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Purpose: We investigated factors contributing to coagulopathy in patients with acute type A aortic dissection (ATAAD) and coagulopathy's influence on patient outcomes. Methods: We grouped 420 patients who underwent ATAAD repair—none under anticoagulation therapy or with liver disease—by the prothrombin time-international normalized ratio (PT-INR) at admission: < 1.2 (no coagulopathy, n = 371), 1.2–1.49 (mild coagulopathy, n = 33), or ≥ 1.5 (severe coagulopathy, n = 16). We then compared the clinical presentation, dissection morphology, and outcomes among the groups. We assessed the PT-INR in relation to the preoperative hemodynamics and searched for factors predictive of a PT-INR ≥ 1.2. Results: The transfusion volume and operation time were increased among patients with coagulopathy (P < 0.05). The in-hospital mortality (15.2–37.5% vs. 5.1%, P < 0.001) and 5-year survival (61.1–74.4% vs. 87.6%) were relatively poor for these patients. The median PT-INR was 1.03 (0.97–1.1) for patients with stable hemodynamics (n = 318), 1.11 (1.02–1.21) for those in shock (blood pressure < 80 mmHg) not given cardiopulmonary resuscitation (CPR) (n = 81), and 1.1 (1.0–1.54) for those in shock given CPR (n = 21) (P < 0.001). A multivariable analysis identified shock (P < 0.001), a partially thrombosed false lumen (P = 0.006), and mesenteric malperfusion (P = 0.016) as predictive variables. Conclusions: Shock, a partially thrombosed false lumen, and mesenteric malperfusion appear to be predictive of dissection-related coagulopathy, which influences outcomes negatively. [ABSTRACT FROM AUTHOR]

Plantago asiatica mosaic virus (PlAMV) is a member of the genus Potexvirus in the family Alphaflexiviridae and has been isolated from a variety of host plants. In particular, PlAMV isolates from ornamental lilies (Lilium spp.) cause necrotic symptoms in these plants, which significantly reduces their commercial value. However, it has not been clear whether PlAMV isolates from other host plants differ in their infectivity and/or pathogenicity to ornamental lilies, and whether growth conditions affect infectivity and pathogenicity. In this study, we inoculated an edible lily species (Lilium leichtlinii) and seven varieties of ornamental lilies with two PlAMV isolates, an isolate from ornamental lily (PlAMV-OL) and an isolate from edible lily (PlAMV-Li1). We found that PlAMV-OL showed higher infection rates and exhibited necrotic symptoms more frequently in lilies than PlAMV-Li1. Moreover, we observed higher infection rates of PlAMV-OL in open field than in greenhouse, and higher rates of necrotic symptoms in autumn test than in spring test, suggesting that growth conditions and season affect infectivity and pathogenicity of PlAMV in lilies. Our study would provide important information for estimating the risk of necrotic disease caused by PlAMV, as well as for cultivation management preventing the occurrence of the disease. [ABSTRACT FROM AUTHOR]

The American cockroach, Periplaneta americana, excretes feces containing aggregation pheromones to attract conspecific individuals. It is thought that these pheromones play an important role in establishing and maintaining colonies. However, despite previous extensive efforts, the aggregation pheromones of P. americana have not been isolated. It is also unclear whether the aggregation pheromones of P. americana are truly biosynthesized by the insect, as most previous experiments extracted chemicals from feces. Here, we investigate the tissue localization of aggregation agents in P. americana. To reduce the effects of diet-derived odorants, we developed a new diet for P. americana consisting of only agar and sugars, and tested the attractiveness of fecal extracts from animals reared on this new diet. Our results show that the aggregation agents of fecal extracts are insect-derived, and the extracts from the midgut evoke stronger behavioral responses than those from other parts of the alimentary tract. This suggests that the midgut may be the production site or the storage organ of the aggregation agents. Thus, our data will facilitate the future identification of the aggregation pheromones of P. americana. [ABSTRACT FROM AUTHOR]

The cultural transmission of behaviour depends on the ability of the pupil to identify and emulate an appropriate tutor1-4. How the brain of the pupil detects a suitable tutor and encodes the behaviour of the tutor is largely unknown. Juvenile zebra finches readily copy the songs of the adult tutors that they interact with, but not the songs that they listen to passively through a speaker5,6, indicating that social cues generated by the tutor facilitate song imitation. Here we show that neurons in the midbrain periaqueductal grey of juvenile finches are selectively excited by a singing tutor and—by releasing dopamine in the cortical song nucleus HVC—help to encode the song representations of the tutor used for vocal copying. Blocking dopamine signalling in the HVC of the pupil during tutoring blocked copying, whereas pairing stimulation of periaqueductal grey terminals in the HVC with a song played through a speaker was sufficient to drive copying. Exposure to a singing tutor triggered the rapid emergence of responses to the tutor song in the HVC of the pupil and a rapid increase in the complexity of the song of the pupil, an early signature of song copying7,8. These findings reveal that a dopaminergic mesocortical circuit detects the presence of a tutor and helps to encode the performance of the tutor, facilitating the cultural transmission of vocal behaviour. [ABSTRACT FROM AUTHOR]

Purpose: Although cervical alignment is better assessed using standing radiography than supine magnetic resonance imaging (MRI), few studies have investigated this. This study aimed to investigate the difference in alignment between standing radiographs and supine MRI images, and assess whether neck position affects the cervical parameters and neurological changes.Methods: We analyzed 53 patients, measuring the O-C2 angle, C2-7 angle (the distinction between the lordotic and kyphotic groups), T1 slope, neck tilt, thoracic inlet angle, and the C2-7 sagittal vertical axis. Inter- and intra-group analyses were conducted to identify any difference between standing radiography and supine MRI. Statistical differences between the cervical parameters were compared.Results: Strong correlations were noted between the equivalent parameters in the radiographs and MRI images, whereas no significant difference was observed in C2-7 angle in the kyphotic group between the radiographs and MRI images, or for neck tilt between the radiographs and MRI images. However, in the lordotic group, the C2-7 angle was significantly different between the two types of images and larger in the radiographs than in the MRI images (C2-7 angle in the radiographs: C2-7 angle in the MRI images: 4.49°, p < 0.001).Conclusions: Neck tilt was a constant parameter. The C2-7 angle in the kyphotic group was similar between the standing radiographs and the supine MRI images; however, the C2-7 angle in the lordotic group was different. Therefore, we recommend that standing cervical radiographs should be preoperatively obtained for all surgical patients. The slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Objective: We previously reported a unique technique called 'less invasive quick replacement (LIQR)' for treating type A acute aortic dissection with moderate hypothermic arrest (28 °C). This study examines the modified LIQR using mild hypothermic arrest (30 °C) with partial retrograde cerebral perfusion (RCP). Methods: 187 patients were divided into 2 groups: group L consisted of 130 patients underwent LIQR without any cerebral perfusion; group M consisted of 57 patients who were treated with modified LIQR. In modified LIQR, circulatory arrest was commenced under the 30 °C for open distal aortic stamp fixation. RCP was used during final half anastomosis of the prosthesis and then rapid re-warming was initiated. Results: The incidence of additional valve or coronary surgeries was significantly higher in group M (28.1%) than in group L (9.2%). The average rectal temperature was significantly higher in group M (29.5 °C) than in group L (27.4 °C). The durations of brain ischemia (M 7.7 min; L 18.6 min), cardiopulmonary bypass (M 82.0 min; L 93.3 min), and overall operation (M 145.2 min; L 154.2 min) were significantly shorter in group M. The incidence of postoperative brain damage was 6 patients (4.6%) in group L, but none in group M. The hospital mortality rate was 3 patients in group L (2.3%). All group M patients were discharged from the hospital without any complications. Conclusion: Modified LIQR is safe and effective. It makes the surgery much quicker and is a less invasive procedure. The surgical outcome was also favorable. [ABSTRACT FROM AUTHOR]

In medical ethics, an appropriate national healthcare system that meets the requirements of justice in healthcare resource allocation is a major concern. Japan is no exception to this trend, and the pros and cons of introducing a two-tier healthcare system (mixed billing system), which permits insured medical care services to be provided along with services not covered by social health insurance, have been the subject of debate for many years. The Supreme Court ruled in 2011 that it was valid for the government to ban mixing medical treatments and both the Ministry of Health, Labour and Welfare and Japanese Medical Association oppose the introduction of such a system. In this paper, we examine the main arguments against the introduction of a two-tier healthcare system and ideas that form their basis, which can be broadly divided into opinions based on the importance of equality and those derived from the logical conclusion that the outcomes would be detrimental. We point out issues and shortcomings of each standpoint and argue that the introduction of the system would not necessarily threaten equality and social solidarity in Japanese society, and that abuses of a self-pay tier would be controllable to a certain extent. Then, the authors-who do not actively promote the introduction of a two-tier healthcare system-conclude that the allegation that is completely devoted to one side (i.e., the importance of equality) and the theory that social healthcare is collapsing, which makes the public excessively nervous, cannot be accepted. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) for patients with aortic stenosis is a less invasive alternative to surgical aortic valve replacement. Despite this, careful anesthetic management, especially strict control of blood pressure and fluid management, is necessary. During TAVI, normalization of left ventricular afterload due to aortic balloon valvuloplasty and prosthetic valve deployment is expected to result in rapid improvement of systolic function and consequent improvement in diastolic function. However, the early effect of TAVI on left ventricular diastolic function is less clear. We hypothesized that TAVI induces a rapid decrease in left ventricular end-diastolic pressure (LVEDP) after valve deployment. This retrospective observational study included 71 patients who had undergone TAVI using the transfemoral approach with a balloon-expandable valve under general anesthesia. Intraoperative LVEDP was measured using an intracardiac catheter. The severity of residual aortic regurgitation (AR) was assessed using the Sellers criteria. The mean (SD) LVEDP was 17.8 (5.3) mmHg just before TAVI and increased significantly to 27.3 (8.2) mmHg immediately after prosthetic valve deployment ( p < 0.0001). The change in LVEDP was 8.7 (8.6) mmHg in patients with low residual AR (Sellers ≤1) and 11.0 (7.1) mmHg in those with high residual AR (Sellers ≥2); however, this difference was not significant. No correlation was found between the LVEDP change and intraoperative fluid balance. In conclusion, LVEDP increased significantly in the early period after valve deployment during TAVI, regardless of residual AR severity. It was suggested that the tolerability of fluid load could be reduced at that time. [ABSTRACT FROM AUTHOR]

A genetic risk score (GRS) was developed for predicting fracture risk based on lifetime prevalence of femoral fractures in 924 consecutive autopsies of Japanese males. A total of 922 non-synonymous single nucleotide polymorphisms (SNPs) located in 62 osteoporosis susceptibility genes were genotyped and evaluated for their association with the prevalence of femoral fracture in autopsy cases. GRS values were calculated as the sum of risk allele counts (unweighted GRS) or the sum of weighted scores estimated from logistic regression coefficients (weighted GRS). Five SNPs (α-ʟ-iduronidase rs3755955, C7orf58 rs190543052, homeobox C4 rs75256744, G patch domain-containing gene 1 rs2287679, and Werner syndrome rs2230009) showed a significant association (P < 0.05) with the prevalence of femoral fracture in 924 male subjects. Both the unweighted and weighted GRS adequately predicted fracture prevalence; areas under receiver-operating characteristic curves were 0.750 [95 % confidence interval (CI) 0.660-0.840] and 0.770 (95 % CI 0.681-0.859), respectively. Multiple logistic regression analysis revealed that the odds ratio (OR) for the association between fracture prevalence and unweighted GRS ≥3 (n = 124) was 8.39 (95 % CI 4.22-16.69, P < 0.001) relative to a score <3 (n = 797). Likewise, the OR for a weighted GRS of 6-15 (n = 135) was 7.73 (95 % CI 3.89-15.36, P < 0.001) relative to scores of 0-5 (n = 786). The GRS based on risk allele profiles of the five SNPs could help identify at-risk individuals and enable implementation of preventive measures for femoral fracture. [ABSTRACT FROM AUTHOR]

Background: DMB-3111 is a biosimilar trastuzumab drug being jointly developed by Meiji Seika Pharma (Japan) and Dong-A Socio Holdings (Korea). We investigated the bioequivalence of DMB-3111 relative to trastuzumab. Objectives: The aim of this study was to investigate the bioequivalence between DMB-3111 and trastuzumab and the pharmacokinetic, safety, and immunogenicity of both drugs in healthy Japanese adult males. Methods: Seventy healthy Japanese adult males were randomized 1:1 to receive either DMB-3111 or trastuzumab as a single intravenous infusion (6 mg/kg) over 90 min. Bioequivalence was assessed in terms of the pharmacokinetic parameters of both drugs. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Immunogenicity was tested using anti-drug antibody (ADA) assays. Results: The 90 % confidence intervals of the treatment differences (DMB-3111 versus trastuzumab) in the mean log-transformed maximum concentration, the area under the concentration-time curves (from 0 min to the last measured value or from 0 min to infinity), mean residence time, and the terminal half-life were within the accepted range for bioequivalence [log(0.80) to log(1.25)]. The frequencies of AEs and adverse drug reactions were similar with both drugs. No ADA reactivity to DMB-3111 or trastuzumab was observed in any subject. Conclusions: DMB-3111, a trastuzumab biosimilar, was bioequivalent to trastuzumab in terms of its pharmacokinetics and showed similar safety after a single intravenous infusion at 6 mg/kg over 90 min in healthy Japanese adult males. DMB-3111 is likely to show similar efficacy and safety profiles to trastuzumab in cancer patients (ClinicalTrials.gov #NCT02100917). [ABSTRACT FROM AUTHOR]

Werner syndrome is a rare autosomal recessive disorder caused by mutations in the human WRN gene and characterized by the early onset of normal aging symptoms. Given that patients with this disease exhibit osteoporosis, the present study aimed to determine whether the WRN gene contributes to the etiology of osteoporosis. A genetic association study of eight non-synonymous polymorphisms in the WRN gene and the incidence of femoral fracture was undertaken in 1,632 consecutive Japanese autopsies in which 140 patients had experienced the fracture during their lifetime. The results were validated in 251 unrelated postmenopausal Japanese women with osteoporosis and 269 non-institutionalized, community-dwelling Japanese adults. A statistically significant association was observed between rs2230009 (c.340G > A)--which results in a Val to Ile substitution--and fracture risk; the incidence of femoral fracture increased dose-dependently with the number of A alleles (p = 0.0120). Femoral neck bone and whole bone densities were lower among postmenopausal women with osteoporosis and community-dwelling adults, respectively, if they were of the AG instead of the GG genotype. The results suggest that Japanese subjects bearing at least one A allele of rs2230009 of the WRN gene are at a significantly higher risk of femoral fracture, possibly due to decreased bone density. [ABSTRACT FROM AUTHOR]

Two novel calcium phosphate cements (CPC) have been developed using calcium sodium phosphate (CSP) as the main ingredient. The first of these cements, labeled CAC, contained CSP, α-tricalcium phosphate (TCP), and anhydrous citric acid, whereas the second, labeled CABC, contained CSP, α-TCP, β-TCP, and anhydrous citric acid. Biopex-R (PENTAX, Tokyo, Japan), which is a commercially available CPC (Com-CPC), and OSferion (Olympus Terumo Biomaterials Corp., Tokyo, Japan), which is a commercially available porous β-TCP, were used as reference controls for analysis. In vitro analysis showed that CABC set in 5.7 ± 0.3 min at 22 °C and had a compressive strength of 86.0 ± 9.7 MPa after 5 days. Furthermore, this material had a compressive strength of 26.7 ± 3.7 MPa after 2 h in physiologic saline. CAC showed a statistically significantly lower compressive strength in the presence of physiologic saline and statistically significantly longer setting times than those of CABC. CABC and CAC exhibited apatite-forming abilities in simulated body fluid that were faster than that of Com-CPC. Samples of the materials were implanted into the femoral condyles of rabbits for in vivo analysis, and subsequent histological examinations revealed that CABC exhibited superior osteoconductivity and equivalent bioresorbability compared with Com-CPC, as well as superior osteoconductivity and bioresorbability compared with CAC. CABC could therefore be used as an alternative bone substitute material. [ABSTRACT FROM AUTHOR]

We have discovered new members of the Pb-based 1222 layered cuprates containing sulfur of (PbS)Sr(RECe)CuO with RE = Sm, Gd, Dy, and Ho. All the samples are of almost-single 1222 phase. From the ρ- T and χ- T measurements, they are found to be superconductors after annealing under 125 atm O atmosphere at 400 °C. Among them, the sample with RE = Gd is found to show superconductivity at the highest temperature of 30 K. [ABSTRACT FROM AUTHOR]

The gum metal with composition Ti-36Nb-2Ta-3Zr-0.3O, is free from cytotoxic elements and exhibits a low elastic modulus as well as high mechanical strength. We have previously demonstrated that this gum metal, once subjected to a series of surface treatments-immersion in 1 M NaOH (alkali treatment) and then 100 mM CaCl, before heating at 700 °C (sample: ACaH-GM), with an optional final hot water immersion (sample: ACaHW-GM)-has apatite-forming ability in simulated body fluid. To confirm the in vivo bioactivity of these treated alloys, failure loads between implants and bone at 4, 8, 16, and 26 weeks after implantation in rabbits' tibiae were measured for untreated gum metal (UT-GM), ACaH-GM and ACaHW-GM, as well as pure titanium plates after alkali and heat treatment (AH-Ti). The ACaH-GM and UT-GM plates showed almost no bonding, whereas ACaHW-GM and AH-Ti plates showed successful bonding by 4 weeks, and their failure loads subsequently increased with time. The histological findings showed a large amount of new bone in contact with the surface of ACaHW-GM and AH-Ti plates, suggesting that the ACaHW treatment could impart bone-bonding bioactivity to a gum metal in vivo. Thus, with this improved bioactive treatment, these advantageous gum metals become useful candidates for orthopedic and dental devices. [ABSTRACT FROM AUTHOR]

New Pb-based 1212 cuprates of (PbW)Sr(NdCa)CuO were synthesized. The sample with x=0.6 was reported to show superconductivity with an onset temperature up to 82 K. Interestingly, in order to obtain superconductivity of the sample, synthesis in N was necessary, then synthesis in air or post-treatment in O led to the disappearance of superconductivity. Recently, we have successfully synthesized new Pb-based 1222 cuprates for the composition range of 0.3≤ x≤1.0 in the (PbW)Sr(EuCe)CuO system. The samples have a tetragonal crystal structure; the typical lattice parameters are a=0.3850 nm and c=2.889 nm. Among them, a sample with x=0.3 is discovered to show superconductivity with an onset of about 15 K. These cuprates have the same (Pb, W)O monolayers as the Pb-based 1212 cuprates described above. In these new cuprates, superconductivity appears when the samples are annealed not in air and under He atmosphere, but under high-pressure O. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to identify mitochondrial DNA (mtDNA) polymorphisms and rare variants that associate with elite Japanese athletic status. Subjects comprised 185 elite Japanese athletes who had represented Japan at international competitions (that is, 100 endurance/middle-power athletes: EMA; 85 sprint/power athletes: SPA) and 672 Japanese controls (CON). The entire mtDNA sequences (16 569 bp) were analyzed by direct sequencing. Nucleotide variants were detected at 1488 sites in the 857 entire mtDNA sequences. A total of 311 variants were polymorphisms (minor allele frequency1% in CON), and the frequencies of these polymorphisms were compared among the three groups. The EMA displayed excess of seven polymorphisms, including subhaplogroup D4e2- and D4g-specific polymorphisms, compared with CON (P<0.05), whereas SPA displayed excess of three polymorphisms and dearth of nine polymorphisms, including haplogroup G- and subhaplogroup G2a-specific polymorphisms, compared with CON (P<0.05). The frequencies of 10 polymorphisms, including haplogroup G- and subhaplogroup G2a-specific polymorphisms, were different between EMA and SPA (P<0.05): although none of these polymorphisms differed significantly between groups after correcting for multiple comparison (false discovery rate q-value0.05). The number of rare variants in the 12S ribosomal RNA and NADH dehydrogenase subunit I genes were also higher in SPA than in CON (P<0.05). Analysis of the entire mtDNA of elite Japanese athletes revealed several haplogroup- and subhaplogroup-specific polymorphisms to be potentially associated with elite Japanese athletic status. [ABSTRACT FROM AUTHOR]

A new family of the Pb-based layered cuprate with the 1222 structure has been synthesized in the (Pb,S)Sr(RE,Ce)CuO (RE=Pr, Nd, Sm, Eu, Gd, Dy, Ho, Er, Tm, and Y) system. The almost-single phase samples are obtained for x=0.25 and y=1.0 in the composition of (PbS)Sr(RECe)CuO. Each of the samples has the crystal structure with a tetragonal symmetry. Both of the lattice parameters a and c are decreasing with the decrease of the ionic radius of RE element. Among these samples, the sample with RE=Er has the smallest resistivity in the whole temperature range and the slope of the resistivity versus temperature is the most gentle. Despite annealing under O atmosphere at high-pressure of 121 atm, this sample is a semiconductor with the transport process characteristics of three-dimensional variable range hopping conduction. Then the samples of RE=Er with smaller y are investigated for the composition of (PbS)Sr(RECe)CuO, the sample with y=0.4 is found to show an onset of resistivity drop phenomenon at about 11 K with the decrease of temperature. Moreover, we also discover that the samples of RE=Ho with y=0.4 show an onset of the resistivity dropping at over 20 K and zero resistivity at 13 K. From these results, the present (PbS)Sr(RECe)CuO system is considered to be a new family of the Pb-based superconducting cuprates with the 1222 structure. [ABSTRACT FROM AUTHOR]

We have synthesized new Pb-based 1222 cuprates containing sulfur in the (PbS)Sr(EuCe)CuO system. X-ray diffraction study shows that almost the single 1222 phase samples can be obtained for a considerable wide area of 0.3≤ x≤1.2 in the composition of (PbS)Sr(EuCe)CuO. Next, the sample with x=0.4 after annealing under high-pressure O is discovered to show an onset of the resistivity drop at about 31 K and to show an onset of diamagnetic signal at about 29 K. These phenomena clearly indicate that the sample is a new superconductor. [ABSTRACT FROM AUTHOR]

We previously reported 2 osteoporosis-susceptibility genes-formiminotransferase N-terminal sub-domain containing gene (FONG) and thrombospondin, type 1, domain-containing 7A (THSD7A)-in which we identified two common single-nucleotide polymorphisms, rs7605378 (FONG) and rs12673692 (THSD7A). The former was associated with a predisposition to osteoporosis and the latter with bone mineral density. To further elucidate the importance of these polymorphisms in the pathogenesis of osteoporosis, we examined their association with the incidence of vertebral fracture. DNA extracted from the renal cortex of 2427 consecutive Japanese autopsies (1331 men, mean age: 79 years; 1096 women, mean age: 82 years) were examined in this study. The presence or absence of vertebral fracture during each subject's lifetime was determined by a thorough examination of the clinical records, as well as autopsy reports. After adjustments for sex and age at autopsy, logistic regression analysis revealed that homozygotes for the risk alleles of rs7605378 (A-allele) or rs12673629 (A-allele) possess an increased risk of vertebral fracture. The subjects simultaneously homozygous for both the risk alleles of rs7605378 (AA genotype) and rs12673629 (AA genotype) showed significantly higher risk of vertebral fracture (odds ratio 2.401, 95% confidence interval 1.305-4.416, P=0.0048) than those who had at least one non-risk allele of either rs7605378 (AC/CC genotypes) or rs12673629 (AG/GG genotypes). The results suggest that Japanese subjects homozygous for the risk alleles of rs7605378 and rs12673629 have a higher risk of vertebral fracture. [ABSTRACT FROM AUTHOR]

Hearing loss (HL) is the most common sensory disorder in humans. Many patients with mitochondrial diseases have sensorineural HL (SNHL). The HL of these patients manifests as a consequence of either syndromic or nonsyndromic mitochondrial diseases. Furthermore, the phenotypes vary among patients even if they are carrying the same mutation. Therefore, these features make it necessary to analyze every presumed mutation in patients with hereditary HL, but the extensive analysis of various mutations is laborious. We analyzed 373 patients with suspected hereditary HL by using an extended suspension-array screening system for major mitochondrial DNA (mtDNA) mutations, which can detect 32 other mtDNA mutations in addition to the previously analyzed 29 mutations. In the present study, we detected 2 different mtDNA mutations among these 373 patients; m.7444G>A in the MT-CO1 gene and m.7472insC in the MT-TS1 gene in 1 patient (0.3%) for each. As these two patients had no clinical features other than HL, they had not been suspected of having mtDNA mutations. This extended screening system together with the previous one is useful for the genetic diagnosis and epidemiological study of both syndromic and nonsyndromic HL. [ABSTRACT FROM AUTHOR]

We previously reported on the synthesis of new Pb-based 1222 superconductor containing phosphorus in the (PbP)Sr(EuCeSr)CuO system. Recently, we have discovered new members of the Pb-based 1222 superconductor containing phosphorus in the (PbP)Sr(LnCeSr)CuO (Ln=Sm and Gd) systems. In each system, it is found that the samples of almost the single 1222 phase can be obtained for a wide composition area of 0.3≤ x≤1.0. After annealing under 143 atm O atmosphere at 400 °C, each sample of Ln=Sm and Gd with x=0.3 is found to show an onset of resistivity-drop at about 28 K and at about 24 K, respectively. Moreover, each samples of Ln=Sm and Gd is found to show an onset of diamagnetic signal at about 25 K and about 22 K, respectively. From these facts, these samples of Ln=Sm and Gd are found to be new members of the Pb-based 1222 superconductor containing phosphorus. [ABSTRACT FROM AUTHOR]

New Pb-based 1222 cuprates containing phosphorus have been synthesized in the (PbP)Sr- (RECeSr)CuO (RE = Nd, Sm, Eu, Gd, Dy, Ho, Er, Tm, Yb, and Y) systems. The almost-single phase samples are obtained for 0.5≤ x≤1.0 and y=0.1 in the cases of RE = Nd, Dy, Ho, Er, Tm, Yb and Y, while for 0.3≤ x≤1.0 and y=0.1 in the cases of RE = Sm, Eu and Gd. The samples crystallize in a tetragonal lattice, the lattice parameters a and c are decreasing with the decrease of the ionic radius of the RE element. Even after annealing under 143 atm O atmosphere at 400 °C, almost all the samples with the common values x=0.5 and y=0.1 are semiconductors with a transport process followed by three-dimensional variable range hopping. However, the samples of RE = Sm, Eu and Gd, which are of almost single 1222 phase, even for x=0.3 and y=0.1, show superconductivity with the onsets at about 25 K, 20 K and 22 K, respectively. Through this study, we find very important procedure for discovery of new superconducting 1222 compound. [ABSTRACT FROM AUTHOR]

We have carried out point contact tunneling measurements by contacting degenerated GaAs semiconductor to polycrystalline samples of NdFeAsOF with T=44−51±1.2. The obtained conductance curves have plural structures included in energy region of the superconducting gap. These structures are seen at almost the same bias positions on every measurement. And as temperature increases, the structures are smeared out. Thus, the structures are attributed to multiple gap structures. The gap values are Δ=6.3±0.3 meV, Δ=12.5±0.5 meV and 2 Δ/ k T=3.1±0.3, 2 Δ/ k T=6.2±0.7. Separately from these multiple gap structures, some fine structures are seen in outer energy region of the gap structures. We have calculated d I/d V and T from using conventional s-wave Eliashberg equations by appropriately assuming α F( ω). The phonon positions of the calculated d I/d V curve are in quite good agreement with that of experimental result. Moreover, the calculated T reproduces the experimental one. [ABSTRACT FROM AUTHOR]

New Pb-based 1212 layered cuprates containing sulfur have been synthesized in the (PbS) Sr (YCa) CuO system. X-ray diffraction analysis shows that the almost single-phase samples are obtained within a region of 0.0≤ x≤0.5. The crystal structure of each sample has a tetragonal symmetry with the typical lattice constants a=0.3837 nm and c=1.186 nm. As Ca content x is increasing, the semiconductor-like behavior is suppressed. But after only annealing under ambient O pressure, none of the samples show any trace of superconductivity. On the other hand, when the samples are annealed under high O pressure of about 13.6 MPa, they show resistivity dropping phenomenon in a region of 0.5≤ x≤0.7. Among them, the lowest resistivity sample with x=0.6 has an onset temperature of the resistivity dropping at about 22.5 K. Moreover, this sample shows a diamagnetic signal at about 21.5 K. These phenomena are attributed to superconductivity. [ABSTRACT FROM AUTHOR]

We already reported on the synthesis of new Pb-based 1212 layered cuprates containing sulfur in the (PbS)Sr(Y,Ca)CuO system. There none of the samples showed superconductivity until after annealing under high O pressure. More recently, we have discovered that the samples could be substituted by Ba for Sr up to x=0.6 in the composition of (PbS)(SrBa)(YCa) CuO. Then if the Ba-substitution is performed for Sr, some of the almost-single phase samples are found to show resistivity drops and magnetic anomalies without annealing under high O pressure. Among the samples, a sample with the nominal composition of (PbS)(SrBa)(YCa) CuO is found to show the highest onset temperatures of a resistivity drop at about 35 K and a magnetic anomaly at about 31.5 K. These are higher than the highest values for the superconducting Ba-free sample of (PbS)Sr (YCa)CuO which was annealed under high O pressure. [ABSTRACT FROM AUTHOR]

The Pb-based 1212 compounds containing phosphorus were already discovered by us in the (Pb,P)Sr(Y,Ca)CuO system. Among the almost-single phase samples, a sample with the nominal composition of (PbP)Sr(YCa)CuO was a superconductor with the highest T of 38 K in the system. Recently, we have been investigating on substitution effect of Ba for Sr on superconductivity in the (PbP)(SrBa)(YCa)CuO system. As a result, it is found that the almost-single 1212 phase samples are obtained in the composition area of 0.0≤ x≤0.4. In this area, with increase of x, the lattice parameters a, c and the cell volume V are found to be gradually increasing. This finding can be considered to show that larger Ba ions certainly occupied the Sr-sites in the sample. However, we obtain such interesting results as that the T value is not so enhanced by the substitution in comparison with that of the sample of x=0.0, and that the maximum value of T was 40 K for x=0.2 and 0.3 at the best. [ABSTRACT FROM AUTHOR]

Studies of the fat mass and obesity-associated (FTO) gene provide compelling evidence of genetic variation in the general population that influences fat levels and obesity risk. Studies of the interaction between genetic and environmental factors such as physical activity (PA) will promote the understanding of how lifestyle can modulate genetic contributions to obesity. In this study, we investigated the effect of FTO genotype, and interactions with PA or energy intake, in young children and adolescents. In all, 1-5-year-old children from the Growth, Exercise and Nutrition Epidemiological Study in preSchoolers (GENESIS) study (N=1980) and 11-18-year-old Greek adolescents (N=949) were measured for adiposity-related phenotypes and genotyped at the FTO single-nucleotide polymorphism (SNP) marker, rs17817449. Adolescents were classified as physically active or inactive based on self-reported levels of PA. In adolescents, FTO genotype influenced weight (P=0.001) and BMI (P=0.007). There was also a significant SNP*PA*gender interaction (P=0.028) on BMI, which reflected the association between FTO genotype and BMI in males (P=0.016), but not females (P=0.15), and significant SNP*PA interaction in males (P=0.007), but not females (P=0.74). The FTO genotype effect was more pronounced in inactive than active males. Inactive males homozygous for the G allele had a mean BMI 3 kg/m2 higher than T carriers (P=0.008). In the GENESIS study, no significant association between FTO genotype and adiposity was found. The present findings highlight PA as an important factor modifying the effect of FTO genotype. [ABSTRACT FROM AUTHOR]

We previously reported on discovery of new Pb-based 1232 cuprate containing boron in the (PbB)Sr(ErCeSr)CuO system. Recently, a new member of the Pb-based 1232 cuprates containing boron has been synthesized in the (PbB)Sr(RECeSr)CuO systems (RE=Ho, Tm, and Y). In each system, almost the single 1232 phase samples are found to be obtained for the composition area of x=1.7-1.9 and y=0.2, and the sample with x=1.7 is found to show the smallest resistivity. Despite of annealing under 142 atm O atmosphere at 400 °C for 4 h, the sample with x=1.7 in each system is a semiconductor with the transport process followed by a three-dimensional variable range hopping conduction. Moreover, it is found that the sample with RE=Ho shows magnetic anomalies at two temperatures of about 11 and 16 K, and the sample with RE=Y shows a diamagnetic signal at about 8 K, respectively. [ABSTRACT FROM AUTHOR]

New Pb-based 1212 compounds containing phosphorus have been discovered in the (PbP)Sr(YCa)CuO system; almost the single 1212 phase samples can be obtained for the composition range of 0.0≤ x≤0.6 and y=0.25. The crystal structure for each sample has a tetragonal symmetry with the typical lattice parameters a=0.3828 nm and c=1.182 nm. Among them, the sample with x=0.6 and y=0.25 shows the onset of resistivity drop at about 39 K and zero-resistivity at about 17 K. Moreover, the sample shows a diamagnetic signal at about 38 K. These phenomena are found to originate from superconductivity with the bulk feature. [ABSTRACT FROM AUTHOR]

New Pb-based layered cuprates containing boron with the 1232 structure have been synthesized in the (PbB)Sr(ErCeSr)CuO system. Nearly the single 1232 phase samples are obtained for the nominal composition of 1.6≤ x≤1.9 and y=0.2. A sample with the composition of (PbB)Sr(ErCeSr)CuO shows resistivity-dropping phenomenon below 10 K and it shows a diamagnetic signal at about 9.0 K, though the superconducting volume fraction is very small. From these results, the sample may well be a new Pb-based superconductor with the 1232 structure. [ABSTRACT FROM AUTHOR]

A T869-->C polymorphism of the transforming growth factor-beta1 (TGF-beta1) gene is reported to be associated with genetic susceptibility to both osteoporosis and vertebral fractures. A low serum 25-hydroxyvitamin D [25(OH)D] level is known to be associated with a higher risk for hip fracture. This study aimed to assess a possible cooperative effect of the gene polymorphism and vitamin D status on vertebral fracture risk. The prevalence of vertebral fracture in 168 postmenopausal female patients with osteoporosis was analyzed, and its association with the TGF-beta1 gene polymorphism and serum 25(OH)D concentration was assessed cross-sectionally. The fracture prevalence increased according to the rank order of the TGF-beta1 genotypes CC < CT < TT, as expected. A significant difference was found not only between the CC and TT genotypes (P = 0.005) but also between the CC and CT genotypes (P < 0.05) when the patients with serum 25(OH)D of more than the median value [22 ng/ml (55 nmol/l)] were analyzed. On the other hand, when those with serum 25(OH)D of less than the median value were analyzed, the protective effect of the C allele against the fracture was blunted; statistical significance in the difference of the fracture prevalence was lost between the CC genotype and the other genotypes. These data suggest that vitamin D fulfillment is prerequisite for the TGF-beta1 genotype in exerting its full effect on the fracture prevalence. [ABSTRACT FROM AUTHOR]

A 50-year-old man presented to a nearby hospital with loss of consciousness. Investigation revealed thrombus formation at the tricuspid valve. Due to suspected pulmonary embolism, the patient underwent contrast-enhanced computed tomography during which he went into a shock with sudden drop in functional oxygen saturation (SpO2). Extracorporeal membrane oxygenation (ECMO) was introduced for cardiovascular and respiratory support, and he was transferred to our hospital for further treatment. The patient was treated by surgical thromboembolectomy and was dismissed from the hospital without major complications. We have experienced a case where ECMO was successfully used for cardiovascular and respiratory support, serving as a bridge therapy between hospitals. [ABSTRACT FROM AUTHOR]

A 41-year-old man who had been previously diagnosed with bicuspid aortic valve presented to our hospital with repeating episodes of fever. Echocardiography revealed vegetation in the bicuspid valve as well as left-to-right shunt, making one suspicious of rupture of the sinus of Valsalva. Under the diagnosis of infective endocarditis of the aortic valve and rupture of the sinus of Valsalva, the patient underwent a surgical operation. Operative findings showed normal sinus of Valsalva; but a communication between the left ventricle and right atrium was present, suggesting a Gerbode defect. The patient was treated by autologous pericardial patch closure and aortic valve replacement and was dismissed from the hospital without major complications. [ABSTRACT FROM AUTHOR]

Sensorineural hearing loss (HL) is one of the most frequent clinical features in patients with mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations, and hearing is impaired in over half of all cases with mitochondrial disorders. This study analyzed 373 patients with suspected hereditary HL using an extensive and rapid suspension-array screening system for 29 major mtDNA mutations, including the m.1555A>G homoplasmic mutation in the MT-RNR1 gene, which causes non-syndromic sensorineural HL and aminoglycoside-induced HL, and the m.3243A>G heteroplasmic mutation in the MT-TL1 gene. This method is rapid and suitable for large-scale screening because universal 96-well plates are available for use, and because an analysis of each plate can be completed within 1 h. This system detected five different mtDNA mutations in 24 of the 373 (6.4%) patients. The m.1555A>G and m.3243A>G mutations were detected in 11 (2.9%) and 9 (2.7%) patients, respectively. In addition, three mutations, that is, m.8348A>G in the MT-TK gene, m.11778G>A in the MT-ND4 gene and 15498G>A in the MT-CYB gene were detected in one patient for each. This screening system is useful for the genetic diagnosis and epidemiological study of both syndromic and non-syndromic HL. [ABSTRACT FROM AUTHOR]

We carried out point contact tunneling measurements by simply contacting degenerate GaAs semiconductor to polycrystalline Ba1− xK xFe2As2 with Tc=31.1±1.0 K. The gap related structure was easily obtained. The gap value 2 Δ determined from peak-to-peak voltage was 18.0 meV, and 2 Δ/ kB Tc was 6.8. Small structures were observed at V∼±23 mV in the conductance curve separately from the gap edge structure. These values are included in phonon energy region and correspond to a peak of phonon density of states. Thus, the structures are attributed to phonon structure. We calculated d2 I/d V2 and Tc, Δ in using Eliashberg equations by assuming α2 F( ω) from neutron phonon spectrum. The first phonon structure in calculated d2 I/d V2 is comparable to experimental one. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) are frequently found in glioblastomas and a high degree of macrophage infiltration is associated with a poor prognosis for glioblastoma patients. However, it is unclear whether TAMs in glioblastomas promote tumor growth. In this study, we found that folate receptor β (FRβ) was expressed on macrophages in human glioblastomas and a rat C6 glioma implanted subcutaneously in nude mice. To target FRβ-expressing TAMs, we produced a recombinant immunotoxin consisting of immunoglobulin heavy and light chain Fv portions of an anti-mouse FRβ monoclonal antibody and Pseudomonas exotoxin A. Injection of the immunotoxin into C6 glioma xenografts in nude mice significantly depleted TAMs and reduced tumor growth. The immunotoxin targeting FRβ-expressing macrophages will provide a therapeutic tool for human glioblastomas. [ABSTRACT FROM AUTHOR]

We report new results from the re-analysis of 672 complete mitochondrial (mtDNA) genomes of unrelated Japanese individuals stratified into seven equal sized groups by the phenotypes: diabetic patients, diabetic patients with severe angiopathy, healthy non-obese young males, obese young males, patients with Alzheimer’s disease, patients with Parkinson’s disease and centenarians. Each phenotype had 96 samples over 27 known haplogroups: A, B4a, B4b, B4c, B*, B5, D*, F1, F2, M*, M7a, M7b, M8, M9, D4a, D4b1, D4b2, D4d, D4e, D4g, D4h, D5, G, Z, M*, N9a, and N9b. A t-test comparing the fraction of samples in a haplogroup to healthy young males showed a significant enrichment of haplogroups D4a, D5, and D4b2 in centenarians. The D4b2 enrichment was limited to a subgroup of 40 of 61 samples which had the synonymous mutation 9296C > T. We identified this cluster as a distinct haplogroup and labeled it as D4b2b. Using an exhaustive procedure, we constructed the complete list of “mutation patterns” for centenarians and showed that the most significant patterns were in D4a, D5, and D4b2b. We argue that if a selection for longevity appeared only once, it was probably an autosomal event which could be dated to after the appearance of the D mega-group but before the coalescent time of D4a, D5, and D4b2b. Using a simple procedure, we estimated that this event occurred 24.4 ± 0.9 kYBP. [ABSTRACT FROM AUTHOR]

Superoxide, which mitochondria mainly produce in vascular endothelial cells, plays an important role in the pathogenesis of atherosclerosis and coronary artery disease. Accordingly, mitochondrial functional differences are thought to be one of the most important factors for the risk of myocardial infarction among various individuals. In the present study, we surveyed mitochondrial haplogroups associated with myocardial infarction in Japanese subjects. The study population comprised 2,137 unrelated Japanese individuals, including 1,181 subjects with a first myocardial infarction (920 males, 261 females) and the control subjects (522 males, 434 females). Twenty-eight mitochondrial single nucleotide polymorphisms of 12 major mitochondrial haplogroups (A, B, D4, D5, F, G1, G2, M7a, M7b, M7c, N9a, and N9b) were determined by use of 28-plex PCR and fluorescent beads combined with sequence-specific oligonucleotide probes. After adjustment for age, sex, body mass index, and prevalence of smoking, hypertension, hypercholesterolemia, and type 2 diabetes, a significantly ( P = 0.0019) lower prevalence of haplogroup N9b was detected in subjects with myocardial infarction than in the controls. Especially, the prevalence of this haplogroup was significantly lower ( P = 0.0007) in the male subjects with the disease than in the male controls. In contrast, there were trends towards higher prevalence of the disease in haplogroup G1 for males ( P < 0.05). No significant haplogroup-related associations were detected for females. Our data suggest that haplogroup N9b confers resistance against myocardial infarction in Japanese males. [ABSTRACT FROM AUTHOR]

The successive electrochemical reduction system using hydrogen-permeable Pd foil electrodes with Pd black catalyst was applied to reduction of nitrate ion. It was revealed that the second metals co-deposited to Pd black catalyst showed an excellent selectivity for decomposition of NO-3 to N2, and was stable for at least 200 days. This system employing a compact and a simple electrolysis cell is expected to be an alternative or a supplement to conventional biological treatments for nitrate removal. [ABSTRACT FROM AUTHOR]

In mitochondria, oxidative phosphorylation and enzymatic oxidation of biogenic amines by monoamine oxidase produce reactive oxygen and nitrogen species, which are proposed to cause neuronal cell death in neurodegenerative disorders, including Parkinson’s and Alzheimer’s disease. In these disorders, mitochondrial dysfunction, increased oxidative stress, and accumulation of oxidation-modified proteins are involved in cell death in definite neurons. The interactions among these factors were studied by use of a peroxynitrite-generating agent, N-morpholino sydnonimine (SIN-1) and an inhibitor of complex I, rotenone, in human dopaminergic SH-SY5Y cells. In control cells, peroxynitrite nitrated proteins, especially the subunits of mitochondrial complex I, as 3-nitrotyrosine, suggesting that neurons are exposed to constant oxidative stress even under physiological conditions. SIN-1 and an inhibitor of proteasome, carbobenzoxy- l-isoleucyl-γ- t-butyl- l-analyl- l-leucinal (PSI), increased markedly the levels of nitrated proteins with concomitant induction of apoptosis in the cells. Rotenone induced mitochondrial dysfunction and accumulation and aggregation of proteins modified with acrolein, an aldehyde product of lipid peroxidation in the cells. At the same time, the activity of the 20S β-subunit of proteasome was reduced significantly, which degrades oxidative-modified protein. The mechanism was proved to be the result of the modification of the 20S β-subunit with acrolein and to the binding of other acrolein-modified proteins to the 20S β-subunit. Increased oxidative stress caused by SIN-1 treatment induced a decline in the mitochondrial membrane potential, ΔΨm, and activated mitochondrial apoptotic signaling and induced cell death in SH-SY5Y cells. As another pathway, p38 mitogen-activated protein (MAP) kinase and exracellular signal-regulated kinase (ERK) mediated apoptosis induced by SIN-1. On the other hand, a series of neuroprotective propargylamine derivatives, including rasagiline [ N-propargyl-1( R)aminoindan]and (−)deprenyl, intervened in the activation of apoptotic cascade by reactive oxygen species-reactive nitrogen species in mitochondria through stabilization of the membrane potential, ΔΨm. In addition, rasagiline induced antiapoptotic Bcl-2 and glial cell line-derived neurotrophic factor (GDNF) in SH-SY5Y cells, which was mediated by the ERK-nuclear factor (NF)-κB pathway. These results are discussed in relation to the interaction of oxidative stress and mitochondria in the regulation of neuronal death and survival in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) coding region polymorphisms, as well as the 150T polymorphism in the noncoding region, have been associated with longevity. We have studied here the association of 150T with longevity further and assessed differences in this association between various mtDNA haplogroups. We analysed a sample of 321 very old subjects and 489 middle-aged controls from Finland and Japan. 150T was more frequent among the very old than among the controls in both the Finnish and Japanese subjects. Interestingly, the association was not similar in all haplogroups, and a stratified analysis revealed that two additional common polymorphisms, 489C and 10398G, modified the association between 150T and longevity. These findings suggest that longevity is partly determined by epistatic interactions involving these three mtDNA loci.European Journal of Human Genetics (2005) 13, 166-170. doi:10.1038/sj.ejhg.5201308 Published online 13 October 2004 [ABSTRACT FROM AUTHOR]

The peripheral blood, spleen, and liver lymphocyte subsets of mice with experimental cheek skin carcinoma were determined. The carcinoma was induced by the topical application of 2% (w/v) 9,10-dimethyl-1,2-benzanthracene (DMBA) to cheek skin twice a week for 12 weeks, and it was examined macroscopically and histopathologically. The composition of lymphocyte subsets (T cells, B cells, CD4+ single-positive [SP] T cells, and CD8+SP T cells) in peripheral blood, spleen, and liver was determined by flow cytometry at 3-week intervals for up to 24 weeks. Spleens and livers were assessed by determining their content of natural killer (NK)T cells. The results showed histopathological progression of the skin lesions from papilloma to squamous cell carcinoma at week 12. Body weight was significantly reduced from weeks 15 to 24, and spleen weight was significantly increased at weeks 21 and 24, but liver weight was not significantly different from the control. The lymphocyte subset composition of peripheral blood showed significant elevation of T cells at weeks 6 and 9, followed by reduced levels at weeks 21 and 24, with significant reduction of B cells at weeks 6 and 9, followed by elevation at weeks 21 and 24. CD4+SP T-cell content was elevated at weeks 6, 9, and 12, and reduced at weeks 21 and 24. CD8+SP T-cell content was significantly reduced at weeks 6, 9, and 12, and elevated at weeks 21 and 24. The composition of the lymphocyte subsets in the spleen was similar to their composition in peripheral blood. The composition of both T and B cells in the liver was significantly different from that in the corresponding control group, but no significant differences were found in either CD4+SP or CD8+SP T cells. These findings revealed that the DMBA-induced cheek skin carcinoma in mice affected not only the lymphocyte subsets in peripheral blood, but the cells in the spleen and liver as well. [ABSTRACT FROM AUTHOR]

Although polymorphism of the mitochondrial DNA 15497guanine/adenine (Mt15497G→A) leads to the Gly251Ser amino acid replacement on human cytochrome b, it is unknown whether functional alteration of the mitochondrion is induced by the Gly251Ser replacement. To see if an association exists between the Mt15497G→A polymorphism and obesity, we examined differences in body size, body composition, and regional body fat distribution between the two genotypes in middle-aged and elderly Japanese individuals (825 women and 906 men). The Mt15497 genotype was determined with an automated colorimetric allele-specific DNA probe assay system using the polymerase chain reaction (PCR) method. The Mt15497G→A polymorphism was detected in 3.5% (n=60) of all subjects: 2.8% (n=23) among women and 4.1% (n=37) among men. After adjusting for age and smoking, we found that body weight, body mass index, waist and hip circumferences, fat mass, fat-free mass, intra-abdominal fat and triglycerides were significantly greater in women with the A allele compared with the G allele (p=0.001–0.025). For men, waist to hip ratio was significantly greater (p=0.032), and waist circumference, intra-abdominal fat and triglycerides had a trend to be significantly greater (p=0.062–0.087) in subjects with the A allele compared with the G allele. These data suggest that the Mt15497 polymorphism may be associated with obesity-related variables and lipid metabolism. [ABSTRACT FROM AUTHOR]

Objective: We studied disease and surgical outcomes in an 80-plus age group to determine the feasibility of cardiac surgery at this age. Methods: Between January 1991 and August 2000, we statistically analyzed 19 variables in 62 consecutive cases of cardiac surgery in the 80-plus age group to predict in-hospital and longterm mortality. Cases were classified by disease type (ischemic heart disease (IHD), n=39; valvular heart disease (VHD) n=19; and mechanical complications associated with acute myocardial infarction, n=4; and by surgical status (emergency, n=6; urgent, n=10; and elective, n=46). We compared these with 370 patients 70 to 79 years undergoing similar procedures during the same interval. Results: No significant difference was seen between groups in total in-hospital mortality—9.7% vs. 3.8%—or in-hospital mortality for IHD—2.6% vs.4.2%—or VHD—10.5% vs.2.8%. We found cardiopulmonary bypass time>150 min. and dialysis to be independent risk factors for hospital death. Actuarial survival at 7.5 years overall was 39% in the 80-plus age group vs. 53% in the 70–79 age group for VHD and 38% in the 80-plus age group vs. 62% in the 70–79 age group. No significant difference was seen in survival between groups for IHD. Stroke proved to be an independent prognostic factor. Conclusions: Cardiac surgery is conducted feasibly in selected octogenarians, providing acceptable mortality and results similar to those achieved in those 70 to 79 years old. [ABSTRACT FROM AUTHOR]

We are currently sequencing the entire mitochondrial genome from 600 persons, including centenarians, patients with Parkinson's disease or diabetes, and young adults with or without obesity to search for single nucleotide polymorphisms (SNPs) associated with longevity or diseases. To test the hypothesis that centenarians are free from deleterious mitochondrial variations, we analyzed amino acid variations in cytochrome b of 64 Japanese centenarians. Although the frequencies of some variations, such as N260D and G251S, differed significantly between centenarians and patients with Parkinson's disease, the most striking feature of centenarian cytochrome b was the much greater scarceness of amino acid variations in contrast with the variety of amino acid replacements in patients with Parkinson's disease. Particular deviations from the standard amino acid sequence may be associated with increased production by mitochondria of reactive oxygen species. The absence of certain variations in centenarians and their presence in patients with Parkinson's disease indicate that these variations do not benefit long-term survival but do predispose to adult-onset diseases and that centenarians are genetically hitting the “golden mean.” [ABSTRACT FROM AUTHOR]

Transforming growth factor-β1 is an important local regulator of bone metabolism, acting downstream of estrogen and cooperatively with vitamin D. The possible association of a C–509→T polymorphism in the promoter region of the transforming growth factor-β1 gene, alone or in combination with a T869→C (Leu10→Pro) polymorphism, with bone mineral density and genetic susceptibility to osteoporosis was investigated in 625 postmenopausal Japanese women. The frequencies of the CC, CT, and TT genotypes of the C–509→T polymorphism in the study population were 24%, 49%, and 27%, respectively. A significant association of C–509→T genotype with bone mineral density was detected: lumbar spine (L2–L4) and total body bone mineral density values were 7% and 5% lower, respectively, in individuals with the TT genotype than in those with the CT or CC genotype. The serum concentration of transforming growth factor-β1 did not vary with C–509→T genotype. Multivariable logistic regression analysis, with adjustment for age, height, body weight, time since menopause, smoking status, body fat mass, and lean mass, revealed a significantly higher frequency of the TT genotype of the C–509→T polymorphism in 286 individuals with osteoporosis than in 170 normal controls. Analysis of combined C–509→T and T869→C genotypes showed that L2–L4 bone mineral density decreases and the prevalence of osteoporosis increases with the number of T alleles. These results suggest that the C–509→T polymorphism, alone or in combination with the T869→C polymorphism, of the transforming growth factor-β1 gene is a genetic determinant of bone mass, and that the number of T alleles in the combined genotype is a risk factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese women. [ABSTRACT FROM AUTHOR]

The pathogenesis of alcoholic cardiomyopathy (ACM) is not well understood. However, recent reports have shown that mutations in mitochondrial DNA (mtDNA) were associated with mitochondrial encephalomyopathy and cardiomyopathy. Our objective was to explore point mutations in mtDNA and the pathogenesis of ACM. We obtained heart biopsy specimens from ten male habitual drinkers with congestive heart failure. We amplified the total mtDNA obtained from these specimens using a two-step polymerase chain reaction method and analyzed the products using automated fluorescence-based direct sequencing. The sequences were compared with those of controls. MtDNA from the ACM patients contained multiple point mutations. Specifically, four of the ten patients carried five point mutations that had been detected previously in several other mitochondrial diseases. These point mutations were not observed in controls. These results suggest that mtDNA abnormalities are involved in the pathogenesis of ACM. [ABSTRACT FROM AUTHOR]