Effects of immunosuppressant agents on growth hormone release and gene expression.
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Animals↗
Biomedical subjects
T Ohyama
Publications and source records attributed to T Ohyama.
Expression of cell adhesion molecule CD44 and sialyl Lewis A in gastric carcinoma and colorectal carcinoma in association with hepatic metastasis.
To clarify the role of the expression of adhesive molecules [CD44 (standard form) and sialyl Lewis A (sialyl Lea)] on hepatic metastasis, 108 advanced gastric carcinomas and 94 advanced colorectal carcinomas were investigated immunohistochemically. Multivariate analysis demonstrated that CD44 expression and lymph node metastasis in gastric cancer and CD44 and sialyl Lea expression in colorectal cancer were significantly related to hepatic metastasis. The incidence of hepatic metastasis was highest in patients with the expression of both CD44 and sialyl Lea. The expression of CD44 standard form as well as sialyl Lea may have a major role as adhesion molecules in the process of hepatic metastasis.
Carcinoma↗
Mobility of the obturator prosthesis in hemimaxillectomy edentulous patients.
In edentulous patients with maxillary defects, it is difficult to obtain sufficient retention, support, and stability of the obturator prosthesis, in addition, its mobility during various functions is considered to be large. A thorough understanding of the mobility of the obturator prosthesis is important to achieve successful results in the patient's oral rehabilitation. In this study, the ranges of movement of the obturator prostheses in three hemimaxillectomy edentulous patients were compared during tapping, chewing (biscuit), and opening and clenching jaw movements by simultaneously conducting three-dimensional measurements of three points that were established on the central incisor and the right and left first molars of the obturator prosthesis with a jaw movement tracking device having six degrees of freedom. This study indicates that the range of movement of the obturator prosthesis varied extensively from individual to individual. The ranges of movement were larger than those of normal complete dentures and differed considerably from each other when categorized according to the three functions and three measuring points in the patients.
Aged↗
Effect of teeth clenching on isometric and isokinetic strength of ankle plantar flexion.
To investigate the effect of voluntary teeth clenching on the isometric and isokinetic exercises of the lower limbs, the association of muscle strength (peak torque, PT) and muscle activities (integrated electromyographic activity per unit of time, iEMG/s) of the three muscles of the triceps surae with teeth clenching during isometric and isokinetic plantar flexion were simultaneously measured for 12 healthy male volunteers using a Cybex 6000 Extremity Testing and Rehabilitation System and a surface EMG analyzing system. The statistical analysis demonstrated that for the isometric exercise, PT and each iEMG/s significantly increased in association with teeth clenching, and a positive correlation existed between the biting force and each variable. In contrast, no association was found with teeth clenching for the isokinetic exercise. In this study, therefore, it was found that the effect of teeth clenching differed between the isometric and isokinetic exercises.
Adult↗
Application of modal analysis to human subjects: comparison of healthy subjects and cleft lip and palate subjects.
To evaluate the vibrational characteristics of the maxillary arch, modal analysis was applied to human subjects. Twelve healthy human subjects and 2 cleft lip and palate (CLP) subjects with surgical failure in their cleft area were chosen for this study. The main measurement system was composed of an impact hammer, acceleration sensor, CF-6400 FFT Analyzer, PC-9821Xn personal computer, and Vibrant PC modal analysis software. The measurement points were established on 12 teeth between the upper first molars on both sides of the mouth in healthy subjects, and on 10 teeth in CLP subjects. In all subjects, one distinct resonance peak was observed in each transfer function at each measurement point. All of the transfer functions of a given subject strongly resembled each other in terms of shape. The amplitude and modal shapes of the maxillary arches of all the subjects were obtained by using a curve-fitting function in the software. In the healthy subjects, the maxillary arch expanded outward and shrank inward on vibration with no node after an impact. In the CLP subjects, the phase lag between the large and small segment was distinctly observed after an impact. In this study, the applicability of modal analysis for human subjects was demonstrated.
Adult↗
Evaluation of athletic mouthguard through vibration test on maxillary teeth of human dry skull.
The athletic mouthguard has been used for the prevention of orofacial injuries in contact sports. In this research, the effectiveness of a mouthguard was evaluated for its protection of the maxillary teeth of a human dry skull through experimental modal analysis. The upper central incisor was excited by an electrodynamic shaker. The frequency response functions of the upper teeth were then recorded on an FFT analyzer in order to identify modal shapes of the maxillary arch with and without a mouthguard. In addition, transient response simulations were carried out and decay rates of transient response waves were compared. As a result, when the mouthguard was in place, the resonance peaks of the frequency response functions were dampened, and the nodes of the modal shapes for the anterior teeth were indefinite in the frequency domain over 1 kHz. In the transient response simulation, the decay rates of transient response waves when the mouthguard was used were significantly higher than those when the mouthguard was not used (p<0.01). The results suggest that the mouthguard relieves the stress concentrated on the anterior teeth in a frontal collision by absorbing and dispersing some of the shock energy, thus quickly stopping the vibration of the maxillary teeth. These findings support the clinical fact that mouthguards prevent orofacial injuries in sporting activities.
Athletic Injuries↗
Anti-thrombotic effects of CX-397, a recombinant hirudin analog, in a canine model of coronary artery thrombosis.
CX-397, a recombinant hirudin analog, is a potent and specific inhibitor of human alpha-thrombin. We conducted a comparative study of CX-397 and heparin in a canine model of left circumflex (LCX) coronary artery thrombosis to evaluate the anti-thrombotic efficacy of CX-397. Administration of drugs (i.v.; bolus + infusion) was commenced 10 min prior to the initiation of LCX coronary artery electrolytic injury (100 microA for 300 min). All saline-treated control animals (7/7) developed thrombotic occlusion during the experimental period, leaving a residual thrombus mass of 15.4 +/- 3.8 mg. Treatment with CX-397 at three incremental dose levels reduced the incidence of occlusion (4/7, 2/5 and 0/7) and decreased thrombus weight (12.6 +/- 2.5 mg, 6.3 +/- 3.0 mg and 2.1 +/- 1.3 mg, respectively) in a dose-dependent manner. At the intermediate dose (15,000 ATU/kg + 15,000 ATU/kg/h) or higher, CX-397 showed significant anti-thrombotic effects (p <0.05 and p <0.01) and suppressed increases in thrombin-antithrombin III complex (TAT) levels (p <0.01 and p <0.001). In the heparin (80 U/kg + 60 U/kg/h)-treated group, the incidence of occlusion (5/7) and thrombus weight (14.1 +/- 6.2 mg) did not differ significantly from the control group. Plasma TAT levels in the heparin group decreased compared with the control group (p <0.01), but was less potent than the intermediate dose CX-397 (p <0.01). The anti-coagulation (activated partial thromboplastin time and activated clotting time) and template bleeding time prolongation effects of heparin were more potent than those of the intermediate dose CX-397 which showed significant anti-thrombotic effects. In conclusion, CX-397 dose-dependently suppressed thrombus formation by inhibition of thrombin activity in a canine coronary artery injury model. The anti-thrombotic efficacy of CX-397 was more potent than that of heparin at equivalent anti-coagulation dosage.
Animals↗
[Mechanism of transcriptional regulation by bent DNA structures].
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Animals↗
Characterization of the pUC19-lacZC141 reversion system for assaying chemical mutagenesis.
pUC19-lacZC141 DNA contains a proline codon at positions 141 to 143, where an alanine codon normally appears in the original lacZ gene. pUC19-lacZC141 DNA was produced using site-directed mutagenesis. After transfection of pUC19-lacZC141 DNA into lacZ hosts, the transformants produce white colonies on an agar plate containing X-gal and IPTG. lacZ+ revertants can be identified by their dark- and light-blue colony color against a background of non-mutant white colonies, indicating restoration of beta-galactosidase activity. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) and methylmethanesulfonate (MMS) were used to characterize the pUC19-lacZC141 DNA reversion assay. Mutagenesis resulting from methylated DNA was examined in Escherichia coli strains JM109, BMH71-18mutS, and SURE, which differ in their repair systems for DNA damage. In JM109 and BMH71-18mutS, mostly G:C-->A:T transitions and some G:C-->C:G or G:C-->T:A transversions were observed. E. coli SURE produced, in addition, frameshift mutations (approximately 10%). The DNA sequence analysis of 174 induced mutants indicated that the major effect of methylation is on single base-pair substitutions with a slight effect on deletion frameshifts. All mutations are consistent with miscoding of guanine or cytosine adducts or lesions. Transitions account for 158 of 165 (96%) induced base substitutions. Approximately 93% of the base-substitution mutations occurred at the expected positions 141 to 143 in the lacZ gene. The pUC19-lacZC141 assay was sufficiently sensitive to allow the detection of mutations in lacZ- hosts with different repair mechanisms. The pUC19-lacZC141 DNA reversion system will permit the assaying of other chemicals not otherwise amenable to mutagenesis studies.
DNA Methylation↗
Metal-induced hydroxyl radical generation by Cu(+)-metallothioneins from LEC rat liver.
Reactions of LEC (Long-Evans rats with a cinnamonlike coat color) rat liver Cu(I)-metallothioneins (MTs) with HgCl2 or K3Fe(CN)6 were investigated by ESR spectroscopy and generation of hydroxyl radicals was demonstrated using the ESR spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO). When Cu(I)-MTs were incubated with more than one equivalent mole HgCl2 or K3Fe(CN)6 to Cu+ bound to MTs, strong signals due to Cu2+ appeared. ESR spectra, which were a combination of the DMPO-OH adduct signal and a six-line signal, were observed in the reaction of Cu(I)-MTs with HgCl2, whereas no oxygen radical signal was seen with K3Fe(CN)6. The DMPO-OH signal intensity was greater in the presence of SOD while the signal disappeared in the presence of catalase. The results suggest that addition of HgCl2 causes the liberation of cuprous ions from MTs followed by a reaction with oxygen, leading to hydroxyl radical formation through a Fenton-type Haber-Weiss reaction.
Animals↗
Distant lymph node metastasis of early gastric cancer.
Among 601 patients with early gastric cancer (EGC), the clinicopathological findings of 5 patients (invasion of the mucosal layer in 2 and of the submucosal layer in 3) with distant lymph node metastasis according to TNM classification (third- or fourth-tier lymph node metastasis according to the Japanese classification) were investigated. The proliferating-cell nuclear antigen (PCNA) expression of EGC was also examined immunohistologically. The sites of distant metastasis were the nodes at the root of the mesentery, in the hepatoduodenal ligament, and the paraaortic nodes. While the PCNA-positive rate of EGC with distant lymph node metastasis (35.4%) was significantly higher than that of EGC without lymph node metastasis (14.7% P = 0.01), it was similar to that of EGC with perigastric lymph node metastasis. The cumulative survival rate of the EGC patients with distant lymph node metastasis (5-year survival rate 20.0%) was significantly lower than that without lymph node metastasis (88.2%, P < 0.0001), first-tier lymph node metastasis (76.9%, P < 0.04), or second-tier lymph node metastasis (77.1%, P < 0.04). Thus, although the prognosis of EGC patients with distant lymph node metastasis was poor, a dissection of the distant lymph nodes should be performed when metastasis is suspected.
Adenocarcinoma↗
Overexpression of bax sensitizes breast cancer MCF-7 cells to cisplatin and etoposide.
Bax, one of the bcl-2 family genes, is expressed in a number of untransformed cell lines and various breast tissues, whereas only weak or no expression has been detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weak bax gene expression, were stably transfected with pCX2neo bax, encoding human bax; and two unique clones, MCF-7/bax-1 and MCF-7/ bax-2, that expressed different levels of bax were generated. Sensitivity to cisplatin (CDDP) and etoposide (VP-16) was examined and each stable transfectant was more sensitive to these agents than the parental MCF-7 cells. The degree of enhancement in sensitivity to these anticancer agents was dependent on the expression level of bax. The enzyme-linked immunosorbent assay (ELISA), which quantifies DNA damage, demonstrated that this sensitization was due to apoptosis. Thus, we suggest that exogenous bax-alpha overexpression may be one of the factors determining cellular chemosensitivity in MCF-7 breast cancer cells and that it could be applied therapeutically to enhance chemosensitivity in breast cancer cells.
Antineoplastic Agents↗
Effects of dopaminergic agents on reversal of reserpine-induced impairment in conditioned avoidance response in rats.
Male Slc:Wistar, Std:Wistar, and Slc:F344/N rats had good acquisition of the conditioned avoidance response (CAR), while that of the male Slc:Wistar/ST, Jcl:Wistar, and Crj:Wistar rats was bad. Reserpine-induced impairment (RII) in CAR was observed 2-72 h after administration of dopaminergic (DAergic) agents in male Slc:Wistar rats. Amitriptyline (5-80 mg/kg, P.O.), imipramine, desipramine, cis-dosulepine, and trans-dosulepine at dose of 40 mg/kg, P.O. showed no antagonism against RII in CAR 20-23 h after reserpine injection (1 mg/kg, S.C.). However, the atypical antidepressive agents sibutramine (5-10 mg/kg, P.O.), bupropion (40 mg/kg, P.O.), and nomifensine (10-40 mg/kg, P.O.) exhibited antagonism against RII in CAR. The calcium channel antagonists flunarizine, nimodipine, and KP-840 at dose of 10 and 100 mg/kg, P.O., the cerebral improving agent indeloxazine (20-80 mg/kg, P.O.), the anticholinergic agent atropine (5-40 mg/kg, P.O.), 5-hydroxy-L-tryptophan (5-HTP) (40 mg/kg, I.P.), a precursor of 5-hydroxytryptamine (5-HT), and (+/-)-threo-dihydroxyphenylserine [(+/-)-threo-DOPS] (20-200 mg/kg P.O.), a norepinephrine (NE) precursor, showed no antagonism against RII in CAR. The DAergic agents methamphetamine (5 mg/kg, P.O.) and amantadine (50-250 mg/kg, P.O.), L-DOPA (200 mg/kg, P.O.), and the DAergic D1/D2 receptor agonist apomorphine (0.1-1 mg/kg, S.C.) showed marked antagonism against RII in CAR. Although the DAergic D1-receptor agonist KF-38393 (0.3-30 mg/kg, I.P.) and the DAergic D2-receptor agonist quinpirole (0.3-10 mg/kg, I.P.) induced only a weak recovery of RII in CAR when they were administered alone, in contrast to a potent synergistic recovery of RII in CAR, which was observed when SKF-38393 (1 mg/kg, I.P.) and quinpirole (1 mg/kg, I.P.) were administered together. These results suggest that the DAergic nervous system rather than the adrenergic or 5-HT nervous system is involved in RII in CAR, and that both the DAergic D1- and D2-mediated nervous systems play important roles in this process.
Animals↗
Stability of the mandibular position in occlusion of mandibulectomy patients with lateral discontinuity defect.
In mandibulectomy patients with lateral discontinuity defect, the mandible is severely deviated and the occlusion is considered to be unstable. A thorough understanding of the mandibular occlusal position of these patients is important to achieve desirable results in their occlusal rehabilitation. This study compared the stability of the mandibular positions in occlusion, when the opening distance or the biting force was changed during mandibular movements, by simultaneously measuring four points on the mandible three-dimensionally. This study indicated that the mandibular positions in occlusion of these patients were extremely unstable as compared with those of the normal subjects and were considerably different from each other when the opening distance or the biting force was changed during mandibular movements.
Bite Force↗
Direct detection by PCR of Escherichia coli O157 and enteropathogens in patients with bloody diarrhea.
Direct detection of Escherichia coli O157 and foodborne pathogens associated with bloody diarrhea were achieved using polymerase chain reaction (PCR) after the preparation of DNA from stool specimens using the microspin technique. PCR was compared with cultivation and toxin production tests with respect to the efficiency of detection of each pathogen; E. coli O157, Vibrio parahaemolyticus, Salmonella serovar Enteritidis and Campylobacter jejuni. Detection of some or all of the above pathogens in clinical stool specimens was achieved using PCR. The minimum number of cells required for the detection of the above pathogens by PCR was 10(1) CFUs/0.5 g of stool sample. PCR was completed within 6 hr. The above pathogens were also detected in cultivation and toxin production tests. Partial purification of the template DNA using the microspin technique was essential for the elimination of PCR inhibitors from the DNA samples. This PCR method is an accurate, easy-to-read screening method for the detection of Shiga-like toxin producing E. coli O157 and enteropathogens associated with bloody diarrhea in stool specimens.
Bacteria↗
Temporal changes of mRNA expression of matrix proteins and parathyroid hormone and parathyroid hormone-related protein (PTH/PTHrP) receptor in bone development.
Expression of parathyroid hormone and parathyroid hormone-related protein (PTH/PTHrP) receptor is one of the osteoblastic phenotypes; however, it has not been clear whether this phenotype expression is a marker of immature or mature osteoblasts. We examined the temporal expression pattern of PTH/PTHrP receptor in bone development in vivo and in vitro compared with the expression of other osteoblastic phenotypes: osteopontin (OPN), bone sialoprotein (BSP) and osteocalcin (OC), alkaline phosphatase (ALP), and mineralization. Total RNA was extracted from rat calvariae, and cell culture of rat bone marrow at different developmental stages and then Northern blot hybridization were performed. Mineralization was detected with contact microradiography (CMR) in calvaria or with Alizarin Red S staining in bone marrow cell culture. Both in calvaria and in marrow cell culture, extensive expression of OPN, BSP, type I collagen (COL I), and ALP coincided with the onset of mineralization, and OC expression was observed after mineralized tissue formation. Notably, PTH/PTHrP receptor was expressed at an early developmental stage (prenatal day 14 in calvaria, day 5 in culture) when mineralized tissue was not formed and other osteoblastic phenotypes were scarcely detected. Further study in cell culture revealed that the fold increase in cyclic adenosine monophosphate (cAMP) in response to PTH was elevated with the advance in the culture stage. These results indicate that mRNA expression of PTH/PTHrP receptor could be the early differentiation marker in osteoblastic lineage and that the levels of cAMP production in response to PTH represent the stage of osteoblastic differentiation.
Alkaline Phosphatase↗
Effects of short- and long-term dexamethasone treatment on growth and growth hormone (GH)-releasing hormone (GRH)-GH-insulin-like growth factor-I axis in conscious rats.
Although the inhibitory effects of a chronic excess of glucocorticoids (GC) on body growth and GH secretion are well established, the mechanisms involved remain unclear. In this study, we examined the chronic effects of a high dose of dexamethasone (DEX) on spontaneous GH secretion and insulin-like growth factor (IGF)-I in conscious rats. The animals were given daily i.p. injections of DEX (200 microg/day) for either one or four weeks. Body growth assessed by tibia length and serum IGF-I levels was significantly inhibited 1 week after treatment. By contrast, spontaneous GH secretion was not altered 1 week after the treatment. Neither hypothalamic GRH and somtatostain mRNA levels nor GH responses to GRH from single somatotropes were affected 1 week after the treatment. Four weeks after DEX treatment, body growth of the rats was noticeably suppressed. Interestingly, spontaneous GH secretion, hypothalamic GRH mRNA levels and GH responses to GRH were all inhibited 4 weeks after treatment. Pituitary GRH receptor mRNA levels were not altered 1 week after treatment, but increased after 4 weeks. These results indicate that a high dose of DEX initially impairs IGF-I production and subsequently inhibits spontaneous GH secretion in rats. Inhibition of spontaneous GH secretion resulting from chronic GC excess is due, at least in part, to the impairment of hypothalamic GRH synthesis and pituitary GH responsiveness. An increase in the pituitary GRH receptor may be caused by decreased GRH secretion.
Animals↗