No coding mutations are detected in the peroxisome proliferator-activated receptor-gamma gene in Japanese patients with lipoatrophic diabetes.
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Adolescent↗
Biomedical subjects
H Shinoda
Publications and source records attributed to H Shinoda.
Increased preproenkephalin mRNA and preprotachykinin mRNA in the striatum of Rolling mouse Nagoya.
Although Rolling mouse Nagoya (RMN) has been considered to demonstrate cerebellar dysfunction, our previous metabolic and electrophysiological studies also revealed a dysfunction of the basal ganglia, with the presumable primary site of dysfunction being the striatum. In the present study, we investigated the neurochemical functions of the striatum. In RMN, both preproenkephalin mRNA and preprotachykinin mRNA increased significantly in the striatum, with unaltered GAD mRNA, [(3)H]spiperone binding, [(3)H]QNB binding and preprosomatostatin mRNA, thus indicating the dysfunction of striatal projection neurons. These findings support the hypothesis that the site of primary dysfunction in the basal ganglia is in the striatum of RMN.
Animals↗
Mediation of signal transduction in keratinocytes of human middle ear cholesteatoma by ras protein.
Immunolocalization was used to investigate the distribution of ras protein in both congenital and acquired cholesteatoma tissues. A pathological feature of middle ear cholesteatoma included accumulation of keratin debris due to active proliferation and differentiation of keratinocytes. Ras protein localized to the inner plasma membrane and cytoplasm of keratinocytes in all of the epithelial layers in both congenital and acquired cholesteatoma specimens. Keratinocytes in the basal layer were stained more intensely than their differentiated counterparts. Findings also demonstrated that receptors for epidermal growth factor, fibroblast growth factor, and plateletderived growth factor were present in the plasma membrane of keratinocytes. C-jun, a transcription factor was found in the nuclei of keratinocytes of the cholesteatoma epithelium. These findings indicate that ras protein plays a pivotal role in a signal transduction cascade between growth factor receptors in the plasma membrane and the transcription factor, c-jun, in the nuclei of keratinocytes during the growth of cholesteatoma.
Cholesteatoma, Middle Ear↗
Heat shock proteins in middle ear cholesteatoma.
Heat shock proteins (HSPs), particularly HSP60 and HSP70, may have integral roles in several aspects of the pathogenesis of acquired cholesteatoma. Cholesteatoma is usually associated with an inflammatory reaction occurring in the middle ear cavity, leading to proliferation, differentiation, and programmed cell death of keratinocytes. The presence of HSP60 and HSP70 in cholesteatoma was demonstrated by the immunoblotting assay with specific anti-HSP60 and anti-HSP70 antibodies after protein extraction. The distribution of HSP60 and HSP70 in the cholesteatoma tissues was studied immunohistochemically with paraffin-embedded sections. HSP60 and HSP70 appeared to be localized in the cytoplasm of keratinocytes in all layers of the epithelium of cholesteatoma. Moreover, HSP70 was found in the nucleus of keratinocytes. Both HSPs were not labeled in the epidermis of the external ear canal skin or normal facial skin, except for significant staining on keratinocytes of hair follicles in facial skin. High density of HSP60 and HSP70 may be induced by the inflammatory reaction and immune responses in the middle ear cavity during the clinical development of cholesteatoma. Induction of HSP60 and HSP70 in cholesteatoma epithelium may also be related to hyperproliferation and active differentiation of basal keratinocytes, which cause the accumulation of keratin debris, a characteristic feature of cholesteatoma. In the nucleus of keratinocytes, HSP70 may act to stabilize p53 protein, which functions as a negative regulator of cellular proliferation and is crucial to apoptosis of keratinocytes. This study demonstrates HSPs in cholesteatoma and suggests important roles for HSPs in the clinical development of cholesteatoma.
Adult↗
Application of a newly developed 3-D deformation measurement system to prosthetic dentistry.
A new system for measuring three-dimensional deformation has been developed. The main components of the system are a fixed TV camera and vertically scanning projectors. The advantages of the system are: (1) since there is no mechanical contact between the object and the sensing unit, hardness and form of the object do not have to be considered; (2) the system does not need any precise geometry except for the reproducibility of the vertical scanning stage; (3) the time required for one measurements is extremely short; and (4) the system is not expensive. From the basic experiments for testing accuracy, this system has about +/- 30 microns range deviation against 1000 microns deformation of the object. The system has been applied to investigate the influence of various impression procedures for a removable partial denture on the displacement of the simulated soft mucosal tissue. It is revealed that deformation forms are expressed precisely. Our results suggest that this measurement system is quite useful for research in dentistry and that it could be widely applied.
Biomechanical Phenomena↗
Simplified rapid non-radioactive PCR-SSCP method applied to K-ras mutation analysis.
A newly modified non-RI, PCR-SSCP method is presented and applied to K-ras analysis of colorectal tumors. It comprises five steps: (1) sampling of tiny pieces of fresh solid tissue by scraping with disposable bamboo combs (thin bars made of bamboo, 3 x 3 x 120 mm in size); (2) one-step DNA extraction with lysis buffer containing proteinase K, Nonidet P-40 and Tween 20; (3) PCR with 108 bp, c-ki-ras 2 gene primers; (4) SSCP analysis with 10% formamide-added polyacrylamide gels; and (5) detection with silver staining. In comparison with conventional RI- or non-RI-PCR-SSCP, It can give reliable and clear results in a much shorter time (within a total of 6 h). This novel approach should allow more frequent use of molecular diagnosis in biopsies and surgical pathology.
DNA Mutational Analysis↗
Involvement of platelet cyclic GMP but not cyclic AMP suppression in leukocyte-dependent platelet adhesion to endothelial cells induced by platelet-activating factor in vitro.
1. Incubation of endothelial cells with platelets in the absence or the presence of PAF (10 nM) markedly increased platelet cyclic AMP levels, which were significantly decreased by indomethacin (3 microM). Co-incubation of endothelial cells and platelets with polymorphonuclear leukocytes (PMNs) did not change the platelet cyclic AMP levels. 2. Incubation of endothelial cells with platelets in the absence of PAF increased platelet cyclic GMP levels, which were increased 3.5 fold by PAF. These cyclic GMP levels were significantly decreased by NG-nitro-L-arginine (100 microM), and completely by methylene blue (10 microM). When endothelial cells and platelets were co-incubated with PMNs, the cyclic GMP level in the cell mixture was 42.5 and 65.3% lower than that in endothelial cells and platelets without and with PAF stimulation, respectively. 3. PAF induced platelet adhesion to endothelial cells only when PMNs were present. Methylene blue dose-dependently potentiated the PMN-dependent platelet adhesion induced by PAF, although it had no effect in the absence of PMNs. 4. Sodium nitroprusside and 8-bromo cyclic GMP but not dibutyryl cyclic AMP significantly, although partially, inhibited the platelet adhesion. Inhibition of cyclic GMP-specific phosphodiesterase by zaprinast slightly inhibited the PMN-induced platelet adhesion and potentiated the inhibitory effect of 8-bromo cyclic GMP, while these drugs markedly inhibited the adhesion of platelet aggregates induced by PMN sonicates. 5. These results suggest that the impairment by activated PMNs of EDRF-induced platelet cyclic GMP formation is involved in part in the mechanism of PMN-dependent platelet adhesion to endothelial cells induced by PAF in vitro. The precise mechanism still remains to be clarified.
Animals↗
Uptake and intracellular activity of AM-1155 in phagocytic cells.
The uptake and intracellular activity of AM-1155 in murine J774.1 macrophages and human polymorphonuclear leukocytes were investigated. AM-1155 penetrated phagocytic cells rapidly and reversibly, although the penetration process was not affected by metabolic inhibitors such as sodium fluoride, cyanide m-chlorophenylhydrazone, or ouabain or by nucleoside transport system inhibitors such as adenosine. The intracellular concentration-to-extracellular concentration ratio of AM-1155 in both cell types of phagocytes ranged from 5 to 7. These ratios were almost equal to those for sparfloxacin. The intracellular activity of AM-1155 in J774.1 macrophages, examined with Staphylococcus aureus 209P as a test bacterium, was dependent on the extracellular concentration. AM-1155 at a concentration of 1 microgram/ml reduced the number of viable cells of S. aureus ingested by more than 90%. The intracellular activity of AM-1155 was more potent than those of sparfloxacin, ofloxacin, ciprofloxacin, flomoxef, and erythromycin. These results suggest that the potent intracellular activity of AM-1155 might mainly be due to the high intracellular concentration and its potent in vitro activity.
Animals↗
Inhibitory effect of the topical administration of a bisphosphonate (risedronate) on root resorption incident to orthodontic tooth movement in rats.
Root resorption associated with tooth movement is an unsolved problem in orthodontics. If such root resorption could be prevented, it would be an important contribution toward reducing risk factors in orthodontic treatment. The purpose of this study was to examine the effects of the topical administration of a bisphosphonate, risedronate, which is known to be a potent blocker of bone resorption, on root resorption during tooth movement and on the repair of the resorbed root surface after tooth movement in rats. In the first experiment, both the right and left upper first molars were moved buccally with a standardized expansion spring under administration of risedronate. After day 7, extensive root resorption had occurred on the control side, and the area of root resorption reached a maximum on day 14. The topical administration of risedronate caused a significant and dose-dependent inhibition of root resorption after the orthodontic force was applied. In the second experiment, the right and left upper molars were first moved buccally for 3 weeks. Risedronate treatment began on the day the spring was removed. After the force was withdrawn, the resorbed root surfaces on both the control and risedronate-treated sides were gradually restored by apposition of repair cementum (cementoid). The topical administration of risedronate did not appear to inhibit the repair process of root resorption. These results suggest that the topical administration of risedronate may be useful in preventing root resorption of teeth during orthodontic treatment.
Administration, Topical↗
Congenital stapedial fixation associated with Beckwith--Wiedemann syndrome: two cases of a woman and her brother.
Beckwith-Wiedemann syndrome (BWS) is characterized by the triad of exophthalmos, macroglossia, and gigantism (EMG syndrome) presented at birth. Two patients with BWS, a woman and her younger brother, who presented with conductive deafness caused by middle ear anomaly are reported. Stapedial fixations were confirmed by tympanotomy, and satisfactory hearing improvements were obtained by small fenestra stapedectomy. Hearing loss associated with BWS has not previously been reported. Characteristic sulci on the auricular lobe of BWS are thought to be caused by malposition of the antitragus, which originates from the second branchial arch. Stapedial fixation might be due to maldevelopment of the stapedial lamina, which also originates from the second branchial arch. There could be a causal relationship between stapedial fixation and BWS.
Adolescent↗
[Pharmacokinetic activity of drugs and circadian rhythm].
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Animals↗
Localization of intercellular adhesion molecule-1 in middle ear cholesteatoma.
Intercellular adhesion molecule-1 (ICAM-1) may have a role in acquired cholesteatoma, which is usually associated with an inflammatory reaction occurring in the middle ear cavity. The presence of ICAM-1 in human cholesteatomas was demonstrated by an immunoblotting assay using a specific monoclonal anti-ICAM-1 antibody after protein extraction. Distribution of ICAM-1 in the cholesteatoma tissues was then studied by avidin-biotin-peroxidase complex staining. ICAM-1 appeared to be localized on keratinocytes in all layers of the epithelium and on Langerhans cells in both the epithelium and granulation tissue of cholesteatoma. ICAM-1 was not found in the epidermis of normal external ear canal skin, normal tympanic membrane or normal facial skin, but significant staining was seen on keratinocytes of hair follicles and glands in the facial skin. The present study is the first to demonstrate ICAM-1 in cholesteatoma and suggests that it may have an important role in the clinical development of cholesteatoma, including migration, adhesion and proliferation of lymphocytes, Langerhans cells and keratinocytes.
Cell Adhesion↗
Ontogeny of circadian dentinogenesis in the rat incisor.
Periodic growth increments are found universally in the dentine of animals. The goal here was to determine when and how circadian dentine growth increments develop ontogenetically. A total of 97 rat pups, obtained from 13 mothers of the Wistar strain, were injected with nitrilotriacetato lead at appropriate intervals to chronologically label the dentine. Labelled rat pups were killed 5-50 days after birth. Histological transverse sections of the demineralized dentine were obtained from the maxillary incisors of the pups and stained with haematoxylin. Two types of increments were observed in the circumpulpal dentine. The first type was a deeply stained circadian band which appeared at intervals of about 16-24 microns. The other was a faintly stained, narrow, ultradian increment, at intervals of approx. 6-8 microns. The circadian increments were first detected during the second to third week after birth and were observed consistently afterwards. Before the circadian increments developed, the ultradian increments were predominant. These two rhythms seemed to be independent of each other and sometimes coexisted in one section. Thus, the two types of dentine increments may be due to two independent mechanisms.
Activity Cycles↗
Inhibitory effects of a bisphosphonate (risedronate) on experimental periodontitis in rats.
The present study was designed to examine whether systemic administration of a bisphosphonate, risedronate, could prevent alveolar bone resorption in rats with experimental periodontitis. On Day 1, an elastic ring was placed around the neck of the right mandibular 1st molar to induce inflammatory periodontitis. The animals were given daily injections of either 0.9% NaCl (control group), or 0.8, 1.6 or 3.2 mumoles/kg (s.c.) of risedronate (experimental groups) from Days 1 to 7, and were killed on Day 8. Histological examinations and determination of bone mineral density in the interdental area between the 1st and 2nd molars with an image analyzer revealed that the presence of the elastic ring induced a loss of attachment and bone resorption in the control group. Vigorous bone resorption, with appearance of a large number of osteoclasts, was observed in the interdental and bifurcation areas. In the experimental groups, however, the resorption of alveolar bone and the loss of bone mineral content in these areas were prevented in a dose-dependent fashion, especially at doses of 1.6 and 3.2 mumoles/kg. Many osteoclasts were detached from the surface of the alveolar bone and had degenerated appearances, such as rounded shapes, loss of polarity and pyknosis. These results suggest that administration of risedronate is effective in preventing bone resorption in periodontitis.
Alveolar Bone Loss↗
Circadian rhythm of in vitro bone-resorbing activity in human serum.
Calciotropic hormones as well as biochemical parameters of bone formation and resorption show circadian rhythms. In a previous study in the rat, we observed a circadian rhythm in serum bone-resorbing activity (SBRA). In the present study, we investigated whether there was a circadian rhythm of SBRA in human serum. For this purpose, we studied 10 healthy premenopausal women and 5 healthy men. Blood was collected every 2 h, and urine samples were collected during 4-h periods for 24 h. For the determination of SBRA, media were prepared by reconstituting serum samples with Dulbecco's Modified Eagle's Medium at a ratio of 20% serum and 80% Dulbecco's Modified Eagle's Medium. Limb bones were dissected from 19-day old fetal rats prelabelled with 45Ca and were cultured for 72 h in the presence of the sera. Bone resorption was assessed from the 45Ca released into the culture medium and from that retained in the bone and was expressed as percentage 45Ca release. Serum calcium, phosphorus, PTH, cortisol, and urinary pyridinium cross-links were also determined. SBRA in human serum followed a circadian rhythm with a peak at about 0300 h and a nadir at 0700 h. There was no significant difference between the rhythm of SBRA of women and men. At concurrent time points, SBRA and serum PTH were positively correlated (r = 0.629; P < 0.01), and SBRA and serum cortisol were negatively correlated (r = 0.797; P < 0.01). To further investigate the possible contribution of these hormones to SBRA, either neutralizing anti-PTH antibody or RU-486 (mifepristone), a glucocorticoid receptor antagonist, was added to the serum samples of 6 subjects. Neutralizing the effect of PTH did not change the pattern of SBRA rhythm. The addition of RU-486 had a significant effect on the rhythm of SBRA, reducing the peak and nadir amplitudes. Thus we conclude that cortisol plays a major role in the rhythm of SBRA present in human serum; however, the influence of other factors cannot be excluded. Cortisol may be an important determinant of the circadian rhythm of bone resorption in vivo.
Adult↗
[Inhibitory effects of bisphosphonates on bone resorption].
Bisphosphonates have a P-C-P bond instead of the P-O-P bond of inorganic pyrophosphate that makes them resistant to enzymatic degradation and gives them a high affinity for hydroxyapatite. They are potent blockers of osteoclastic bone resorption and have been successfully used to treat metabolic bone diseases that involve increased bone resorption. It is possible to synthesize a variety of bisphosphonates by substituting the hydrogen on the carbon atom. The pharmacological characteristics and activity varies greatly from compound to compound, ranging from 1 to 10,000. Some structure-activity relationships have been found, but no clear-cut one has been established yet. There is a general consensus that the inhibition of bone resorption by bisphosphonates is not caused by the inhibition of dissolution of the hydroxyapatite crystal, but is actually caused through a cellular mechanism that is not completely understood. In the present review article, the possible mode of bisphosphonate action was discussed with special reference to: (1) whether bisphosphonates inhibit the function of mature osteoclasts directly or through osteoblasts and (2) whether bisphosphonates inhibit the proliferation or differentiation of osteoclast progenitors to osteoclasts.
Animals↗
Expressions of c-jun and p53 proteins in human middle ear cholesteatoma: relationship to keratinocyte proliferation, differentiation, and programmed cell death.
The c-jun protein functions as a transcription factor for many genes, and the p53 protein functions as a negative regulator of cellular proliferation, which is related to the apoptosis pathway that induces DNA damage. It has recently been shown that c-jun promotes keratinocyte proliferation and p53 induces apoptosis of various cells. In this study, the presence of c-jun and p53 in cholesteatoma was demonstrated by immunoblotting assays using polyclonal rabbit anti-c-jun antibody and monoclonal anti-p53 protein antibody, respectively. The cholesteatoma tissue incubated with anti-c-jun antibody showed the staining of keratinocytes on the basal and spinous layers of epithelium. The c-jun protein was localized in the basal layer of normal skin, and the p53 protein was present in the nucleus of keratinocytes in the granular layer of cholesteatoma epithelium. The keratinocytes of normal external ear canal skins and normal human skins were slightly stained in the granular layer of the epidermis. The present findings suggest that c-jun and p53 proteins have a role in keratinocyte differentiation, proliferation, and apoptosis in the cholesteatoma.
Apoptosis↗
Increased prostaglandin I2 and thromboxane A2 production by rat dental pulp after intravenous administration of endotoxin.
The effect of systemic endotoxin (lipopolysaccharide from Escherichia coli 0111:B4) on prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) production by rat dental pulp was investigated. Intravenous injection of endotoxin increased ex vivo production of both PGI2 and TXA2 by the pulp tissue, when determined by radioimmunoassay. A significant effect on PGI2 and TXA2 production was observed with endotoxin doses of greater than 2 and 0.4 mg/kg, respectively. A significant increase was also observed at 30 min after injection of 10 mg/kg endotoxin, reaching a maximum after 60 min for both PG and TX production. Endotoxin (10 mg/kg for 60 min) also increased TXA2 but not PGI2 production in lung tissue, but had no effect in jejunal tissue. Indomethacin (10 microM) completely inhibited PGI2 and TXA2 production by the pulp of physiological saline- and endotoxin-treated rats. Further, arachidonic acids (10 microM) significantly increased PG and TX production by the pulp of saline- but not of endotoxin-treated rats. Endotoxin (100 micrograms/ml) had no in vitro effect on PG or TX production when incubated with isolated pulp, lung and jejunal tissues, suggesting that the endotoxin-induced increases in PG and TX production are an indirect effect. The endotoxin-induced increase in TXA2 production, but not in PGI2 production, by the pulp tissue was significantly suppressed by WEB 2170, a platelet-activating factor (PAF) antagonist. These results indicate that arachidonate metabolism in pulp tissue is susceptible to endotoxaemia in comparison with the lung and jejunum, and further suggest that the endotoxin-induced increase in, at least, TXA2 production by the pulp is mediated by PAF.
Animals↗