Professional dental care provision systems for persons with disabilities by prefecture in Japan.

OBJECTIVE: The number of persons with disabilities has increased and aged. Although it is important to maintain good oral health to extend healthy life expectancy, it is difficult for such people. This study aimed to analyze regional disparities in dental care provision systems for disabled people and to propose measures for the establishment of an appropriate system. BASIC RESEARCH DESIGN: To examine regional disparities in dental care provision systems for persons with disabilities, the number of practicing dentists and dental clinics per 100,000 population, dentists certified by the Japanese Society for Disability and Oral Health, and institutions with certified dentists per 100,000 disabled persons for each prefecture were calculated. The Gini coefficient of each was also calculated to visualize and analyze regional disparities. RESULT: The Gini coefficients were 0.09 and 0.07 for practicing dentists and dental clinics and 0.32 and 0.28 for the certified dentists and institutions with the certified dentists, respectively. Dental institutions for the disabled abounded in the three metropolitan areas: Tokyo, Aichi, and Osaka, and their density tended to be lower in northern and southern Japan. In prefectures with few such institutions, there was no correlation between the number of institutions and prefectural residents' income, and some prefectures had similar incomes but had many institutions. CONCLUSION: The distribution of dental care to the disabled is highly uneven in Japan, therefore, a system needs to be established to address this issue.

Geographic distribution of dental specialists permitted to advertise dental practices in Japan.

OBJECTIVE: The purpose of this study was to determine the geographic distribution of dental specialists permitted to advertise dental practices in Japan. METHOD: We identified the populations of 349 secondary medical zones nationwide from the 2015 population census, as well as the number of dentists in five specialties, namely oral surgeons, pedodontists, periodontists, dental anesthesiologists, and dental radiologists, who had been permitted to advertise dental practices, from a 2016 survey of physicians, dentists, and pharmacists. We determined the placement rate, Lorenz curve, and Gini coefficient for dentists in each specialty in order to describe their geographic distributions. RESULTS: The placement rates of at least one of these types of dentist in each secondary medical zone were 73.9% for oral surgeons, 66.2% for pedodontists, 60.5% for periodontists, 31.8% for dental anesthesiologists, and 18.3% for dental radiologists. The Gini coefficients were 0.397, 0.400, 0.491, 0.650, and 0.761, respectively. CONCLUSION: The dentists in each specialty were few in number and were unequally distributed among the zones, but less so for oral surgeons and pedodontists. Dental anesthesiologists and radiologists were located primarily at university hospitals in urban areas and, therefore, were more unequally distributed.

Trends in the geographic distribution of dental clinics in Japan.

AIM: In Japan, along with the increase in the number of dentists, the number of dental facilities has continuously increased as well. This study aimed to examine whether the increase in the number of dental clinics in Japan has led to an improvement in their geographic distribution. METHODS: We analysed the number of dental clinics and population in all municipalities in Japan as of 2000, 2005 and 2010. We obtained data on the population from the population census and data on the number of dental clinics from the Survey of Medical Institutions. The number of municipalities was 3,258 in 2000 but had dropped to 1,750 by 2010 due to municipal mergers so population and dental data for other years were recalculated based on 2010 municipal boundaries. Lorenz curves and Gini coefficients were used to assess the distribution of dental clinics per 100,000 persons. RESULTS: The mean number of dental clinics per 100,000 persons among all municipalities was 49.9 in 2000, 52.2 in 2005 and 53.4 in 2010. The Gini coefficient for the clinics in the whole country was 0.172 in 2000, 0.164 in 2005 and 0.153 in 2010. CONCLUSION: The results suggest that the regional inequalities in the availability of dentists have been reduced gradually as the number of dental clinics has increased.

Introduction and evaluation of computer-assisted education in an undergraduate dental hygiene course.

OBJECTIVE: This paper introduced newly developed computer-assisted learning materials and reports of a survey of junior college dental hygiene students who have used them. METHODS: We authored new educational material to promote students' basic dental hygiene practice skills using a simulation software generator. A set of five developed materials were tested by 43 female second-year dental hygiene students during the second semester at a college in Chiba, Japan. The evaluation was conducted in the form of a questionnaire including open-ended questions. Students' opinions were analysed using characteristic diagrams, a troubleshooting tool that can be used to visually illustrate the causes and effects of a problem. RESULT: The overall results of the evaluation were positive. The students were given five sets of simulation learning materials (SLMs). Eighty-three percent of the students felt that they could carry out independent study of clinical practice better after the virtual practice. Ninety-three percent of them felt that the exercises should be continued in the future, and eighty-eight percent of them felt that this virtual practice deepened their interest in other classes and training sessions. All of the students found the virtual practice beneficial for their learning. DISCUSSION: The present results suggest that the students became conscious of their lack of knowledge through SLMs. These findings indicate that SLMs for practicing basic clinical procedures is beneficial.

Lymphatic architecture of the human gingival interdental papilla.

Many studies have investigated the lymphatic architecture of head and neck using experimental animals, confirming the existence of lymphatic networks beneath the epithelium in gingival tissue. In this study, we investigated the use of these lymphatics as a drug delivery route by studying the architecture of lymphatic vessels in human interdental papilla. Serial cryosections were cut using the film-transfer method. To identify lymphatics, the sections were stained using enzyme histochemical and immunohistochemical techniques and three-dimensional images of lymphatics were reconstructed using 3D visualization software. Capillary lymphatic networks were observed in the lamina propria beneath the epithelium in human interdental papilla, and they joined with lymphatic networks beneath the epithelium in free gingiva. The networks consisted of a single layer of large irregular, hexagonal meshes and precollecting lymphatic vessels heading toward collecting lymphatic vessels that exited on the periosteum of the alveolar crest. These findings suggest that lymphatic flow from the interdental papilla drains into collecting lymphatic vessels running buccolingually on the alveolar crest of the interdental papilla. This may be an important anatomical feature during inflammation throughout the oral cavity in that the drainage function is maintained by part of lymphatic flow that is not impaired during the healing process.

[Coronary artery bypass in octogenarians; how to reduce operative mortality and enhance long-term quality of life].

Octogenarians are at increased risk for perioperative morbidity and mortality after coronary artery bypass. This study is aimed to elucidate the suitable operative strategy and perioperative management. A retrospective analysis was conducted of 54 consecutive patients with 80-years of age or older, who underwent elective isolated coronary artery bypass between May 1999 and May 2008. Mean follow-up was 43.3 months and 96.3% complete. Operavive mortality was 3.7% and the incidence of stroke was 3.7%. The 7-year cardiac survival was 80.4% and the 7-year cardiac event free was 65.0%. The use of arterial graft to the right coronary artery was identified as independent predictor of late cardiac event. Neither total arterial revascularization nor bilateral internal thoracic artery grafting was a significant cardiac event factor. This retrospective study suggests a benefit of the less invasive strategy in terms of operative mortality and morbidity. Application of fast-track treatment in octogenarians appears to be an effective approach to reduce perioperative morbidity and enhance long-term quality of life.

Novel etodolac analog SDX-308 (CEP-18082) induces cytotoxicity in multiple myeloma cells associated with inhibition of beta-catenin/TCF pathway.

We have reported previously that R-enantiomer of etodolac (R-etodolac), which is under investigation in phase 2 clinical trials in chronic lymphocytic leukemia, induces potent cytotoxicity at clinically relevant concentrations in multiple myeloma (MM) cells. In this study, we demonstrated that SDX-308 (CEP-18082), a novel analog of etodolac, has more potent cytotoxicity than R-etodolac against both MM cell lines and patient MM cells, including tumor cells resistant to conventional (dexamethasone, doxorubicine, melphalan) and novel (bortezomib) therapies. SDX-308-induced cytotoxicity is triggered by caspase-8/9/3 activation and poly (ADP-ribose) polymerase cleavage, followed by apoptosis. SDX-308 significantly inhibits beta-catenin/T-cell factor pathway by inhibiting nuclear translocation of beta-catenin, thereby downregulating transcription and expression of downstream target proteins including myc and survivin. Neither interleukin-6 nor insulin-like growth factor-1 protect against growth inhibition triggered by SDX-308. Importantly, growth of MM cells adherent to bone marrow (BM) stromal cells is also significantly inhibited by SDX-308. Our data therefore indicate that the novel etodolac analog SDX-308 can target MM cells in the BM milieu.

[Effects of dexmedetomidine hydrochloride on postoperative sedation in cardiovascular surgery].

BACKGROUND: Postoperative assessment of brain damage in cardiovascular surgery is often obscured by sedatives. Therefore, early postoperative detection of brain attack and its treatment are also hampered. A newly approved sedative, dexmedetomidine hydrochloride has weak analgesic effect and no respiratory depressive effect. These characteristics allow early assessment of brain damage after surgery. In this report, we compared 2 sedatives, propofol and dexmedetomidine hydrochloride, in cardiovascular settings. SUBJECT AND METHODS: Both sedatives were initiated right after admission to the intensive care unit (ICU), followed by titrimetric method targeting for the sedation agitation scale (SAS) from 1 to 4. Thirty-five cases were included in dexmedetomidine hydrochloride group (DEX group) and 16 cases were included in propofol group (Prop group). RESULTS: Preoperative and operative demographic data were the same between the 2 groups. Conversion rate to another sedatives, and incidence of vasopressor or hypotensor use were both in the same proportion in both groups. Intubated time was the same in both groups. Both systolic and diastolic blood pressures were kept lower in DEX group than Prop group until 8 hours after ICU admission. Other hemodynamic measurements, heart rate, pulmonary artery pressure and cardiac index showed no statistical difference. SAS and Ramsay score were better in DEX group early after ICU admission, and remained better until 10 hours later. CONCLUSION: Dexmedetomidine hydrochloride has no major hemodynamic nor other side effects after cardiovascular surgery. Dexmedetomidine hydrochloride could be used as an effective agent for postoperative sedation and analgesia in cardiovascular settings.

[Aortic valve replacement in elderly patients with small aortic annulus; is the indexed effective orifice area important?].

We sought to determine whether the small indexed effective orifice area (EOAI) increased mortality and morbidity after aortic valve replacement (AVR) in patients over 75 years of age. From May 1999 to July 2005, 77 patients underwent isolated AVR for aortic stenosis. They were divided into 3 groups (S-EOAI : EOAI < or = 0.7 cm2/m2, M-EOAI : 0.7 cm2/m2

on the extracellular sheath of dermal melanocytes in nevus fusco-ceruleus acromiodeltoideus (Ito) and Mongolian spot. An ultrastructural study.

The dermal melanocytes in the lesions of nevus of Ito and Mongolian spot were shown to possess the extracellular sheath composed of both fine filaments and granules (2-5 nm in diameter). In the case of nevus of Ito, the granular component appeared to predominate in the shealth, which measured up to 3 micrometers in width and was estimated to cover about 97% of the total surface of dermal melanocytes. No ultrastructural changes were appreciable on the melanocyte shealth in nevus of Ito according to the difference in the age of patients (39 and 64 years), or in the lasting period of the dermal melanocytosis. By contrast, the melanocyte sheath in the case of Mongolian spot was much less developed than in nevus of Ito, predominantly filamentous in texture, and showed a marked decline with advance of the age of infants (from 2 mo to 6 yr). Many of the dermal melanocytes in Mongolian spot showed a partial disruption of their cytolemma, resulting in discharges of melanosomes free into the connective tissue matrix. Significance of these findings was discussed in relation to the differtial fate of melanocytes within the human dermis.

Temperature-dependent change of serological specificity of Candida albicans NIH A-207 cells cultured in yeast extract-added Sabouraud liquid medium: disappearance of surface antigenic factors 4, 5, and 6 at high temperature.

The cells of Candida albicans NIH A-207 strain (A-strain) cultivated in YSLM at high temperatures (37 and 40 degrees C) did not undergo agglutination with the factor sera 4, 5, and 6 in a commercially available factor serum kit, 'Candida Check', and formed a grape-like shape. The mannans isolated from the cells had lost their reactivity against the factor sera in ELISA. It was also revealed by 1H NMR analysis that the mannans contained neither a phosphate group nor a beta-1,2-linked mannopyranose unit, although these mannans increased the non-reducing terminal alpha-1,3-linked mannopyranose unit. The cells and the mannans prepared by cultivation at such high temperatures followed by 27 degrees C in the same medium entirely recovered the reactivity with the factor sera.

NMR assignment of the galactomannan of Candida lipolytica.

The chemical structure of the cell wall galactomannan of Candida lipolytica was analyzed using two-dimensional NMR techniques without chemical fragmentation. The H-1-H-2-correlated cross-peaks of the galactomannan indicated that it consists of an alpha-1,6-linked mannan backbone moiety with side chains. A sequential NMR assignment of the side chains through nuclear Overhauser effect (NOE) cross-peaks indicated that the triose side chain contains an alpha-1,2-linked galactopyranose unit at the non-reducing terminal. The structure was significantly different from the galactomannan of Trichophyton. The molar ratio of the side chains calculated from the H-1 signal dimensions indicated that ca. 45% of the backbone alpha-1,6-linked mannose units are not substituted with side chains and are responsible for the reactivity of the galactomannan with factor 9 serum.

Detection of beta-1,2-mannosyltransferase in Candida albicans cells.

A particulate insoluble fraction from Candida albicans J-1012 (serotype A) strain cells was obtained as the residue after extracting a 105,000 x g pellet of cell homogenate with 1% Triton X-100. Incubation of this fraction with a mannopentaose, Man beta 1-->2Man alpha 1-->(2Man alpha 1-->)(2)2Man (alpha beta Man5), in the presence of GDP-mannose followed by high performance liquid chromatography showed the formation of a mannohexaose. Analysis of the product by 1H NMR indicates that alpha beta Man5 was changed to Man beta 1-->2Man beta 1-->2Man alpha 1-->(2Man alpha 1-->)2 2Man (alpha beta Man6). This beta-1,2-mannosyltransferase (ManTase) II activity was completely inhibited by Zn2+ and was not restored by the addition of EDTA. The corresponding enzyme fraction from C. albicans NIH B-792 (serotype B) strain cells, the mannan of which does not possess both the alpha beta Man5 and alpha beta Man6 side chains, also exhibited the same beta-1,2-ManTase II activity.

Identification of the antigenic determinants of factors 8, 9, and 34 of genus Candida.

We investigated the antigenic determinants of factors 8, 9, and 34 of the genus Candida among pathogenic yeasts by enzyme-linked immunosorbent assay (ELISA) using mannans of Saccharomyces cerevisiae wild type and mutant types, mnn 1-mnn 4 and mnn 2. Results of ELISA including antisera against the antigenic factors of genus Candida (Candida Check, latron; FAbs) indicated that these three types of mannan distinctly react with FAbs 34, 8 and 9, respectively. To identify the recognition sites of these FAbs, we compared the ability of various oligosaccharides to inhibit the binding of the mannans to FAbs. The results indicated that FAb 34 preferentially recognizes linear side chains containing a non-reducing terminal alpha-1,3-linked mannose residue, Man(alpha)1 --> 3Man(alpha)1 --> (2Man(alpha)1 --> )n(2Man) (n > or = 0), and that one of the recognition sites of FAb 9 is linear alpha-1,6-linked oligomannosyl series, Man(alpha)1 --> (6Man(alpha)1 --> )n(6Man) (n > or = 2). On the other hand, the recognition site of FAb 8 apparently consisted of two alpha-1,2-linked oligomannosyl side chains and an alpha-1,6-linked mannose residue that originated from the mannan backbone, Man(alpha)1 --> 2Man(alpha)1 --> 2(Man(alpha)1 -->2Man(alpha)1 --> 6)Man.

Production of anti-peptide specific antibody in mice following immunization with peptides conjugated to mannan.

In order to investigate the usefulness of polysaccharides as carriers for the induction of antibody to synthetic peptides, peptides representing residues 139-147 of the surface antigen of hepatitis B and residues 129-140 of the pre-S2 region of the protein were coupled to mannan and dextran via an aminocaproic spacer molecule. Of the two conjugates studied, only mannan was useful as a carrier for the efficient production of anti-peptide antibodies.

Calpain inhibitor causes accumulation of ubiquitinated P-glycoprotein at the cell surface: possible role of calpain in P-glycoprotein turnover.

P-glycoprotein (Pgp) is a plasma-membrane glycoprotein that confers multi-drug resistance (MDR) on cells and displays ATP-driven drug pumping. The possible contribution of calpain-mediated proteolytic pathways to the functional regulation of the Pgp molecule was evaluated using K562/DXR, MDR cells. N-Acetyl-L-leucyl-L-leucyl-norleucinal was effluxed by Pgp, but N-benzyloxycarbonyl-L-leucyl-L-leucinal (zLLal), an inhibitor of calpain, retarded the degradation of Pgp leading to accumulation of the molecule largely at the cell surface membrane. Treatment with brefeldin A did not obstruct the zLLal-induced Pgp accumulation. NH4Cl increased the cytoplasmic Pgp level, with a slight to significant decrease at the cell surface membrane. Ubiquitin-ELISA and western blot analysis confirmed that the Pgp molecule, which accumulated mainly at the cell surface, was ubiquitinated. However, lactacystin did not show any accumulation of Pgp in either the cytoplasm or the cell surface membrane, suggesting that the proteasome did not participate in the phenomenon. Additionally, the Pgp was limitedly proteolyzed by calpain into two 98 kDa and 69 kDa, fragments within one minute. Despite the increased accumulation of Pgp at the cell surface after treatment with calpain inhibitor, the cytoplasmic doxorubicin level of the cells treated with a calpain inhibitor was higher than that of non-treated cells and approached that of parental cells. These results indicated that calpain involved Pgp turnover and that calpain inhibition induced ubiquitinated Pgp-accumulation mainly at the cell surface membrane with a reduction in its own functions suggesting that the modulation of Pgp-turnover involves MDR-reversal by another approach.

Studies on phospholipases from Streptomyces. III. Purification and properties of Streptomyces hachijoensis phospholipase C.

1. Phospholipase C [EC 3.1.4.3] found in the growth medium of Streptomyces hachijoensis was purified about sixty-fold by dialysis and column chromatography on Sephadex G-50. 2. The active fraction was separated by isoelectric focusing into two fractions, phospholipase C-I (pI 6.0) and phospholipase C-II (pI 5.6). 3. Both purified phospholipases C were homogeneous by immunodiffusion and were not differentiated as regards antigencity. 4. Phospholipase C-I had maximal activity at pH 8.0 and the optimal temperature was 50degree. Phospholipase C-I was stable at 50degrees for 30 min and was stable at neutral pH. 5. The activity of phospholipase C-I was inhibited by high concentrations of various detergents such as Triton X-100, sodium, cholate, SDS and was also inhibited by Ca2+, Ba2+, Al3+, and EDTA, but was stimulated by Mg2+, and ethyl ether. 6. The Km value of phospholipase C-I was 0.9 mM, using phosphatidylcholine as a substrate. 7. By the gel filtration procedure, the molecular weights of phospholipase C-I and -II were both determined to be 18,000. 8. Phosphatidylcholine, phosphatidylinositol, cardiolipin, sphingomyelin, and lysophosphatidylcholine were hydrolyzed by phospholipase C-I, but phosphatidylethanolamine and phosphatidylserine were hydrolyzed with difficulty under the same conditions, Phospholipase C-I also hydrolyzed phosphatidic acid.

Studies on phospholipases from Streptomyces. II. Purification and properties of Streptomyces hachijoensis phospholipase D.

1. Phospholipase D [EC 3.1.4.4] from Streptomyces hachijoensis was purified about 570-fold by column chromatography on DEAE-cellulose and Sephadex G-50 followed by isoelectric focusing. 2. The purified preparation was found to be homogeneous both by immunodiffusion and polyacrylamide disc gel electrophoresis. 3. The isoelectric point was found to be around pH 8.6 and the molecular weight was about 16,000. 4. The enzyme has maximal activity at pH 7.5 at 37 degrees. The optimal temperature is around 50 degrees at pH 7.5, using 20 min incubation. 5. The enzyme was stable at 50 degrees for 90 min. At neutral pH, between 6 and 8, the enzyme retained more than 95% of its activity on 24 hr incubation at 25 degrees. However, the enzyme lost 80% of its activity under the same conditions at pH 4.0. 6. The enzyme was stimulated slightly by Ca2+, Mn2+, and Co2+, and significantly by Triton X-100 and ethyl ether. It was inhibited by Sn2+, Fe2+, Fe3+, Al3+, EDTA, sodium dodecyl sulfate, sodium cholate, and cetylpyridinium chloride. 7. This phospholipase D hydrolyzes phosphatidylethanolamine, phosphatidylcholine, cardiolipin, sphingomyelin, phosphatidylserine, and lysophosphatidylcholine, liberating the corresponding bases. 8. The Km value was 4mM, determined with phosphatidylethanolamine as a substrate.

Studies on sterol-ester hydrolase from Fusarium oxysporum. I. Partial purification and properties.

1. A search for a long chain fatty acyl sterol-ester hydrolase in microorganisms led to the isolation from soil of five strains belonging to Fusarium sp. which produced strong activity in the culture medium. 2. The cholesterol esterase from Fusarium oxysporum IGH-2 was purified about 270-fold by means of CaCl2 precipitation and Sephadex G-75 column chromatography. 3. The cholesterol esterase was activated by adekatol and Triton X-100. It was inhibited by lecithin and lysolecithin, and completely inactivated by heat treatment (60 degrees C for 30 min, at pH 7.0). 4. The optimum pH of the enzyme was found to be around 7.0. 5. Among various cholesterol esters tested, cholesterol linoleate was the most suitable substrate. 6. Cholesterol esters in serum were also hydrolyzed by this enzyme.

Lysosomal glycogen accumulation in rat liver and its in vivo kinetics after a single intraperitoneal injection of acarbose, an alpha-glucosidase inhibitor.

A single intraperitoneal injection of acarbose (400 mg/kg) into rats caused lysosomal accumulation of glycogen in the liver, mimicking the cytological characteristics of human glycogen storage disease type II (Pompe's disease). The animal model is therefore useful for studying the pathogenesis of the disease. In the present study, we applied this model to examine the lysosomal hydrolytic pathway of glycogen in vivo. To quantify the lysosomal glycogen, the lysosome-rich fraction was rapidly prepared from liver homogenate by agglutination in the presence of Ca2+. Then the fraction was treated with alpha-amylase in isotonic medium to remove cytosolic glycogen, followed by transfer to hypotonic conditions in the presence of Triton X-100 to destroy total glycogen. The amount of lysosomal glycogen was calculated from the difference between the glycogen levels measured before and after the treatment under hypotonic conditions, and then it was corrected based on measurements of the intactness (%) of lysosomes and the recovery (%) of the lysosomal marker enzyme (beta NAGase). We observed no measurable lysosomal glycogen in normal liver by this method, and this was confirmed by electron microscopy. After administration of acarbose, the lysosomal glycogen level increased to 2.5 mg/g liver within 2 days, and then decreased gradually at a rate of 0.4 mg/day/g. The accumulation of glycogen in the lysosomes at an initial velocity of 1.5 mg/day/g liver may be considered as the amount of glycogen that would normally be degraded by acid alpha-glucosidase. Therefore, assuming that the liver breaks down about 40 mg glycogen/day/g, we estimated that about 3% of the glycogen would be hydrolyzed by the lysosomal pathway.