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Biomedical subjects

J Sugawara

Publications and source records attributed to J Sugawara.

At least 37 records · Page 2Linked to original sources

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↗

Increased secretion of hepatocyte growth factor by eutopic endometrial stromal cells in women with endometriosis.

OBJECTIVE: We evaluated the secretion of hepatocyte growth factor by eutopic endometrial stromal cells in vitro. DESIGN: Eutopic endometrial stromal cells were isolated and the culture supernatants were collected after 48 hours of incubation. The secretion of hepatocyte growth factor was analyzed by ELISA. SETTING: Department of Obstetrics and Gynecology of Tohoku University Hospital. PATIENT(S): Specimens of endometrium in the proliferative phase were excised from 11 patients who were undergoing laparoscopy for infertility. Six of the patients had endometriosis and five did not. None of the patients had received hormonal treatment before surgery. RESULT(S): Hepatocyte growth factor secretion was found to be increased significantly in cultured endometrial stromal cells from the infertile patients with endometriosis compared with those without endometriosis. CONCLUSION(S): The secretion of hepatocyte growth factor was up-regulated in eutopic endometrial stromal cells from patients with endometriosis. An increase in hepatocyte growth factor production may be characteristic of endometriosis and may be involved in the pathophysiology of this disease.

Adult↗

Facial growth of skeletal Class III malocclusion and the effects, limitations, and long-term dentofacial adaptations to chincap therapy.

This article outlines the authors' research findings on the craniofacial growth of untreated skeletal Class III malocclusion, as well as the short-term and long-term effects of chincap orthopedic force for controlling Class III mandibular growth. Skeletal Class III malocclusion is believed to be the result of excessive growth of the mandible with respect to the maxilla and/or cranial base. The results of the authors' longitudinal studies show similar maxillary and mandibular incremental growth change during prepubertal, pubertal, and postpubertal periods when compared with Class I subjects. Therefore, it seems reasonable to assume that the skeletal framework of the Class III malocclusion must have been established before the prepubertal growth period. As for treatment with chincap appliances, the study on short-term and long-term effects indicate that, on average, the skeletal profile is greatly improved during the initial stages of chincap therapy. However, such changes are rarely maintained during pubertal growth period. Treatment with chincap appliances seldom alters the inherited prognathic characteristics of skeletal Class III profiles after completion of growth.

Adaptation, Physiological↗

Hepatocyte growth factor stimulated proliferation, migration, and lumen formation of human endometrial epithelial cells in vitro.

Human endometrial regeneration has been considered to be modulated by several growth factors. However, little is known about the detailed mechanisms involved in the repair of the endometrium during the menstrual period. Hepatocyte growth factor (HGF) is a pleiotropic growth factor that reportedly acts on various epithelial cells. In the present study, we observed HGF and mRNA expression in human endometrium and mRNA expression in cultured endometrial epithelial cells of the c-met gene by reverse transcription-polymerase chain reaction and Southern blot hybridization. We also examined the biological role of HGF on the regeneration of the endometrium by using cultured endometrial epithelial cells in their proliferative phase. With the proliferation assay, the addition of 10-50 ng/ml of HGF showed that HGF was mitogenic in a dose-dependent manner. With Boyden's chamber technique, 50 ng/ml of HGF significantly stimulated cell migration. In a three-dimensional cell-culture system, the endometrial epithelial cells formed cell clusters and gradually formed epithelial lumens, both of which were stimulated by 50 ng/ml of HGF. Results suggest the HGF stimulates the proliferation and migration of, and morphogenic changes in, endometrial epithelial cells. HGF may modulate the regeneration of the endometrium during menstruation.

Adult↗

Does apoptosis contribute follicular atresia and luteal regression in human ovary?

We investigated apoptosis in 37 human ovaries from normally cycling women to determine the mechanism of the various stages of follicular atresia and the regression of corpus luteum in human. Apoptosis was examined by 3'-hydroxy nick end-labeling, by immunostaining of an apoptosis-related antigen, Le(y) and by cell death-related genes, bcl-2. Immunoreactivity for Le(y) and nick end-labeling reactive cells were not observed in the follicular and luteal phases, except for scattered cells in the degenerating corpus luteum. On the other hand, immunoreactivity for bcl-2 was observed in the granulosa cells of antral follicles. These results indicated that apoptosis is not obvious through follicular maturation and luteal regression. This may be due to the relatively long process of human follicular growth and atresia.

Adult↗

A pressure-distribution sensor (PDS) for evaluation of lip functions.

The purpose of this study was to develop and to test a pressure-distribution sensor (PDS) for evaluating lip functions. The PDS is fabricated as a disposable cartridge and is based on the principle of optical-pressure conversion used in tactile sensors of robot arms. Its advantages are in measuring sealing forces, contact area, and pressure-distribution patterns of the lips at maximum effort. We used the PDS to evaluate pressure-distribution patterns of long-face subjects with extremely large interlabial distances. The results suggest that the PDS is a useful device for evaluating lip sealing functions and their changes after orthodontic therapy or orthognathic surgery.

Disposable Equipment↗

Surgical-orthodontic treatment in Class II, division 2, malocclusion: a case report involving pretreatment and posttreatment evaluation of temporomandibular dysfunction.

The case of a patient who had a significant Class II, division 2, malocclusion and experienced myofascial pain dysfunction is presented. The patient was a 22-year-old Japanese woman who complained of pain and fatigue in her masticatory muscles. During presurgical orthodontic treatment, a one-tooth osteotomy was utilized to correct the lingual inclination of an ankylosed maxillary central incisor. The surgery consisted of intrusion of the anterior segment of the maxilla, intrusion of the anterior segment of the mandible, mandibular advancement by sagittal split ramus osteotomy, and trimming of the gonial angles. Postoperatively, her facial appearance and occlusion were good. Furthermore, the function of the temporomandibular joints was improved and the symptoms of myofascial pain and dysfunction disappeared.

Adult↗

The role of macrophage colony stimulating factor in the peritoneal fluid in infertile patients with endometriosis.

Macrophage colony stimulating factor (M-CSF) concentrations in the peritoneal fluid of 44 infertile patients were measured. The concentration of M-CSF was significantly higher in the patients with endometriosis than in those without endometriosis. There was no significant difference between the M-CSF concentration and stage of endometriosis classified by revised American Fertility Society (rAFS) classification in the 44 patients. However, in primary infertility patients with endometriosis there was a significant correlation between peritoneal M-CSF levels and rAFS points of endometriosis. We speculate that there is some relationship between the increased levels of M-CSF in the peritoneal cavity and the primary infertility associated with endometriosis especially progression of endometriosis.

Ascitic Fluid↗

Growth of mandibular prognathism after pubertal growth peak.

This study deals with the growth changes of the Japanese face associated with mandibular prognathism during 3 years after the pubertal growth peak. The investigation was based on the serial lateral cephalometric roentgenograms of prognathic and normal males and females, respectively. Maturational stages of the pubertal growth were determined individually by the ossification events taken from hand-wrist radiographs. Results indicate that the morphologic characteristics of the mandibular prognathism, which are established before the pubertal growth peak, are strongly maintained during the period studied. However, mandibular prognathism seems to show a manner of growth change fairly similar to that of the normal after the pubertal growth peak.

Adolescent↗

Age-related decline of cerebral oxygen metabolism in normal population detected with positron emission tomography.

Using positron emission tomography (PET), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured in 32 healthy volunteers aged from 27 to 67 years. In bilateral putamen, left supratemporal, left infrafrontal and left parietal cortices, CMRO2 showed a significant decline during aging. The age-related decline of CBF was seen only at the left superior temporal cortex. The mean CMRO2 was significantly lower in the elder group (over 51 years old) than in the younger group (under 50 years old), whereas no significant difference in mean CBF between the two groups. The poor correlation of CBF to the age could be explained partly by the fact that CBF is easily influenced by the physiological, psychological and/or environmental factors. The age-related changes of CMRO2 were more marked in the association cortices of the left hemisphere than in that of the right hemisphere.

Adult↗

Long-term effects of chincap therapy on skeletal profile in mandibular prognathism.

The purpose of this study was to investigate the long-term changes in the skeletal Class III profile subsequent to chincap therapy. The sample consisted of 63 Japanese girls who had skeletal Class III malocclusions before treatment. All underwent chincap therapy from the beginning of treatment. The duration of chincap therapy varied but averaged 4 1/2 years. The samples were divided into the following three groups according to their ages when chincap therapy was started: A group that started at 7 years of age (n = 23), a group that started at 9 years of age (n = 20), and one that started at 11 years of age (n = 20). The data were derived from lateral cephalometric head films, taken serially at the ages of 7, 9, 11, 14, and 17 years. Skeletal facial diagrams were constructed by X-Y coordinates of representative cephalometric landmarks. The data were analyzed statistically. The results of the present study were as follows: (1) The mandible showed no forward growth during the initial stages of chincap treatment in all three groups. (2) Patients who had entered treatment at 7 and 9 years of age appeared to show a catch-up manner of mandibular displacement in a forward and downward direction before growth was completed. (3) There was no statistical difference in the final skeletal profile between the group that had entered treatment at age 7 and the one that had entered at age 11. In conclusion, the skeletal profile was greatly improved during the initial stages of chincap therapy, but such changes were often not maintained thereafter. This finding indicated that chincap therapy did not necessarily guarantee positive correction of skeletal profile after complete growth.

Cephalometry↗