomnia was dramatically and rapidly improved. A later brain CT study disclosed that the lesion in the brain disappeared. The brain lesion in this case involved the waking center in the brain, which was described by Von Economo. We concluded that hypersomnia in this case was due to ADEM involving the neural mechanism for maintaing wakefulness, probably in the thalamus and posterior hypothalamus. Repeat all night polysomnograpy in this case disclosed prolonged total sleep time and increased amount of stage 3-4 sleep in the hypersomniac state.

Journal Article↗

The influences of molar intrusion on the inferior alveolar neurovascular bundle and root using the skeletal anchorage system in dogs.

The skeletal anchorage system (SAS) was developed as intraoral rigid anchors for open-bite correction by intrusion of molars. Since the application of SAS is a new modality in orthodontic treatment, the influences of radical molar intrusion on the root and the inferior alveolar neurovascular bundle were unknown. The purpose of this research is to verify the effect of molar intrusion on the neurovascular bundle, the level of osseointegration of bone screws, and root resorption. The results of this study showed mandibular molars were intruded 3.4 mm on the average over 7 months in dogs. The miniplates were well stabilized with osseointegrated bone screws and the peri-implant soft tissues showed slight inflammatory changes. Neither nerves nor blood vessels were damaged. Root resorption was observed but was repaired with new cementum. We concluded that the SAS utilizing transmucosal titanium miniplates as an immovable orthodontic anchorage could provide a new modality for molar intrusions without serious iatrogenic problems.

Alveolar Process↗

Lithium affects the reactivities of GalNAcalpha1-3GalNAc-lipid and fibrinopeptide A in mice.

The relationship between lithium and the reactivities of GalNAcalpha1-3GalNAc-lipid and fibrinopeptide A were investigated in mice. Lithium strongly decreased glycolipid reactivity and slightly increased peptide reactivity in a dose- and time-dependent manner. These substances showed antidepressive behavioral effects in mice via different neurological activities. This many suggest a mechanism of two different clinical effects of lithium: one of which is a strong antimanic effect and one of which is a weak antidepressive effect.

Animals↗

Diurnal variations of post-exercise parasympathetic nervous reactivation in different chronotypes.

The purpose of this study was to investigate the diurnal variation and chronotype differences, i.e., in morning-types and evening-types, in post-exercise vagal reactivation. Twelve healthy male college students who were classified as morning-type (6) and evening-type (6), based on responses to a questionnaire, participated in this study. Postexercise vagal reactivation was assessed as the time constant of the beat-by-beat heart rate decrease for the first 30 sec after exercise (T30) at an intensity lower than the ventilatory threshold. The subjects performed 3-min cycle ergometer exercise at an intensity corresponding to 80% of the ventilatory threshold after a 1 min warm-up exercise in the morning (7:00 - 8:00) and evening (17:00 - 18:00) to obtain the T30. A significant interaction (chronotype-by-time) effect was found for T30. The morning value of the T30 in evening-type subjects was significantly larger than their evening value and the morning value in morning-type subjects. There was no significant interaction effect for heart rate and oxygen uptake during exercise. These results suggest that diurnal variation in post-exercise vagal reactivation is different between morning-type and evening-type, and post-exercise vagal reactivation in evening-type individuals is sluggish in the morning.

Adult↗

The current status of gynecological laparoscopic surgery in educational facilities in Japan.

A questionnaire survey was administered by Tohoku University hospital to investigate the current status of gynecological laparoscopic operations in teaching hospitals in which residents were trained as obstetricians and gynecologists. Thirty-eight senior doctors in 18 hospitals were sent a postal questionnaire. The response rates of facilities and doctors were 94.4% and 76.3% respectively. Diagnostic and operative laparoscopy was performed in all of the hospitals surveyed, however only a few hospitals performed more than 100 laparoscopies per year, and many surgeons did not perform advanced laparoscopic operations including hysterectomy, myomectomy and lymphadenectomy. Half of the doctors performed minilaparotomy, which is a so-called "open" technique. The standard surgical style involved the use of a carbon dioxide (CO2) pneumoperitoneum and an endoscope 10 mm in diameter. Unipolar endocoagulating instruments were generally used for hemostasis and incision. Most of the doctors surveyed thought that operative laparoscopy would become a necessary procedure in gynecological field, and half of them hoped to receive training in the technique. Instruction of expert endoscopic surgeons is necessary, especially in teaching hospitals, for the spread of safe and advanced laparoscopic surgery. An educational and training system for established surgeons as well as for young residents is urgently needed in Japan.

Delivery, Obstetric↗

Glycoside in schizophrenic patients sera affects behavior of mouse forced swimming.

We found a glycoside in sera of schizophrenic patients. This glycoside increased climbing of mouse forced swimming and the climbing was decreased by dopamine D1 receptor antagonist SCH-23390 with a dose dependent manner. This glycoside had much reactivity of GalNAc alpha1-3GalNAc, but not that of polymannoses nor that of Gal beta1-3GlcNAc alpha1-serine or threonine. This strongly suggests that the glycoside is an isolated O-glycoside, but not N-glycoside nor O-glycoside having core 1 or 2. The present findings suggest that schizophrenic patients have the special glycoside affecting the D1 receptor activity in their serum.

Adult↗

Regulation of insulin-like growth factor-binding protein 1 by hypoxia and 3',5'-cyclic adenosine monophosphate is additive in HepG2 cells.

Insulin-like growth factor-binding protein 1 (IGFBP-1) is important in regulating minute-to-minute IGF bioavailability in the circulation and is primarily an inhibitor of IGF action systemically and in most cellular systems. Understanding regulation of IGFBP-1 is, thus, important in understanding regulation of IGF actions. The IGFBP-1 promoter contains a cAMP response element, and cAMP stimulates IGFBP-1 gene expression at the transcriptional level. Recently, we have found three consensus sequences for the hypoxia response element in intron 1 of the IGFBP-1 gene. Herein, we have investigated the effects of hypoxia and a cAMP analog, 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP), on IGFBP-1 expression in HepG2 cells, a model system for IGFBP-1 gene regulation. HepG2 cells were exposed to normoxia (20% pO2) or hypoxia (2% pO2) for 24 h in the absence or presence of 8-Br-cAMP (0.1, 0.5, and 1 mM). Western ligand blotting revealed IGFBP-1 as the predominant IGFBP in HepG2-conditioned media, which increased in a dose-dependent manner after incubation with 8-Br-cAMP in normoxia and hypoxia (3-fold and 7-fold at 1 mM, respectively). Under hypoxic, compared with normoxic, conditions, IGFBP-1 protein and messenger RNA (mRNA) levels increased approximately 10-fold and 20-fold, respectively. In normoxia, 8-Br-cAMP stimulated IGFBP-1 protein and mRNA levels in a dose-dependent manner (7-fold and 10-fold at 1 mM). Hypoxia and 8-Br-cAMP showed additive stimulatory effects on IGFBP-1 protein and mRNA levels (35-fold and 50-fold at 1 mM) that were time and dose dependent. Primary transcripts of IGFBP-1 mRNA were increased concordantly with IGFBP-1 mRNA. The half-life of the IGFBP-1 mRNA was markedly increased (approximately 6-fold) by hypoxia, and cAMP minimally enhanced this effect. These results demonstrate that hypoxia and compounds that increase intracellular cAMP additively regulate IGFBP-1 gene expression by transcriptional and posttranscriptional mechanisms. Regulation of IGFBP-1 mRNA and protein by cAMP and hypoxia may be important for understanding the physiologic and pathophysiologic roles of IGFBP-1.

8-Bromo Cyclic Adenosine Monophosphate↗

Regulation of insulin-like growth factor-binding protein-1 by nitric oxide under hypoxic conditions.

Nitric oxide (NO) is believed to play an important, but as yet undefined, role in regulating hypoxia inducible gene expression. Recently, we have reported evidence suggesting that the human insulin-like growth factor-binding protein-1 (IGFBP-1) gene is directly regulated by hypoxia through the hypoxia-inducible factor-1 pathway. The goal of the current study was to investigate NO regulation of hypoxic induction of IGFBP-1 gene expression using HepG2 cells, a model system of hepatic gene expression. We report that a NO generator, sodium nitroprusside, significantly diminishes hypoxic activation of IGFBP-1 protein and messenger ribonucleic acid expression. Furthermore, these effects are independent of guanylate cyclase/ cGMP signaling, as two different inhibitors, LY 83583, a specific inhibitor of guanylate cyclase, and KT 5823, a protein kinase G inhibitor, had no effect on IGFBP-1 induction by hypoxia. Hypoxic induction of a reporter gene containing four tandemly ligated hypoxia response elements was completely blocked by sodium nitroprusside, but not by 8-bromo-cGMP, an analog ofcGMP. These results suggest that NO blocks hypoxic induction of IGFBP-1 by a guanylate cyclase/ cGMP-independent pathway, possibly at the level of oxygen sensing. The impaired hypoxia regulation of IGFBP-1 by nitric oxide may play a key role in the hyperinduction of IGFBP-1 observed in pathophysiological conditions such as fetal hypoxia and preeclampsia where dysregulation of NO has been observed.

Alkaloids↗

Long-term dentofacial stability after bimaxillary surgery in skeletal Class III open bite patients.

The purpose of this study was to evaluate long-term dentofacial stability after bimaxillary surgery in skeletal Class III open bite patients. Twenty-three Japanese adults (5 males, 18 females) were randomly selected as the experimental group from the files of Tohoku University Dental Hospital according to the following criteria: (1) skeletal Class III malocclusion with anterior open bite, (2) simultaneous Le Fort I and sagittal split ramus osteotomies, and (3) complete set of cephalograms taken at predetermined intervals until 5 years after debonding. Based on the manner of maxillary surgical repositioning, they were divided into the following 2 groups: (1) impaction group of 13 subjects (2 males, 11 females) who had maxillary superior repositioning without rotation of the palatal plane, and (2) rotation group of 10 subjects (3 males, 7 females) who had maxillary repositioning with clockwise rotation of the palatal plane. These patients were compared to a control group of 11 adults (1 male, 10 females) with skeletal Class III malocclusion without open bite who underwent bimaxillary surgery by the same techniques. Our data showed that overbite stability in the rotation group was better than that in the impaction group. This suggests that clockwise rotation of the palatal plane, which moves the anterior maxillary structures down, is an effective way to produce a reasonably stable correction of the anterior open bite. In contrast, superior repositioning of the maxilla that significantly rotates the mandible in the closing direction should be applied with caution.

Adolescent↗

Skeletal anchorage system for open-bite correction.

A skeletal anchorage system was developed for tooth movements. It consists of a titanium miniplate that is temporarily implanted in the maxilla or the mandible as an immobile anchorage. In this article, we introduce the skeletal anchorage system to intrude the lower molars in open-bite malocclusion and evaluate the results of treatment in two severe open-bite cases that underwent orthodontic treatment with the system. Titanium miniplates were fixed at the buccal cortical bone around the apical regions of the lower first and second molars on both the right and left sides. Elastic threads were used as a source of orthodontic force to reduce excessive molar height. The lower molars were intruded about 3 to 5 mm, and open-bite was significantly improved with little if any extrusion of the lower incisors. No serious side-effects were observed during the orthodontic treatment. The system was also very effective for controlling the cant and level of the occlusal plane during orthodontic open-bite correction.

Adolescent↗

Intercellular adhesion molecule-1 and hepatocyte growth factor in human endometriosis: original investigation and a review of literature.

Defects in the cell-mediated immune system may play a role in the pathogenesis or progression of pelvic endometriosis. Possible mediators include macrophages, interleukins-1 and -6, and tumor necrosis factor-alpha. More recent work points to the involvement of adhesion molecules and growth factors. To clarify the pathogenesis of endometriosis, we compared the characteristics of soluble intercellular adhesion molecule-1 (soluble ICAM-1) and hepatocyte growth factor (HGF) in women with and without endometriosis. We found that, in patients with endometriosis, the concentrations of soluble ICAM-1 in peritoneal fluid increased and interfered with the activity of natural killer cells. We also found that HGF secretion was significantly increased in cultured endometrial stromal cells, and that HGF stimulated the proliferation and migration of, and morphogenic changes in, endometrial epithelial cells. HGF and ICAM-1 play important roles in the initiation and regulation of endometriotic lesions on the microenvironment level. The increased secretion of HGF by eutopic endometrial stromal cells may contribute to the pathogenesis of endometriosis, whereas the increased levels of soluble ICAM-1 may impair natural killer cell activity and accelerate the progression of the disease.

Cell Division↗

Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: a possible model for IGFBP-1 expression in fetal hypoxia.

IGFBP-1 is elevated in fetuses with long-term, chronic hypoxia and intrauterine growth restriction. We investigated the hypothesis that hypoxia regulates IGFBP-1 in the human fetus in vivo and IGFBP-1 gene expression and protein in vitro. Umbilical artery IGFBP-1 levels (mean +/- SEM) from term babies with respiratory acidosis (acute hypoxia), normal babies, and those with mixed respiratory/metabolic acidosis (more profound and prolonged hypoxia) were measured using an immunoradiometric assay. IGFBP-1 levels were similar in normal (n = 12) and acutely hypoxic (n = 6) babies (189.1 +/- 71.8 vs. 175.8 +/- 45.9 ng /ml, respectively, P = 0.789). However, with more profound and prolonged hypoxia (n = 19), IGFBP-1 levels were markedly elevated (470.6 +/- 80.0 ng /ml, P = 0.044). To investigate IGFBP-1 regulation by hypoxia in vitro, HepG2 cells were incubated under hypoxia (pO2 = 2%) and normoxia (pO2 = 20%). IGFBP-1 protein and mRNA increased 8- and 12-fold, respectively, under hypoxic conditions. Hypoxia did not affect protein or mRNA levels of IGFBP-2 or -4. IGFBP-5 and -6 mRNAs, undetectable in control cells, were not induced by hypoxia, whereas minimally expressed IGFBP-3 mRNA increased twofold. Investigation into IGFBP-1 gene structure revealed three potential consensus sequences for the hypoxia response element (HRE) in the first intron. To investigate functionality, a 372-bp fragment of IGFBP-1 intron 1, containing putative HREs, was placed 5' to a heterologous hsp70 promoter in a plasmid using luciferase as a reporter gene. Under hypoxia, reporter gene activity increased up to 30-fold. Mutations in the middle HRE abolished reporter activity in response to hypoxia, suggesting that this HRE is functional in the IGFBP-1 hypoxia response. Cotransfection of HRE reporter genes with a constitutively expressing hypoxia-inducible factor 1 plasmid in HepG2 cells resulted in a fourfold induction of reporter activity, suggesting a role for hypoxia-inducible factor 1 in hypoxia induction of IGFBP-1 gene expression. These data support the hypothesis that hypoxia regulation of IGFBP-1 may be a mechanism operating in the human fetus to restrict insulin-like growth factor-mediated growth in utero under conditions of chronic hypoxia and limited substrate availability.

Animals↗

Subcellular localization of myosin I in A10 smooth muscle cell.

We isolated and identified a 110-kDa myosin I from porcine aorta media smooth muscle [Y. Hasegawa et al. (1996) J. Biochem. 120, 971-976]. Partial peptide sequences of the 110-kDa myosin I fragments were homologous to amino acid sequences deduced from myosin Ibeta of bovine brain and adrenal gland. We investigated biochemically the distribution of the 110-kDa myosin I by cell fractionation methods. About 10% of myosin I present in whole cells could be extracted by treatment with 0.02% saponin, which does not liberate organelles, indicating that at least 10% of myosin I present in A10 cells is associated with neither organelles nor cytoskeleton. After treatment of A10 cells with 0.5% Triton X-100, the insoluble cytoskeleton contained 45% of myosin I present in whole cells. Treatment with MgATP extracted most of myosin I from the cytoskeleton, indicating that the distribution of myosin I is maintained by binding of the myosin I head to an actin filament. On the other hand, when the cell homogenate was fractionated on sucrose density step gradients, about 80% of myosin I was associated with membranes of various densities. An attempt to dissociate the myosin I from the membranes in the presence of MgATP was not successful. These results show that about 80% of total myosin I is associated directly with membranes, not through F-actin. The amounts of myosin I associated with membranes or cytoskeleton provide evidence that myosin I in A10 cells is associated in part with only membrane and in part with both cytoskeleton and membranes. Our results lead to conclusion that myosin I exist in several states: membrane-and-cytoskeleton-associated, membrane-associated, and membrane-and-cytoskeleton-free. These states may be in dynamic equilibrium, allowing myosin I to respond to the cellular requirements.

Amino Acid Sequence↗

Effects of granisetron, a selective 5-HT3 receptor antagonist, on ouabain-induced emesis in ferrets.

The antiemetic effect of granisetron, a selective 5-HT3 receptor antagonist, on ouabain-induced emesis was studied using ferrets. In order to clarify the relationship between ouabain-induced emesis and serotonin (5-HT), we examined its effects on 5-HT release from the isolated ileum. Afferent vagal nerve activity was also determined. An intravenous bolus injection of ouabain (0.1-1.0 mg/kg) produced emesis in a dose-dependent manner. Ouabain-induced emesis was inhibited by pretreatment with granisetron. In the isolated ileum, ouabain induced a concentration-dependent increase of 5-HT. This release of 5-HT was suppressed by granisetron. Increases in vagal nerve discharges were observed immediately after the intravenous administration of ouabain (0.1-1.0 mg/kg). These increases were suppressed by granisetron. Taken together, ouabain activates 5-HT release from the mucosa in the gastrointestinal tract. Released 5-HT may activate the vagal afferent nerves, resulting in vomiting. Granisetron inhibited the ouabain-induced elevation of 5-HT and vagal nerve activity. Ouabain may induce emesis as well as negative chronotropic effects by activating the vagus. Our results suggest that ouabain-induced emesis is in part mediated by the 5-HT3 receptors of the peripheral gastrointestinal tract.

Abdomen↗

Use of selectively colored stereolithography for diagnosis of impacted supernumerary teeth for a patient with cleidocranial dysplasia.

The objective of the present study was to develop a three-dimensional method of locating the position of impacted supernumerary teeth in a patient with cleidocranial dysplasia. Stereolithographies of the patient's teeth and maxillofacial structure were prepared, coloring the teeth red. This model established accurate tooth malposition and provided support for selection of surgical exposure for extraction and traction of the impacted teeth. Selectively colored stereolithography is expected to be useful in a number of diverse situations.

Adolescent↗