Thermal and impact histories of 25143 Itokawa recorded in Hayabusa particles.

Understanding the origin and evolution of near-Earth asteroids (NEAs) is an issue of scientific interest and practical importance because NEAs are potentially hazardous to the Earth. However, when and how NEAs formed and their evolutionary history remain enigmas. Here, we report the U-Pb systematics of Itokawa particles for the first time. Ion microprobe analyses of seven phosphate grains from a single particle provide an isochron age of 4.64 ± 0.18 billion years (1σ). This ancient phosphate age is thought to represent the thermal metamorphism of Itokawa's parent body, which is identical to that of typical LL chondrites. In addition, the incorporation of other particles suggests that a significant shock event might have occurred 1.51 ± 0.85 billion years ago (1σ), which is significantly different from the shock ages of 4.2 billion years of the majority of shocked LL chondrites and similar to that of the Chelyabinsk meteorite. Combining these data with recent Ar-Ar studies on particles from a different landing site, we conclude that a globally intense impact, possibly a catastrophic event, occurred ca. 1.4 Ga ago. This conclusion enables us to establish constraints on the timescale of asteroid disruption frequency, the validity of the crater chronology and the mean lifetime of small NEAs.

Erratum: Observation of the hyperfine spectrum of antihydrogen.

This corrects the article DOI: 10.1038/nature23446.

Antihydrogen accumulation for fundamental symmetry tests.

Antihydrogen, a positron bound to an antiproton, is the simplest anti-atom. Its structure and properties are expected to mirror those of the hydrogen atom. Prospects for precision comparisons of the two, as tests of fundamental symmetries, are driving a vibrant programme of research. In this regard, a limiting factor in most experiments is the availability of large numbers of cold ground state antihydrogen atoms. Here, we describe how an improved synthesis process results in a maximum rate of 10.5 ± 0.6 atoms trapped and detected per cycle, corresponding to more than an order of magnitude improvement over previous work. Additionally, we demonstrate how detailed control of electron, positron and antiproton plasmas enables repeated formation and trapping of antihydrogen atoms, with the simultaneous retention of atoms produced in previous cycles. We report a record of 54 detected annihilation events from a single release of the trapped anti-atoms accumulated from five consecutive cycles.Antihydrogen studies are important in testing the fundamental principles of physics but producing antihydrogen in large amounts is challenging. Here the authors demonstrate an efficient and high-precision method for trapping and stacking antihydrogen by using controlled plasma.

Observation of the hyperfine spectrum of antihydrogen.

The observation of hyperfine structure in atomic hydrogen by Rabi and co-workers and the measurement of the zero-field ground-state splitting at the level of seven parts in 1013 are important achievements of mid-twentieth-century physics. The work that led to these achievements also provided the first evidence for the anomalous magnetic moment of the electron, inspired Schwinger's relativistic theory of quantum electrodynamics and gave rise to the hydrogen maser, which is a critical component of modern navigation, geo-positioning and very-long-baseline interferometry systems. Research at the Antiproton Decelerator at CERN by the ALPHA collaboration extends these enquiries into the antimatter sector. Recently, tools have been developed that enable studies of the hyperfine structure of antihydrogen-the antimatter counterpart of hydrogen. The goal of such studies is to search for any differences that might exist between this archetypal pair of atoms, and thereby to test the fundamental principles on which quantum field theory is constructed. Magnetic trapping of antihydrogen atoms provides a means of studying them by combining electromagnetic interaction with detection techniques that are unique to antimatter. Here we report the results of a microwave spectroscopy experiment in which we probe the response of antihydrogen over a controlled range of frequencies. The data reveal clear and distinct signatures of two allowed transitions, from which we obtain a direct, magnetic-field-independent measurement of the hyperfine splitting. From a set of trials involving 194 detected atoms, we determine a splitting of 1,420.4 ± 0.5 megahertz, consistent with expectations for atomic hydrogen at the level of four parts in 104. This observation of the detailed behaviour of a quantum transition in an atom of antihydrogen exemplifies tests of fundamental symmetries such as charge-parity-time in antimatter, and the techniques developed here will enable more-precise such tests.

Observation of the 1S-2S transition in trapped antihydrogen.

The spectrum of the hydrogen atom has played a central part in fundamental physics over the past 200 years. Historical examples of its importance include the wavelength measurements of absorption lines in the solar spectrum by Fraunhofer, the identification of transition lines by Balmer, Lyman and others, the empirical description of allowed wavelengths by Rydberg, the quantum model of Bohr, the capability of quantum electrodynamics to precisely predict transition frequencies, and modern measurements of the 1S-2S transition by Hänsch to a precision of a few parts in 1015. Recent technological advances have allowed us to focus on antihydrogen-the antimatter equivalent of hydrogen. The Standard Model predicts that there should have been equal amounts of matter and antimatter in the primordial Universe after the Big Bang, but today's Universe is observed to consist almost entirely of ordinary matter. This motivates the study of antimatter, to see if there is a small asymmetry in the laws of physics that govern the two types of matter. In particular, the CPT (charge conjugation, parity reversal and time reversal) theorem, a cornerstone of the Standard Model, requires that hydrogen and antihydrogen have the same spectrum. Here we report the observation of the 1S-2S transition in magnetically trapped atoms of antihydrogen. We determine that the frequency of the transition, which is driven by two photons from a laser at 243 nanometres, is consistent with that expected for hydrogen in the same environment. This laser excitation of a quantum state of an atom of antimatter represents the most precise measurement performed on an anti-atom. Our result is consistent with CPT invariance at a relative precision of about 2 × 10-10.

An improved limit on the charge of antihydrogen from stochastic acceleration.

Antimatter continues to intrigue physicists because of its apparent absence in the observable Universe. Current theory requires that matter and antimatter appeared in equal quantities after the Big Bang, but the Standard Model of particle physics offers no quantitative explanation for the apparent disappearance of half the Universe. It has recently become possible to study trapped atoms of antihydrogen to search for possible, as yet unobserved, differences in the physical behaviour of matter and antimatter. Here we consider the charge neutrality of the antihydrogen atom. By applying stochastic acceleration to trapped antihydrogen atoms, we determine an experimental bound on the antihydrogen charge, Qe, of |Q| < 0.71 parts per billion (one standard deviation), in which e is the elementary charge. This bound is a factor of 20 less than that determined from the best previous measurement of the antihydrogen charge. The electrical charge of atoms and molecules of normal matter is known to be no greater than about 10(-21)e for a diverse range of species including H2, He and SF6. Charge-parity-time symmetry and quantum anomaly cancellation demand that the charge of antihydrogen be similarly small. Thus, our measurement constitutes an improved limit and a test of fundamental aspects of the Standard Model. If we assume charge superposition and use the best measured value of the antiproton charge, then we can place a new limit on the positron charge anomaly (the relative difference between the positron and elementary charge) of about one part per billion (one standard deviation), a 25-fold reduction compared to the current best measurement.

Three-year cardiovascular events and disease progress in patients with peripheral arterial disease: results from the Japan Medication Therapy for Peripheral Arterial Disease (J-METHOD).

AIM: To investigate the current status of peripheral arterial disease (PAD) drug treatment in Japan, and the effects of drug treatment, risk factors, and complications on disease progress and onset of cardiovascular events in PAD patients. METHODS: In this prospective observational cohort study, 557 PAD patients were followed up for 3 years, and the current status of PAD treatment, risk factors, and cardiovascular events were monitored. RESULTS: Three drugs, i.e., beraprost sodium, cilostazol, and aspirin, were most frequently used. The patients who had undergone vascular reconstruction of the lower limbs before enrollment showed significant improvement in ABI. Among the patients who had not undergone vascular reconstruction before enrollment, there was a significant improvement in ABI after treatment with beraprost. During the observation period, cardiovascular deaths occurred in 35 patients (6.3%), heart diseases in 63 (11.3%), brain diseases in 39 (7.0%), and events in the lower limbs in 94 (16.9%). The factors affecting the increase of the cardiovascular events were explored by multivariate analysis (Cox regression analysis). As a result, age (75 years or older), ischemic heart disease and increase in severity on the Fontaine classification were identified as significant factors for cardiovascular deaths, whereas kidney disorders and increase in severity on the Fontaine classification were identified for heart diseases, the number of oral drugs for treating PAD was identified for brain diseases, and age (younger than 75 years), dialysis, ABI (less than 0.7) and aspirin were identified for the events in the lower limbs. CONCLUSION: As a result of the three-year follow-up on the Japanese PAD cohort, the current status of PAD treatment, risk factors, and cardiovascular events could be identified.

Impact of superselective transarterial infusion therapy of high-dose cisplatin on maxillary cancer with orbital invasion.

BACKGROUND AND PURPOSE: We have been performing the superselective transarterial infusion of high-dose cisplatin for advanced maxillary cancer since 1998 and the local control rate, disease free survival rate, and organ preservation have improved markedly compared with our former therapy. This study evaluates the effectiveness of superselective transarterial infusion therapy by using high-dose cisplatin on maxillary cancer with orbital invasion. MATERIALS AND METHODS: We treated 23 patients with maxillary cancer by using superselective transarterial infusion therapy with high-dose cisplatin and concomitant radiation therapy for 10 years. Of all patients, 15 showed orbital invasion, with 11 of these tumors fed by both internal maxillary and ophthalmic arteries. In all patients, we performed superselective transarterial infusion therapy via the internal maxillary artery and/or the other feeding branches from the external carotid artery. After the operation, we determined whether a pCR had occurred by checking for the presence of viable cells. In addition, we calculated the overall survival rate, preservation rate of the eyeball, and disease-free survival rate. RESULTS: For all 23 patients, pCR and overall survival rates were 95.7% and 78.4%, respectively. To date, 2 of these patients died of lung metastasis without local recurrence. For the 15 patients with orbital invasion, the respective pCR and disease-free survival rates were 93.3% and 87.5%. Eyeballs were preserved in all patients, and local recurrence occurred in only 1 patient, at the inferior wall of the maxillary sinus (not in the orbit). CONCLUSIONS: Superselective transarterial infusion therapy with high-dose cisplatin remarkably improved the local control rate and disease-free survival rate of maxillary cancer. Even in patients with orbital invasion, a high local control rate was achieved, with preservation of the eyeball, through infusion only into branches of the external carotid artery.

Presence of quorum-sensing inhibitor-like compounds from bacteria isolated from the brown alga Colpomenia sinuosa.

AIMS: Several Gram-negative bacterial species use N-acyl homoserine lactone (AHL) molecules as quorum-sensing (QS) signals to regulate various biological functions. Similarly, various bacteria can stimulate, inhibit or inactivate QS signals in other bacteria by producing molecules called as quorum-sensing inhibitors (QSI). Our aim was to screen and identify the epibiotic bacteria associated with brown algae for their ability of producing QS-inhibiting activity. METHODS AND RESULTS: QSI screenings were conducted on several epibiotic bacteria isolated from a marine brown alga Colpomenia sinuosa, using Serratia rubidaea JCM 14263 as an indicator organism. Strain JCM 14263 controls the production of red pigment, prodigiosin by AHL QS. Out of 96 bacteria, which were isolated from the surface of the brown alga, 12% of strains showed the ability to produce QSI, which was observed from the pigmentation inhibition on Ser. rubidaea JCM 14263 without affecting its growth. Phylogenetic analysis using 16S rRNA gene sequencing method demonstrated bacterial isolates showing QS inhibition-producing bacteria belonging to the Bacillaceae (Firmicutes), Pseudomonadaceae (Proteobacteria), Pseudoalteromonadaceae (Proteobacteria) and Vibrionaceae (Proteobacteria). CONCLUSION: An appreciable percentage of bacteria isolated from the brown alga produced QSI-like compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: The screening method using Ser. rubidaea described in this report will facilitate the rapid identification of QSI-producing bacteria from marine environment. This study reveals new avenue for future environmental applications. This study also suggests that these algal epibiotic bacteria may play a role in the defensive mechanism for their host by producing QSI or QSI-like compounds to suppress the settlement of other competitive bacteria.

[Aortic dissection after aortic valve replacement with an aorto-left atrial fistula; report of a case].

Aortocameral fistula is a rare complication of aortic dissection. We herein report a case of aortic dissection after aortic valve replacement (AVR) complicated with a fistula to the left atrium. A 76-year-old man who had undergone AVR 1 year previously, was admitted to our hospital because of facial edema and chest discomfort. On auscultation, a continuous murmur was heard at the left lower sternal border. Computed tomography revealed dissecting aneurysm of the ascending aorta and a fistula to the left atrium was suspected. Transesophageal echocardiography showed the fistula between the false lumen of the aneurysm and the left atrium. Ascending aorta replacement and closure of the fistula was performed. There was dense adhesion between the aortic root and the roof of the left atrium. It seems that postoperative adhesion plays an important role in formation of aortocameral fistula.

[Full-thickness pleural biopsy using an Insulation-tipped Diathermic Knife in a patient with malignant pleural mesothelioma].

A 72-year-old woman was pointed out a right pleural effusion and thickening pleura on the chest computed tomography. The patient underwent semiflexible thoracoscopy under local anesthesia at the endoscopy room. The patient was placed in the lateral decubitus position, and flexible trocar was inserted with the single puncture technique. At the macroscopic findings, the parietal pleura were thickened prominently, and patchy plaques were occasionally recognized. A standard biopsy forceps hardly grasped pleura because of presence of scar, so we performed pleural biopsy using Insulation-tipped Diathermic (IT) knife. A subpleural injection of saline containing 0.5% lidokine and 0.005% epinephrine was performed for raising the affected parietal pleura with an injection needle. After a pin hole was made, the pleural lesion was incised in a circle by manipulating the IT knife, and the incised pleura were removed. Pathology revealed extensive fibrosis and epithelial mesothelioma by the specimen. This biopsy technique using IT knife through semiflexible thoracoscopy enabled to obtain a full-thickness pleura It is thought to be useful for the diagnosis of malignant pleural mesothelioma (MPM) in which standard forceps are difficult to grasp.

Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases: physiological and pharmacological significance of protein phosphatases.

Multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs) play pivotal roles in intracellular Ca2+ signaling pathways. There is growing evidence that CaMKs are involved in the pathogenic mechanisms underlying various human diseases. In this review, we begin by briefly summarizing our knowledge of the involvement of CaMKs in the pathogenesis of various diseases suggested to be caused by the dysfunction/dysregulation or aberrant expression of CaMKs. It is widely known that the activities of CaMKs are strictly regulated by protein phosphorylation/dephosphorylation of specific phosphorylation sites. Since phosphorylation status is balanced by protein kinases and protein phosphatases, the mechanism of dephosphorylation/deactivation of CaMKs, corresponding to their 'switching off', is extremely important, as is the mechanism of phosphorylation/activation corresponding to their 'switching on'. Therefore, we focus on the regulation of multifunctional CaMKs by protein phosphatases. We summarize the current understanding of negative regulation of CaMKs by protein phosphatases. We also discuss the biochemical properties and physiological significance of a protein phosphatase that we designated as Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP), and those of its homologue CaMKP-N. Pharmacological applications of CaMKP inhibitors are also discussed. These compounds may be useful not only for exploring the physiological functions of CaMKP/CaMKP-N, but also as novel chemotherapies for various diseases.

Evaluating efficacy of plasmapheresis for patients with pemphigus using desmoglein enzyme-linked immunosorbent assay.

BACKGROUND: Pemphigus is an autoimmune bullous disease caused by circulating IgG autoantibodies against cell-cell adhesion molecules between keratinocytes: desmoglein (Dsg) 3 and Dsg1. Plasmapheresis is often used to treat severe cases of pemphigus. Enzyme-linked immunosorbent assays (ELISAs) against recombinant Dsg3 and Dsg1 have recently become available, allowing us to quantify IgG autoantibodies against Dsg3 and Dsg1. OBJECTIVES: Using ELISA against recombinant Dsg3 and Dsg1, to evaluate the efficacy of plasmapheresis in pemphigus. METHODS: Sera obtained from 10 patients with pemphigus vulgaris and one with pemphigus foliaceus following a total of 16 cycles of centrifugal plasmapheresis and 12 effluents from the plasmapheresis were subjected to ELISA against Dsgs. The percentage of IgG autoantibodies removed was calculated using two different formulae: one used serum titres before and immediately after plasmapheresis and the other used the absolute amounts of IgG autoantibodies in the effluents. The percentage fall of anti-Dsg antibody level was also calculated using the serum titres 1 day after plasmapheresis. RESULTS: Using serum titres immediately after plasmapheresis, there was a mean fall per treatment in anti-Dsg 3 antibody level of 43.0% (n = 12) and in anti-Dsg1 antibody level of 48.4% (n = 7). By contrast, calculated from the effluents, on average one treatment removed only 14.6% of anti-Dsg3 antibodies (n = 12) and 16.4% of anti-Dsg1 antibodies (n = 7). This should reflect the correct percentage as it is based on the absolute amounts of IgG autoantibodies removed. Using serum titres 1 day after plasmapheresis, there was a mean fall per treatment in anti-Dsg 3 antibody level of 12.9% (n = 2) and in anti-Dsg1 antibody level of 8.4% (n = 4). The percentage of IgG autoantibodies removed 1 day after plasmapheresis was lower than that found to be removed immediately after plasmapheresis (n = 6). CONCLUSIONS: One centrifugal plasmapheresis procedure eliminates about 15% of the IgG autoantibodies from the whole body. The percentage fall of anti-Dsg IgG antibody level differed depending on when the serum samples were obtained after plasmapheresis. The change in the percentage fall of anti-Dsg antibody level within 1 day after plasmapheresis is thought to be attributable to the passive diffusion of the IgG autoantibodies from the extravascular space to the intravascular space. Therefore, removal of IgG autoantibodies calculated using serum titres only should be evaluated carefully considering the equilibration of the IgG autoantibodies between the different body spaces.

Effects of orally administered glycine on myofibrillar proteolysis and expression of proteolytic-related genes of skeletal muscle in chicks.

We examined the effects of orally administered glycine on myofibrillar proteolysis in food-deprived chicks. Food-deprived (24 h) chicks were orally administered 57, 113, and 225 mg glycine/100 g body weight and killed after 2 h. The plasma N(tau)-methylhistidine concentration, used as myofibrillar proteolysis, was decreased by glycine. We also examined the expression of proteolytic-related genes by real-time PCR of cDNA from chick skeletal muscles. The mRNA expression of atrogin-1/MAFbx, proteasome C2 subunit, m-calpain large subunit, and cathepsin B was decreased by glycine in a dose-dependent manner. The plasma corticosterone concentration was also decreased by glycine, but the plasma insulin concentration was unaffected. These results indicate that orally administered glycine suppresses myofibrillar proteolysis and expression of proteolytic-related genes of skeletal muscle by decreasing the plasma corticosterone concentration in chicks.

Generation of anti-tumour effector T cells from naïve T cells by stimulation with dendritic/tumour fusion cells.

Tumour-draining lymph node T cells are an excellent source of effector T cells that can be used in adoptive tumour immunotherapy because they have already been sensitized to tumour-associated antigens in vivo. However, such tumour-specific immune cells are not readily obtained from the host due to poor immunogenicity of tumours and reduced host immune responses. One obstacle in implementation of adoptive immunotherapy has been insufficient sensitization and expansion of tumour-specific effector cells. In this study, we aim to improve adoptive immunotherapy by generating anti-tumour effector T cells from naïve T lymphocytes. We attempted to achieve this by harnessing the advantages of dendritic cell (DC)-based anti-cancer vaccine strategies. Electrofusion was routinely employed to produce fusion cells with 30-40% efficiency by using the poorly immunogenic murine B16/F10 cell line, D5 cells, and DC generated from bone marrow cells. CD62L-positive T cells from spleens of naïve mice and the fusion cells were cocultured with a low concentration of IL-2. After 9 days of culture, the antigen-specific T cells were identified with an upregulation of CD25 and CD69 expression and a downregulation of CD62L expression. These cells secreted IFN-gamma upon stimulation with irradiated tumour cells. Moreover, when transferred into mice with 3-day established pulmonary metastases, these cells with coadministration of IL-2 exhibited anti-tumour efficacy. In contrast, naïve T cells cocultured with a mixture of unfused DC and irradiated tumour cells did not exhibit anti-tumour efficacy. Our strategy provides the basis for a new approach in adoptive T cell immunotherapy for cancer.

Suppression of myofibrillar proteolysis in chick skeletal muscles by alpha-ketoisocaproate.

We previously reported that L-leucine suppresses myofibrillar proteolysis in chick skeletal muscles. In the current study, we compared the effects of L- and D-enantiomers of leucine on myofibrillar proteolysis in skeletal muscle of chicks. We also assessed whether leucine itself or its metabolite, alpha-ketoisocaproate (alpha-KIC), mediates the effects of leucine. Food-deprived (24 h) chicks were orally administered 225 mg/100 g body weight L-leucine, D-leucine or alpha-KIC and were sacrificed after 2 h. L-Leucine administration had an obvious inhibitory effect on myofibrillar proteolysis (plasma N(tau)-methylhistidine concentration) in chicks while D-leucine and alpha-KIC were much more effective. We also examined the expression of the proteolytic-related genes (ubiquitin, proteasome, m-calpain and cathepsin B) by real-time PCR of cDNA in chick skeletal muscles. Ubiquitin mRNA expression was decreased by D-leucine and alpha-KIC but not L-leucine. Proteasome and m-calpain mRNA expressions as well as cathepsin B mRNA expression were likewise decreased by L-leucine, D-leucine and alpha-KIC. These results indicate that D-leucine and alpha-KIC suppress proteolytic-related genes, resulting in an decrease in myofibrillar proteolysis while L-leucine is much less effective in skeletal muscle of chicks, may be explain by conversion of D-leucine to alpha-KIC.

A key role for the subunit SUR2B in the preferential activation of vascular KATP channels by isoflurane.

BACKGROUND AND PURPOSE: It has been postulated that isoflurane, a volatile anaesthetic, produces vasodilatation through activation of ATP-sensitive K+ (KATP) channels. However, there is no direct evidence for the activation of vascular KATP channels by isoflurane. This study was conducted to examine the effect of isoflurane on vascular KATP channels and compare it with that on cardiac KATP channels. EXPERIMENTAL APPROACH: Effects of isoflurane on KATP channels were examined in aortic smooth muscle cells and cardiomyocytes of the mouse using patch clamp techniques. Effects of the anaesthetic on the KATP channels with different combinations of the inward rectifier pore subunits (Kir6.1 and Kir6.2) and sulphonylurea receptor subunits (SUR2A and SUR2B) reconstituted in a heterologous expression system were also examined. KEY RESULTS: Isoflurane increased the coronary flow in Langendorff-perfused mouse hearts in a concentration-dependent manner, which was abolished by 10 microM glibenclamide. In enzymically-dissociated aortic smooth muscle cells, isoflurane evoked a glibenclamide-sensitive current (i.e. KATP current). In isolated mouse ventricular cells, however, isoflurane failed to evoke the KATP current unless the KATP current was preactivated by the K+ channel opener pinacidil. Although isoflurane readily activated the Kir6.1/SUR2B channels (vascular type), the volatile anesthetic could not activate the Kir6.2/SUR2A channels (cardiac type) expressed in HEK293 cells. Isoflurane activated a glibenclamide-sensitive current in HEK293 cells expressing Kir6.2/SUR2B channels. CONCLUSION AND IMPLICATIONS: Isoflurane activates KATP channels in vascular smooth muscle cells and produces coronary vasodilation in mouse hearts. SUR2B may be important for the activation of vascular-type KATP channels by isoflurane.

Successful management of critical limb ischemia with intravenous sodium thiosulfate in a chronic hemodialysis patient.

Vascular calcification is common among hemodialysis (HD) patients and contributes to the development of peripheral arterial disease. A 57-year-old Japanese man who had been on HD for 30 years was referred to us for severe pain with multiple ulcers on his toes and fingers. He was an ex-smoker and had no diabetes mellitus. On admission, he had ulcers on his big toes bilaterally and right 2nd - 4th fingers. Peripheral pulses were strong and his ankle-brachial pressure index was above 1.3. Laboratory data were as follows: calcium 9.9 mg/dl, albumin 3.3 g/dl, phosphate 3.0 mg/dl, Ca x P product 30, and parathyroid hormone 98 pg/ml. He had a parathyroidectomy in 1998 and 1999. X-rays of his hands and legs showed diffuse subcutaneous arteriolar calcification. Angiography revealed no local stenotic lesions. Despite intensive therapies including hyperbaric oxygen therapy, painful gangrene developed on his right big toe and the pain was so intense that he could not go to sleep in a supine position. We infused intravenous sodium thiosulfate (20 g) 3 times weekly, based on previous reports. Within 4 - 5 days, he experienced rapid and dramatic symptom relief. The score of the visual analogue pain scale improved from 10/10 - 2/10. The signs of ischemia, measured by transcutaneous partial oxygen pressure and thermography, improved significantly. During the infusion of sodium thiosulfate, the patient complained of nausea, vomiting and hyperosmia. These adverse symptoms were resolved after discontinuation of the infusion. Pain relief was sustained and he could walk after 2 weeks of infusion. Our case supports the use of sodium thiosulfate as a novel therapeutic choice for critical limb ischemia with severe vascular calcification in chronic HD patients.

Prevention of onset of Parkinson's disease by in vivo gene transfer of human hepatocyte growth factor in rodent model: a model of gene therapy for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SNi). As neurotrophic factors support the survival and enhance the function of dopaminergic neurons, gene therapy using neurotrophic factors has become the center of interest. Thus, we focused on hepatocyte growth factor (HGF) as a neurotrophic and angiogenic growth factor. At 7 days before injection of 6-hydroxydopamine into the SNi, stereotaxic transfection of human HGF or lacZ plasmid was performed into the unilateral striatum of rats. Expression of human HGF in the injected sites could be detected in rats transfected with HGF plasmid DNA, using immunohistochemical staining. Consistently, human immunoreactive HGF protein could be detected at least up to 12 days after transfection. Interestingly, PD rats transfected with lacZ demonstrated amphetamine-induced rotational asymmetry. However, transfection of HGF plasmid DNA resulted in significant inhibition of abnormal rotation up to 24 weeks in a dose-dependent manner. Over 90% of dopaminergic neurons were lost in PD rats transfected with lacZ, whereas over 70% survived in rats transfected with HGF, as assessed by immunohistochemical staining. Overall, the present study demonstrated that overexpression of HGF prevented neuronal death in a PD rat model, providing a potential novel therapy for PD.

[Surgical technique of aortic valve replacement for small aortic annulus in elderly patients].

Recent reports have shown that aortic valve replacement in elderly patients over 65 years with atherosclerotic aortic stenosis and a small aortic annulus is possible by using a small sized bioprosthesis (Carpentier-Edwards pericardial valve). Here we present out surgical technique. Firstly, the native calcified aortic valve was removed completely to gain total exposure of the surrounding aortic root and sinus of Valsalva like Bentall procedure. Secondly, a small sized bioprosthesis was implanted with intermittent noneverting mattress 2-0 sutures with spaghetti and small polytetrafluoroethylene (PTFE) felt. Aortic annulus is the dilated by inserting Hegar dilator sizing from 25 to 27 mm. Therefore, aortic valve replacement for small aortic annulus in intra- or supra-annular position should be easily accomplished. Good surgical results and hemodynamic state were achieved in 25 consecutive cases using this technique.