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Biomedical subjects

M Sugimura

Publications and source records attributed to M Sugimura.

At least 37 records · Page 2Linked to original sources

Motion of the human mandibular condyle during mastication.

It has been reported that loading to the mandible during closing movement makes the condylar path move more in the superior direction than that during the free closing movement. In this study, the hypothesis was tested that the displacement of the condyle on the chewing side is greater in the direction of the mandibular fossa than that on the non-chewing side. Using a six-degrees-of-freedom jaw movement recording system, we recorded condylar motion in 12 healthy adults without TMD, during the chewing of a large hard gummy jelly. The maximum displacements at the condyle on the chewing side from the maximum intercuspation (CO) position were significantly larger in the superior and medial directions at the initial stage and in the posterior direction at all stages (0.5 mm, 0.5 mm, and 0.6 mm, respectively) than those on the non-chewing side (0.0 mm, 0.1 mm, and 0.1 mm, respectively). This suggests that, in healthy adults, the condyles at CO are located in a position such that excessive load is not applied to the temporomandibular joint when there are the aforementioned displacements.

Adult↗

Enhancement of the in vivo osteogenic potential of marrow/hydroxyapatite composites by bovine bone morphogenetic protein.

A composite of marrow mesenchymal stem cells and porous hydroxyapatite (HA) has in vivo osteogenic potential. To investigate factors enhancing the osteogenic potential of marrow/HA composites, we prepared a bone morphogenetic protein (BMP) fraction from the 4M guanidine extract of bovine bone by heparin-sepharose affinity chromatography. Marrow/HA composites or composites containing marrow mesenchymal stem cells, BMP, and HA (marrow/BMP/HA composites) were implanted subcutaneously in 7-week-old male Fischer rats. BMP/HA composites and HA alone were also implanted. The implants were harvested after 2, 4, or 8 weeks and were prepared for histological and biochemical studies. Histological examination showed obvious de novo bone formation together with active osteoblasts at 2 weeks, as well as more extensive bone formation at 4 and 8 weeks in many pores of the marrow/BMP/HA composites. The marrow/HA composites did not induce bone formation at 2 weeks, but there was moderate bone formation at 4 weeks. At 2 weeks, only marrow/BMP/HA composites resulted in intensive osteogenic activity, judging from alkaline phosphatase and osteocalcin expression at both the protein and gene levels. These results indicate that the combination of marrow mesenchymal stem cells, porous HA, and BMP synergistically enhances osteogenic potential, and may provide a rational basis for their clinical application, although further in vivo experiment is needed.

Alkaline Phosphatase↗

Host plant urease in the hemolymph of the silkworm, Bombyx mori.

Urease activity was detected in the hemolymph of the silkworm, Bombyx mori from the beginning of spinning to the pharate adult stage if the larvae were reared on mulberry leaves throughout the 5th-instar (the last larval instar). In contrast, no urease activity was detected in the hemolymph of insects fed artificial diets, resulting in accumulation of urea during the spinning stage. To identify the hemolymph urease, the enzyme was highly purified from the hemolymph of the spinning larvae that had been reared on mulberry leaves and the properties of the purified enzyme were compared with those of the mulberry leaf urease. Four out of six monoclonal antibodies raised against jack bean seed urease cross-reacted equally with the silkworm hemolymph urease and the mulberry leaf urease. Under reducing conditions, the hemolymph urease and the mulberry leaf urease migrated at 90.5 kDa on SDS-PAGE gels. The first 20 N-terminal sequence of the hemolymph urease revealed complete identity with that of the leaf urease. The optimum pH for activity and Km value for urea were almost the same for the two enzymes. In conclusion, these two ureases are very likely identical, strongly suggesting that the mulberry leaf urease passes through the larval gut wall into the hemolymph without being digested. In addition, oral administration of mulberry leaf urease just before spinning induced considerable urease activity in the hemolymph of the larvae, but the same treatment did not induce enzyme activity in the hemolymph of the larvae three days before the onset of spinning. These results suggest that the silkworm larvae acquire the host plant urease specifically at the end of the feeding stage in order to degrade urea accumulated in the hemolymph.

Journal Article↗

Inhibition of neuronal nitric oxide synthase activity by 3-[2-[4-(3-chloro-2-methylphenyl)- 1-piperazinyl]ethyl]-5, 6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel neuroprotective agent, in vitro and in cultured neuroblastoma cells in situ.

DY-9760e, 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5, 6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate, a novel calmodulin (CaM) antagonist, possesses neuroprotective activity. In the current study, we examined the effects of DY-9760e on nitric oxide synthase (NOS) activities in vitro and on calcium ionophore-induced NO production in situ. DY-9760e inhibited both neuronal NOS and endothelial NOS activities without affecting inducible NOS activity. It also inhibited purified neuronal NOS activity with a potency similar to that seen for purified CaM kinase II activity in vitro. Furthermore, DY-9760e significantly inhibited Ca(2+) ionophore (A23187)-induced NO production in mouse N1E-115 neuroblastoma cells, at a concentration of less than 1 microM. In contrast, no apparent inhibitory effect on Ca(2+)/CaM-dependent protein kinase II activity was observed in cultured hippocampal neurons up to 5 microM. These results suggest that the inhibitory effect of DY-9760e on CaM-dependent NOS activities underlies neuroprotective effects of the agent.

Analysis of Variance↗

Purification and properties of urease from the leaf of mulberry, Morus alba.

Urease was purified from leaves of mulberry (Morus alba, L.) by ammonium sulfate fractionation, acetone fractionation and sequential column chromatography including Q-Sepharose HP, Phenyl-Sepharose HP, Superdex 200 HR and Mono Q. The enzyme was purified 5700-fold to apparent homogeneity with a recovery of 3.6%. The molecular mass of the enzyme was determined to be 90.5 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and 175 kDa by gel filtration, indicating that the enzyme was a homodimer. In the western blot analysis, 90.5 kDa subunit of the mulberry leaf urease cross-reacted with antiserum raised against jack bean seed urease. The N-terminal sequence of the first 20 residues of the enzyme revealed that it has a high similarity (80-90%) to ureases from other plant sources, suggesting that the mulberry leaf urease is closely related to other plant ureases. However, the mulberry leaf enzyme showed an optimum pH for activity of 9.0, while the optimum pH of most ureases isolated from plants and bacterial is neutral. In addition, the K(m) value for urea was 0.16 mM, which is lower than those of ureases from other sources. It is also proposed that urease activity ingested by browsing silkworm releases ammonia that is subsequently used in silkworm protein synthesis.

Amino Acid Sequence↗

Primary non-Hodgkin's lymphoma of the mandible treated with radiotherapy, chemotherapy, and autologous peripheral blood stem cell transplantation.

Extranodal presentation in non-Hodgkin's lymphoma (NHL) is uncommon, and the mandible is very rarely involved. Primary NHL of the mandible, for the most part, has intermediate or high malignancy and has a much greater incidence of local recurrence compared with other sites of involvement. A 48-year-old Japanese man with NHL of the mandible received radiotherapy, followed by high-dose chemotherapy supported with peripheral blood stem cell transplantation (PBSCT). High-dose cyclophosphamide, Adriamycin, and vincristine were used for pretransplant conditioning. He achieved complete remission and has survived in continuous complete remission for more than 72 months to date. Marrow-ablative chemotherapy facilitated by PBSCT is thought to be useful as part of the primary therapy for patients with NHL who have poorer prognoses.

Antineoplastic Combined Chemotherapy Protocols↗

Mutation of the SRC gene in endometrial carcinoma.

Recently, an activating mutation of the SRC gene has been implicated in about one-tenth of advanced colon cancers. The SRC 531 mutation results in truncation of SRC directly C-terminal to the regulatory Tyr 530 and appears to activate the Tyr 530. To investigate whether mutation of SRC plays an important role in the development and progression of gynecological tumors, we performed mutational analysis of the entire coding region of SRC in 70 ovarian carcinomas, 68 endometrial carcinomas and 3 endometrial stromal sarcomas by means of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by nucleotide sequencing and restriction fragment length polymorphism (RFLP) analysis. We found one truncated mutation at codon 531 (Gln to Stop) in an endometrial carcinoma. However, we found no mutation of this gene in ovarian carcinoma or endometrial stromal sarcoma. Our results suggest that mutation of SRC may be implicated in a small proportion of endometrial carcinomas.

Adult↗

A case of a sclerosing stromal ovarian tumor that expresses VEGF.

A case of a sclerosing stromal tumor (SST) of the ovary is presented. One of the tumor's characteristics was its high vascularity. On immunohistochemical staining, the vascular endothelial growth factor (VEGF) was positive for both cellular and edematous areas in the tumor. VEGF was thought to be a factor that affected the clinicopathological features of this tumor.

Endothelial Growth Factors↗

A case of uterine endometrial carcinoma 15 months post-partum.

A case of uterine endometrial carcinoma 15 months post-partum, who did have none of typical risk factors of uterine endometrial carcinoma, is presented. The occurrence of post-partum uterine endometrial carcinoma is extremely rare condition probably due to anti-carcinogenic effects of progesterone. Progesterone refractory cells in the uterine endometrium, which could be an origin of the endometrial carcinoma, might have existed.

Adenocarcinoma↗

Immunohistochemical study of annexin V expression in placentae of preeclampsia.

We investigated the clinical significance of annexin V in the placentae with preeclampsia and found: (1) annexin V was detected on trophoblasts in the placentae and the staining intensity of annexin V in the placentae from such patients was reduced when compared to normal placentae; (2) as expression of annexin V was reduced, the gestosis index from patients with preeclampsia was elevated and the standard deviation value in the infant's standard weight was decreased; plasma level of the fibrin degradation products and thrombin-antithrombin III complex from patients were elevated as the expression of anexin V was reduced. These results suggest that the reduced expression of annexin V in the placentae from patients with preeclampsia may lead to a hypercoagulable state in the intervillous space and may be associated with the development of intrauterine growth restriction.

Annexin A5↗

Effect of food size on the movement of the mandibular first molars and condyles during deliberate unilateral mastication in humans.

To date, the effect of food size on the movement of the mandibular first molars and condyles during chewing has not been fully examined due to methodological problems. The purpose of the present study was to examine the previously unknown effect of food size on masticatory jaw movement. Using a face bow, light-emitting diodes, and optical cameras, we recorded, in 16 young adults with good occlusion, mandibular movement for the first 10 strokes during the unilateral chewing of similarly shaped hard gummy jellies weighing 5 g and 10 g, respectively. The chewing cycle time for the 10-g jelly was significantly longer than that for the 5-g jelly. The jaw-closing and -opening maximum velocities, gapes at the maximum velocities, and maximum gape were significantly faster and larger when 10-g gummy jellies were chewed, compared with results with 5-g jellies, at the mandibular first molar on the chewing side and the condyle on the non-chewing side. With the exception of the velocity, similar tendencies were observed at the molar on the non-chewing side. However, such significant differences were not detected at the condyle on the chewing side. The mandibular first molar on the chewing side was that most affected by food size, and the mean value of the maximum gape coincided approximately with the height of each jelly. These results suggest that humans chew hard coherent food such that the mandibular teeth that come into contact with the food open to a height equivalent to that of the food bolus, and that the changes in movement of the other parts of the mandible are minimized, ensuring efficient mastication.

Adult↗

Epigenetic alterations in methylation in oral squamous cell carcinoma cell lines detected by two-dimensional gel electrophoresis.

It has been described that DNA alterations in human oral squamous cell carcinomas were successfully demonstrated as 6 spots being commonly reduced in more than 50% of 10 lesions using the restriction landmark genomic scanning (RLGS) method. In the present study, the question of whether the DNA alterations involve not only genetic but also epigenetic change was examined with the use of cell lines Ca9-22, HO-1-u-1, HSC-2 and KB and treatment with a demethylating agent 5-aza-2'-deoxycytidine (5-AzaCDR). Intensities of two of the reduced spots were amplified in the cell lines by the 5-AzaCDR treatment, showing that they were due to altered DNA methylation. Our study provides clear evidence that epigenetic changes, like the methylation are related to carcinogenesis in human oral squamous cell epithelium.

Antimetabolites, Antineoplastic↗

[Effects of oral 5-HT3 antagonists on chemotherapy-induced emesis in patients with gynecologic cancers].

The efficacy of an intravenous 5-HT3 antagonist (granisetron) and four oral 5-HT3 antagonists (granisetron, ondansetron, tropisetron and ramosetron) on chemotherapy-induced emesis were investigated in 21 gynecologic cancer patients (63 courses). The severity of emesis after chemotherapy was classified in 4 grades (0: none, 1: slight loss of appetite, 2: severe loss of appetite, but tolerable, and 3: untolerable). The effect of 5-HT3 antagonists was judged by both the score for the severity of the emesis and the frequency of vomiting. The four oral 5-HT3 antagonists were almost the same in efficacy for 5 days after chemotherapy. Oral 5-HT3 antagonists were almost equipotent to intravenous granisetron for JT (paclitaxel + carboplatin) therapy or T (paclitaxel) therapy for 5 days after chemotherapy. However, they were ineffective for CAP (cisplatin + adriamycin + cyclophosphamide) therapy. From these results, oral 5-HT3 antagonists were proved to have a sufficient anti emetic effect after chemotherapy in cases of JT or T therapy. However, in cases of CAP therapy, intravenous 5-HT3 antagonists were thought to be preferable for the control of emesis due to chemotherapy.

Administration, Oral↗

Evaluation of threshold stress for bone resorption around screws based on in vivo strain measurement of miniplate.

The purpose of this study is to investigate the critical threshold stress causing bone resorption evaluated from strain measurement in vivo, comparing the various finite element models. In this study strains of miniplates used for mandibular fractures were measured once a week until the strains reduced. The maximum bite force for each patient was applied in the incisal, right molar and left molar region. The strains increased and reached a peak level at 2-4 weeks, whereas the bite forces increased during the period of measurements. A 3-D osteosynthesis model using finite element method showed that the compressive stresses of the bone surrounding screws ranged within approximately -40 MPa under the condition generating the same amounts of strains measured in the miniplates. Furthermore, various finite element models simulating mandibular reconstruction using the fibular graft were constructed. The models for reconstruction using single strut fibula showed distinct stress concentration in the cortical bone surrounding screws, and the peak stress levels were 2 to 3 times as strong as that of the fracture model. We conclude that critical threshold for bone resorption should be approximately -50 MPa (3600 micro strain).

Journal Article↗

DY-9760e, a novel calmodulin antagonist, reduces brain damage induced by transient focal cerebral ischemia.

Perturbations in Ca2+ homeostasis have been proposed to lead to neuronal damage after cerebral ischemia. DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1- (4-imidazolylethyl)-1H-indazole dihydrochloride 3.5 hydrate) is a novel calmodulin antagonist. In this study, we examined the effects of DY-9760e on brain damage in rats subjected to transient (1 h) focal cerebral ischemia. DY-9760e (0.25-1.00 mg kg(-1) h(-1)) was intravenously infused for 6 h, starting 1 h after middle cerebral artery occlusion. Treatment with DY-9760e 0.25, 0.50 and 1.00 mg kg(-1) h(-1) reduced infarct volume by 30, 42 (P < 0.05), and 60% (P < 0.05), respectively. Furthermore, the effect of DY-9760e on ischemia-induced fodrin breakdown was examined in the same model. Pronounced fodrin breakdown was observed in the cerebral cortex and striatum at 24 h after ischemia. DY-9760e caused potent suppression of fodrin breakdown in the cerebral cortex at the same doses as those that had a protective action against cerebral infarction. From these results DY-9760e may have a therapeutic effect against cerebral ischemic damage in the acute stage.

Animals↗

Oral clonidine reduces the requirement of prostaglandin E1 for induced hypotension.

PURPOSE: To determine the effects of preanesthetic oral clonidine on the dose of prostaglandin EI (PGEI) required to produce hypotension during anesthesia. METHOD: Oral placebo, 75 microg or 150 microg clonidine were administered 60 min prior to induction of anesthesia. Anesthesia was maintained with O2:N2O (30:70) and isoflurane 1.0%. After hemodynamic stabilization, an infusion of prostaglandin EI was started (0.05 microg x kg(-1) x min(-1)) and the rate of infusion was adjusted to maintain mean arterial pressure (MAP) between 60-70 mm Hg during operation. RESULTS: Duration of hypotension in placebo, 75 microg and 150 microg preanesthetic oral clonidine treated groups were 132+/-46, 117+/-37 and 129+/-56 min, respectively. The PGEI requirement in each group were 1563+/-180 (28.6+/-3.2), 594+/-197 (10.8+/-3.6) and 283+/-30 (5.5+/-3.6) microg (microg x kg(-1)), respectively. In addition, blood loss in each group were 1461+/-389, 805+/-240 and 931+/-40 ml, respectively. CONCLUSION: Preanesthetic oral clonidine decreased the dose of PGEI required to produce hypotension, and decreased the blood loss during operation.

Administration, Oral↗

Genetic analysis of familial and multiple malignancies of endometrial cancer.

The presence of the positive replication errors (RER) phenotype in familial and multiple primary malignancies of endometrial cancer, and its association with a poor prognosis was examined. We analyzed 40 endometrial cancers for RER. Eight endometrial cancers with the RER(+) phenotype at multiple microsatellite loci were detected. The presence of the RER(+) phenotype was higher than in non-familial malignancies. None of the eight cases with the RER(+) phenotype involved multiple primary malignancies; however these patients had shorter survival times. In this study, we suggest that RER examination in endometrial cancer may be useful for establishing a diagnosis of a familial malignancy, and for predicting a poor prognosis.

Endometrial Neoplasms↗