Oral symptoms predict mortality: a prospective study in Japan.

Several studies have reported positive associations between oral infections and systemic diseases. The purpose of the present study was to evaluate the effects of oral symptoms on mortality from cardiovascular disease (CVD) and pneumonia. Using data from a cohort study in Japan, we analyzed 4,139 individuals aged 40-79 years. The baseline questionnaire included the following items related to oral symptoms: 'sensitive teeth', 'difficulty in chewing tough food substances', 'bleeding gums', and 'mouth feels sticky'. We used the Cox proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) for mortality, after adjustments for lifestyle, socio-economic factors, and history of diseases. Persons complaining that their 'mouth feels sticky' had a two-fold higher risk of pneumonia (HR = 2.1; 95%CI, 1.2-3.6), while those complaining of 'sensitive teeth' had a lower risk of CVD (HR = 0.4; 95%CI, 0.2-0.9). Some oral symptoms may be predictors of mortality from pneumonia and CVD.

Magnetic and dielectric properties of Yb(Mn1-xAlx)O3 thin films.

Hexagonal RMnO(3) is known as one of the candidates for multiferroic materials. We have focused on YbMnO(3), which has ferroelectricity along the c axis below 1000 K and antiferromagnetic ordering below 80 K. We have reported that magnetic, field-induced ferromagnetism in YbMnO(3) epitaxial thin films. In this study, we investigate the substitutional effect of the nonmagnetic element, Al, for Mn ions with triangular spin ordering on the ferroelectric and magnetic properties of YbMnO(3).

Sequence of critical events involved in fusion of phospholipid vesicles induced by clathrin.

Membrane fusion induced by clathrin is accompanied by several events such as conformational change, membrane binding and association of clathrin, and membrane aggregation (Maezawa et al. (1989) Biochemistry 28, 1422-1428; Maezawa and Yoshimura (1990) Biochem. Biophys. Res. Commun. 173, 134-140). To clarify the sequence of these events, we examined their time-courses by reducing the pH of the medium from 7.4 to a given pH in the range of 3.5-5.0 at 25 degrees C or 10 degrees C. Large unilamellar vesicles composed of phosphatidylserine and phosphatidylcholine were used in most experiments. The half-time for conformational change of clathrin was less than those for membrane binding and association of clathrin. The half-times and the initial rates of membrane binding and association of clathrin were similar order of magnitude, although the pH-profiles of the initial rates of the two events were somewhat different. Membrane aggregation started after membrane binding of clathrin. A lag phase was observed in the time-course of membrane fusion, whereas there was no lag phase in membrane binding and association of clathrin and membrane aggregation. Moreover, the lag time before fusion was independent of the clathrin concentration, although the initial rates of these three events were dependent on it, suggesting that the three reactions are not responsible for the lag phase before fusion, and that there is some other event(s) in the lag time. On the other hand, there was a threshould-pH in the pH profile of the lag-time and the threshold-pH coincided with the critical pH at which the final associated state of clathrin was apparently reversed in the presence and absence of liposomes, suggesting that the event(s) in the lag phase may be related to this final associated state of clathrin molecules on the liposome membranes. These results indicate that clathrin-induced fusion of liposomes is initiated through the following sequential events: conformational change of clathrin, membrane binding and association of clathrin, which occur simultaneously but independently, membrane aggregation, an event(s) in the lag phase, and actual fusion.

Sodium-induced aggregation of phosphatidic acid and mixed phospholipid vesicles.

Sodium-induced aggregations of sonicated vesicles prepared from synthetic phosphatidic acid and from its 1:1 mixtures with synthetic phosphatidylethanolamine and phosphatidylcholine were studied by turbidimetric measurements. The aggregation reactions were almost completely reversible on change in the Na+ concentration, pH or temperature. The threshold concentrations of Na+ for aggregations of pure dipalmitoylphosphatidic acid vesicles and mixed dipalmitoylphosphatidylethanolamine- and dimyristoylphosphatidylcholine-dipalmitoylphosphatidic acid vesicles were found to be 200, 310 and 550 mM, respectively, at 25 degrees C and pH 7.2. The hydrocarbon chain lengths of phosphatidic acid and phosphatidylethanolamine had little effect on the threshold concentrations. The threshold concentrations for phospholipid vesicles composed of phosphatidic acid alone or its 1:1 mixture with phosphatidylethanolamine were changed by varying either the pH or temperature, while that for phosphatidylcholine-phosphatidic acid vesicles was almost independent of the pH and temperature, implying that aggregation of the latter vesicles is induced by a somewhat different mechanism.

Interaction of clathrin with liposomes: pH-dependent fusion of phospholipid membranes induced by clathrin.

Clathrin, dissociated from coated vesicles of bovine brain and purified by gel chromatography, was found to interact with the lipid bilayer as shown by the spontaneous release of encapsulated fluorescent dye in liposome. Clathrin-induced dye release was enhanced at acidic pH in phosphatidylserine-containing vesicles. A strong correlation between dye release and fusion of liposomes was observed. In general, when there was a fast release of encapsulated dye induced by clathrin, a pH-dependent, clathrin-induced fusion was observed. Clathrin did not induce either dye release or fusion of egg phosphatidylcholine liposomes. The self-association of clathrin at low pH diminished the fusogenic activity. Fusion induced by clathrin at low pH could be stopped at pH above 5.0 and resumed by lowering the pH below 5.0. This suggests that the interaction of clathrin with phospholipid membranes can be regulated by pH.

Relationship between the amount of rice oil ingested by patients with yusho and their subjective symptoms.

The goal of this study was to clarify the subjective symptoms closely related to yusho by examining the relationship between the amount of PCB-contaminated rice oil ingested by patients and the subjective symptoms recorded on their questionnaires. The amount of PCB-contaminated rice oil consumed by the patients was obtained by interviewing the housewife in each yusho family. Individual consumption of the oil was estimated by taking into account age, sex and the number of meals at home. In 1970, 46 patients were available for analysis, and in 1971, 33 patients were available. Among 12 subjective symptoms studied, numbness of the limbs, coughing, expectoration, and the sensation of "elevated" teeth were considered to show a dose-response relationship, which suggests that these subjective symptoms are closely related to yusho. Consistent high rates of complaints of general fatigue and eye discharge were considered possibly to be connected with yusho, although no dose-response relationships have been determined. Other subjective symptoms, such as fever, headache, dizziness, abdominal pain, swelling in the joints, changes in menstruation, and loss of hair failed to show consistent dose-response relationships. It should be noted, however, that for these symptoms which failed to show dose-response relationships, it is impossible to deny a causal relationship.

Asian hereditary neuropathy patients with peripheral myelin protein-22 gene aneuploidy.

Japanese hereditary neuropathy with liability to pressure palsy (HNPP) patients have a deletion of one peripheral myelin protein-22 (PMP22) gene region in distal chromosome band 17p11.2 as do Caucasian patients. Japanese and Asiatic Indian CMT1A patients have a PMP22 gene duplication that results in Charcot-Marie-Tooth disease type IA (CMT1A; HMSNIA) in patients of European and Middle Eastern ancestry. About 70% of Japanese CMT1 patients have a PMP22 duplication as do Caucasians, while Japanese CMT1B, CMT2 and Dejerine-Sottas patients to not have PMP22 gene region aneuploidy. Although HNPP and CMT1A genotypes are generated simultaneously by unequal recombination that results in PMP22 gene aneuploidy in each daughter cell, only 3 Japanese HNPP probands with PMP22 deletion from a large patient population were referred to a single center compared to 18 referred CMT1A probands with PMP22 duplication. This lower HNPP frequency more likely reflects lower HNPP reproductive fitness than patient ascertainment bias because disease severity and variation in severity is about the same in CMT1A and HNPP patients and because all patients of both types were referred regardless of disease severity. These results, along with an apparently high de novo CMT1A mutation rate, suggest that common ancestors of Japanese, Asian Indians, and Caucasians carried PMP22 geneflanking sequences that enhance unequal crossing over.

Exposure of hydrophobic domains of clathrin in its membrane fusion-inducible pH region.

Clathrin induces fusion of phospholipid membranes containing phosphatidylserine when the pH of the medium is reduced below about 6. The hydrophobicity of clathrin in the membrane fusion-inducible pH region was examined. In the presence of clathrin, the fluorescence maximum of 1-anilinonaphthalene-8-sulfonate was shifted to shorter wavelengths and its fluorescence intensity increased at pH values below about 6. Steep increase of the fluorescence intensity of the fluorescent probe, N-(1-anilinonaphthyl-4)maleimide covatently bound to clathrin was observed in a similar pH region. The efficiency of resonance energy transfer from tryptophan to anilinonaphthyl residues in the clathrin molecule showed similar pH dependency. When Triton X-114 solutions containing clathrin were subjected to phase separation by raising the temperature from 0 degree to 30 degrees C at different pH values, clathrin remained in the aqueous phase above pH 6, whereas the protein was partitioned between the aqueous and detergent phases at pH 5-6, and was present only in the detergent phase below pH 5. The effective hydrophobicity of clathrin determined by the fluorescence method using cis-parinaric acid also increased at pH values below 6. Moreover, clathrin was aggregated by lowering the pH below 6. These results show that exposure of hydrophobic domains of clathrin through conformational change occurs in its membrane fusion-inducible pH region, suggesting the crucial role of protein hydrophobicity in the initiation of membrane fusion.

Kinetic analysis of endocytosis and intracellular fate of liposomes in single macrophages.

Endocytosis and the intracellular fate of liposomes in single mouse peritoneal macrophages were examined kinetically by fluorescence microphotometry. Liposomes labeled with N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine or containing 8-amino-naphthalene-1,3,6-trisulfonate were promptly incorporated into macrophages on incubation at 37 degrees C, but fluorescence increase caused by hydrolysis of 4-methylumbelliferyl-beta-D-glucoside encapsulated in the liposomes was observed after 30 min of incubation. The fluorescences of calcein and 8-hydroxy-1,3,6-pyrenetrisulfonate (HPTS) in liposomes, which were respectively quenched statically due to high concentration and dynamically by a co-entrapped fluorescence quencher, p-xylene-bis-pyridinium bromide, also increased from 30 min after the start of liposome incorporation, indicating that macrophages require this period for intracellular delivery of liposomes from the cell surface to lysosomes. Measurement of the intraendosomal pH change in a single macrophage at 37 degrees C with liposomes containing a pH-sensitive fluorescent marker, HPTS, showed that the pH value decreased continuously to a constant value of 5.5 in 30-40 min after endocytosis, and this decrease was reversed on addition of NH4Cl, suggesting that acidification of endosomes is not a stepwise reaction and is coupled with delivery of liposomes. These fluorescence microphotometric systems using liposomes containing different fluorescent dyes should be useful for kinetic analyses of the endocytosis and intracellular fate of liposomes in various phagocytes.

Fusion of phospholipid vesicles induced by clathrin: modulation of fused liposome size.

The effects of lipid composition, temperature, and ionic strength on critical events in the membrane fusion reaction induced by clathrin, such as membrane binding and self-association of clathrin, membrane aggregation, and actual fusion, and the size of fused liposomes, were examined using large unilamellar vesicles (LUV) containing acidic phospholipids. When membrane fusion and aggregation of LUV with different lipid compositions were initiated at 25 degrees C in 0.1 M NaCl by lowering the pH of the medium from 7.40 to 4.75 in the presence of clathrin, two types of reaction processes were observed: fusion and aggregation of LUV containing phosphatidylserine and phosphatidic acid occurred slowly with a long fusion lag-phase and reached a high level, whereas the two reactions of LUV containing phosphatidylglycerol and phosphatidylinositol were induced faster with a much shorter fusion lag-time and leveled off in a shorter time. Similar differences in the fusion reactions were observed in media at different temperatures and ionic strengths with any type of LUV: slow and extensive aggregation and fusion occurred at low temperature and/or high ionic strength, but faster, less extensive reactions occurred at high temperature and/or low ionic strength, indicating that the two types of reaction pattern are due to the dependencies of the aggregation and fusion reactions on the temperature and ionic strength, but not on the lipid composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the N- and C-terminal domains of bovine beta 2-glycoprotein I in its interaction with cardiolipin.

beta 2-Glycoprotein I (beta 2-GPI) is a cofactor in the recognition of the phospholipid antigen cardiolipin by anti-cardiolipin antibodies in autoimmune diseases such as systemic lupus erythematosus. We examined the interactions of various forms of bovine beta 2-GPI, such as its intact form, desialylated form (Asialo-beta 2-GPI), N-terminal domain (Domain I), and modified forms of beta 2-GPI and Asialo-beta 2-GPI with nicks in their C-terminal domains, with phospholipid liposomes under different conditions of pH and ionic strength. We found that at neutral pH and low ionic strength, beta 2-GPI became bound to liposome membranes containing cardiolipin, phosphatidylglycerol, phosphatidylserine, phosphatidylserine, phosphatidic acid, or phosphatidylinositol, but not phosphatidylcholine alone. The number of phospholipids involved in the binding seemed to depend on the head group structure of the negatively charged phospholipids, but the dissociation constant did not, being about 10(-8) M, except that for the interaction with phosphatidylinositol, which was one order of magnitude lower. We also found that Domain I and Asialo-beta 2-GPI bound to liposome membranes containing negatively charged phospholipids, and that in the interaction with cardiolipin, their dissociation constants were about 10(-6) and 10(-8) M, respectively. At neutral pH and both low and high ionic strengths, the affinities of the nicked forms of beta 2-GPI and Asialo-beta 2-GPI for cardiolipin were both lower than those of their intact forms but similar to that of Domain I.(ABSTRACT TRUNCATED AT 250 WORDS)

Structure and function of the recombinant fifth domain of human beta 2-glycoprotein I: effects of specific cleavage between Lys77 and Thr78.

In order to elucidate the mechanism of binding of beta 2-glycoprotein I (beta 2-GPI) to cardiolipin (CL), we constructed a high-level expression system for the C-terminal domain (Domain V) of beta 2-GPI using Pichia pastoris and studied its conformation and liposome-binding activity. Purified Domain V was found to have the native disulfide bonds. It had a compactly folded conformation, judging from the circular dichroism spectrum, and exhibited a cooperative unfolding transition induced by pH or urea. Also, it bound liposomes containing CL. Commercially available human beta 2-GPI is known to be selectively cleaved between Lys 317 and Thr 318. We found that bovine factor Xa weakly but specifically cleaves the corresponding site of recombinant Domain V, i.e., the peptide bond between Lys 77 and Thr 78. The conformation of the "nicked" Domain V, which was cleaved at this site, was examined by circular dichroism and fluorescence measurements, and concluded to be similar to that of the intact protein. The stability of the nicked Domain V to urea was slightly lower than that of the intact protein. Although both Domains V bound to liposomes containing CL, the affinity of the nicked Domain V was greatly reduced in comparison with the intact protein, indicating that the cleavage of the peptide bond between Lys 77 and Thr 78 controls the binding to CL. In addition, analysis of the fluorescence spectra in the presence and absence of CL liposomes indicated that Trp 76 is involved in the binding site. These results suggest that the region including Trp 76, Lys 77, and Thr 78 has a critical role in binding to CL.

Investigation of the mineralocorticoid and hypertensinogenic activity of 18-hydroxycortisol in conscious sheep.

The increased urinary excretion of 18-hydroxycortisol (18-OHF) in patients with primary aldosteronism has raised the possibility that 18-OHF is involved in the maintenance and/or pathogenesis of the associated hypertension. This study has investigated the mineralocorticoid, glucocorticoid, and hypertensinogenic activities of 18-OHF in the conscious sheep. Infusion of 18-OHF (400 micrograms/h i.v. 5 days; n = 5) alone had no effect on blood pressure or on fluid and electrolyte balance. Infusion of a combination of five adrenal steroids (aldosterone 3 micrograms/h, cortisol 5 mg/h, corticosterone 0.5 mg/h, 11-deoxycortisol 1 mg/h and deoxycorticosterone 25 micrograms/h, i.v. 5 days; n = 5) increased blood pressure by 14 +/- 1 mmHg (p < .001), but when 18-OHF was infused together with the five adrenal steroids, no additional increase in blood pressure was observed. In another group of sheep (n = 4) 18-OHF was infused at a range of doses (5, 50, 100, 200, 500, and 1000 micrograms/h i.v.), each for 2 h, into sodium-replete and sodium-deplete, adrenalectomized sheep. 18-OHF had no effect on the urinary sodium or potassium excretion or on the salivary Na/K ratio in either group as compared with vehicle infusion. To examine the renal effects of 18-OHF, a range of doses of 18-OHF (5, 50, 100, 200, 500, and 1000 micrograms/h) were infused directly into the renal artery of conscious sheep (n = 4). 18-OHF did not affect the renal blood flow nor the urinary sodium or potassium excretion compared with vehicle infusion. In summary, we could not demonstrate any mineralocorticoid, glucocorticoid, or hypertensiongenic effects of 18-OHF in conscious sheep at a dose of 400 micrograms/h. Thus, a cautious approach to interpreting the role that 18-OHF plays in the clinical manifestations of primary aldosteronism, is necessary.

DNA-binding characteristics of aclarubicin as compared with daunorubicin and doxorubicin.

The effect of ionic strength on aclarubicin - DNA complexes was studied in comparison with its effect on daunorubicin - or doxorubicin - DNA complexes, using the spectrophotometric method. The hypochromic shift of aclarubicin, induced by its binding to native DNA, decreased to a lesser extent by the addition of Na+ than those of daunorubicin and doxorubicin, which suggests that aclarubicin-native DNA complexes are the most stable at high ionic strength. Similar examinations were made with heat-denatured DNA and polyvinyl sulfate (PVS). Aclarubicin-denatured DNA complexes showed a greater decrease in the hypochromic shift by the addition of Na+ than the corresponding complexes with native DNA. However, for daunorubicin and doxorubicin, there were no significant differences between the complexes of anthracyclines with native and denatured DNAs. In addition, the hypochromic shift of aclarubicin-PVS complexes decreased more prominently by the addition of Na+ than those of daunorubicin - and doxorubicin - PVS complexes. These results suggest that the electrostatic interaction of aclarubicin with DNA is more labile than that of daunorubicin and doxorubicin, since anthracyclines bind to single-stranded DNA and polyelectrolytes primarily by electrostatic interaction. Therefore, the other types of interaction, which may be stronger than that of daunorubicin and doxorubicin, seem to be associated with the higher stability of aclarubicin-native DNA complexes at high ionic strength. The structural differences between aclarubicin and daunorubicin or doxorubicin are considered to contribute to the differences in DNA-binding characteristics observed in this study.

Evaluation of oral health promotion in the workplace: the effects on dental care costs and frequency of dental visits.

UNLABELLED: An oral health promotion program has been conducted since 1989 at a shipyard in Japan. AIMS: The purpose of the present study was to assess the impact of oral health promotion in the workplace in terms of dental care costs and frequency of dental visits. METHODS: This program consisted of orientation, an initial regimen, and group counseling. The initial regimen included an evaluation of each participant's oral health status, and instruction concerning oral hygiene, and prevention of oral disease. The participants were selected with each unit being a preexisting peer group. Eighty-seven participants were compared with 216 control subjects in terms of annual dental care costs and frequency of dental visits in four periods: the 1-year period before the program, the 1st year after the program, the 2nd year after, and the 3rd year after. RESULTS: The annual mean dental care cost in the participant group for the year prior to the program was higher than that in the control group (21,317 vs. 17,116 yen). In the 1st year after the program, the difference increased (26,642 vs. 19,481 yen). In the 2nd and 3rd years after the program, dental care costs in the participant group were lower than those in the control group (2nd year: 18,305 vs. 22,841 yen, 3rd year: 16,911 vs. 21,920 yen). CONCLUSIONS: It can be concluded that this oral health promotion program in the workplace contributed to saving of costs associated with dental care. The workplace can be regarded as a key area for implementation of an oral health care system to make good use of limited resources.

Replacement of myocardium with a Dacron prosthesis for complications of acute myocardial infarction.

From July 1983 to April 1986, four patients (three with ventricular septal perforations and one with left ventricular free-wall rupture) underwent replacement of the myocardium with a Dacron prosthesis for complications of acute myocardial infarction. There were three males and one female, ages ranging from 53 to 70 years (mean 63.3). Three of the four patients survived; the one with the ventricular septal perforation died of severe cardiac failure five days after operation. Replacement of the infarcted myocardium with a Dacron prosthesis seems to be an excellent operative technique for the treatment of complications of acute myocardial infarction when the left ventricular cavity is predicted to be small after resection of the myocardium.

[A case of Behçet's disease presenting cerebral infarction due to occlusions of the bilateral internal carotid arteries].

This is a case report of a 41-year-old man with Behçet's disease who suffered from cerebral infarction due to complete occlusions of the bilateral internal carotid arteries. His illness began at age 23 with blurred vision of the right eye. The last few years he complained of recurrent painful ulcers on the mucosa or skin of the mouth and the external genitalia. In August 1998, he was admitted to our hospital in an acute confusional state with right hemiplegia. Head CT scans and MRIs revealed acute and subacute ischemic lesions in the left frontal lobe and some other regions of the bilateral hemispheres. Carotid angiography showed complete occlusions of the bilateral internal carotid arteries just rostral to the bifurcations. He did not have any histories of hypertension nor other risks for cerebrovascular diseases. Although direct evidence for the cause of carotid occlusions was not obtained, we speculated that his cervical lesions came from the arterial changes attributable to vasculo-Behçet's disease. Vascular involvements are not infrequent in Behçet's disease, but we believe such occlusive lesions in the bilateral internal carotid arteries as seen in our case are extremely rare. As a construction worker he had undergone a lot of mechanical stress on his neck, which might be a trigger for the carotid lesions.

[Effect of worksite dental health program on periodontal status--evaluation by CPITN and bleeding on probing at each tooth].

A dental health promotion program which aimed to prevent periodontal disease was carried out at a shipyard in Nagasaki Prefecture. Repeated tooth cleaning instruction and prophylaxis were conducted in order to adopt proper oral hygiene habits. The first 3 months of this program included 'Initial instruction,' and 'Regular instruction' were given every 6 months in following 2 years. The oral examination was carried out before and after Initial instruction, and at each Regular instruction. The effect of this program was evaluated by 2 measures: CPITN and Bleeding on probing. After this program, the rate of teeth with pockets 4 -5 mm deep or deeper (CPITN 3, 4) was decreased. In contrast, the rate of teeth with no sign of periodontal disease (CPITN 0) was increased remarkably: the percentage increased from 8% preinitial instruction to 40% with regular instruction. Both the rate and grade of teeth with bleeding on probing were decreased. These results indicated that this program was helpful in improving the periodontal status. CPITN and Bleeding on probing at each tooth as an evaluation measure made our analysis more detailed.

Post-surgical unilateral temporomandibular joint dislocation treated by open reduction followed by orthodontic treatment.

A case of prolonged unilateral temporomandibular joint (TMJ) dislocation, which was treated by open surgical reduction and post-surgical orthodontic therapy, is presented. A 58-year-old woman presented complaining of facial asymmetry and malocclusion. She had received surgery for a malignant tumour in the right retromolar region 7 years previously. It was considered that contraction of the pterygoid muscle by surgical injury caused anterior meniscal displacement and TMJ dislocation. Since manual manipulation failed, direct open reduction was performed after separation of the lateral pterygoid muscle from the condylar head and removal of the intra-articular scar tissues. Although the condylar head was returned to the glenoid fossa, optimal occlusion was not obtained because of compensatory tooth movement and inclination. Satisfactory occlusion and symmetric facial appearance were brought about by post-surgical orthodontic therapy.