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This study assessed the significance of measuring liver stiffness using virtual touch quantification before hepatectomy to predict posthepatectomy refractory ascites. A total of 267 patients with hepatocellular carcinoma who underwent hepatectomy were prospectively analyzed. Liver stiffness was defined as the median value of the virtual touch quantification (Vs; m/s) by acoustic radio-force-impulse-based virtual touch. A multivariate analysis showed that Vs and the aspartate aminotransferase-to-platelet ratio index were independent risk factors for postoperative refractory ascites (odds ratio = 3.27 and 3.08, respectively). The cutoff value for Vs was 1.52 m/s (sensitivity: 59.5%, specificity: 88.6%) as determined by the analysis of the receiver-operating characteristic curve, and the area under the receiver-operating characteristic curve was 0.79. The cutoff value for the aspartate aminotransferase-to-platelet ratio was 0.952 (sensitivity: 65.5%, specificity: 82.9%), and the area under the receiver-operating characteristic curve was 0.75. Vs is an independent risk factor for refractory ascites after hepatectomy. The measurement of liver stiffness by virtual touch quantification before hepatectomy can help estimate the risk of postoperative refractory ascites. Nonsurgical treatments should be considered for the management of patients who are at high risk for refractory ascites.

The Japanese guidelines for the treatment of gastric cancer recommend nivolumab as third-line chemotherapy for metastatic gastric adenocarcinoma. We report a case in which long-term control of metastatic gastric adenocarcinoma was achieved with nivolumab after pseudoprogression. A man in his late 70s with advanced HER2-negative gastric cancer and liver metastasis underwent total gastrectomy to control tumor bleeding. He then underwent chemotherapy with S-1 plus oxaliplatin, followed by S-1 alone. After metastases in the liver and para-aortic and hilar lymph nodes regrew, the patient received ramucirumab plus paclitaxel as second-line chemotherapy, followed by third-line therapy with nivolumab. After four cycles of nivolumab, these metastases showed progression;however, the treatment was continued because levels of CA19-9 were decreased, and performance status was good. After five more cycles of nivolumab, the liver metastasis shrank, and CA19-9 levels decreased;therefore, we confirmed pseudoprogression. The patient suffered no immune-related adverse events and survived for 50 months after gastrectomy with 34 cycles of nivolumab treatment. Thus, at the beginning of treatment with an immune checkpoint inhibitor, oncologists must consider the possibility of pseudoprogression in cases of tumor growth associated with decreasing tumor marker levels and good performance status.

Purpose We investigated whether daily consumption of Spirulina, an antioxidant generating cyanobacterial nutritional supplement, would suppress photostress-induced retinal damage and prevent vision loss in mice. Methods Six-week-old male BALB/cAJcl mice were allowed constant access to either a standard or Spirulina-supplemented diet (20% Spirulina) that included the antioxidants, β-carotene and zeaxanthin, and proteins for 4 weeks. Following dark adaptation, mice were exposed to 3000-lux white light for 1 hour and returned to their cages. Visual function was analyzed by electroretinogram, and retinal histology by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated, deoxyuridine triphosphate nick-end labeling (TUNEL) assay, and immunohistochemistry. Retinal expression of proteins, reactive oxygen species (ROS), and mRNAs were measured using immunoblot analysis, enzyme-linked immunosorbent assay (ELISA), 2',7'-dichlorofluorescein-diacetate, or ROS Brite 700 Dyes, and real-time reverse-transcription polymerase chain reaction, respectively. Results Light-induced visual function impairment was suppressed by constant Spirulina intake. Thinning of the photoreceptor layer and outer segments, photoreceptor cell death, decreased rhodopsin protein, and induction of glial fibrillary acidic protein were ameliorated in the Spirulina-intake group. Increased retinal ROS levels after light exposure were reduced by Spirulina supplementation. Light-induced superoxide dismutase 2 and heme oxygenase-1 mRNAs in the retina, and Nrf2 activation in the photoreceptor cells, were preserved with Spirulina supplementation, despite reduced ROS levels, suggesting two pathways for suppressing ROS, scavenging and induction of endogenous antioxidative enzymes. Light-induced MCP-1 retinal mRNA and proteins were also suppressed by Spirulina. Conclusions Spirulina ingestion protected retinal photoreceptors from photostress in the retina. Translational relevance Spirulina has potential as a nutrient supplement to prevent vision loss related to oxidative damage in the future.

Excessive exposure to light promotes degenerative and blinding retinal diseases such as age-related macular degeneration and retinitis pigmentosa. However, the underlying mechanisms of photo-induced retinal degeneration are not fully understood, and a generalizable preventive intervention has not been proposed. Bilberry extract is an antioxidant-rich supplement that ameliorates ocular symptoms. However, its effects on photo-stressed retinas have not been clarified. In this study, we examined the neuroprotective effects of bilberry extract against photo-stress in murine retinas. Light-induced visual function impairment recorded by scotopic and phototopic electroretinograms showing respective rod and cone photoreceptor function was attenuated by oral administration of bilberry extract through a stomach tube in Balb/c mice (750 mg/kg body weight). Bilberry extract also suppressed photo-induced apoptosis in the photoreceptor cell layer and shortening of the outer segments of rod and cone photoreceptors. Levels of photo-induced reactive oxygen species (ROS), oxidative and endoplasmic reticulum (ER) stress markers, as measured by real-time reverse transcriptase polymerase chain reaction, were reduced by bilberry extract treatment. Reduction of ROS by N-acetyl-L-cysteine, a well-known antioxidant also suppressed ER stress. Immunohistochemical analysis of activating transcription factor 4 expression showed the presence of ER stress in the retina, and at least in part, in Muller glial cells. The photo-induced disruption of tight junctions in the retinal pigment epithelium was also attenuated by bilberry extract, repressing an oxidative stress marker, although ER stress markers were not repressed. Our results suggest that bilberry extract attenuates photo-induced apoptosis and visual dysfunction most likely, and at least in part, through ROS reduction, and subsequent ER stress attenuation in the retina. This study can help understand the mechanisms of photo-stress and contribute to developing a new, potentially useful therapeutic approach using bilberry extract for preventing retinal photo-damage.

A simple and selective synthetic method of quinolines and indoles by the reaction of β-(2-nitrophenyl)-α,β-unsaturated ketones with carbon monoxide was developed. When β-(2-nitrophenyl)-α,β-unsaturated ketones were allowed to react with carbon monoxide and water in the presence of a stoichiometric amount of sulfur or a catalytic amount of selenium, the corresponding quinolines were produced in moderate-to-good yields. On the other hand, in the absence of water, the indoles were produced by the selenium-catalyzed reaction of the β-(2-nitrophenyl)-α,β-unsaturated ketones with carbon monoxide.

UNLABELLED Concanavalin A (Con A) treatment induces severe hepatitis in mice in a manner dependent on T cells, interferon (IFN)-gamma, and tumor necrosis factor (TNF). Treatment with the anticoagulant heparin protects against hepatitis, despite healthy production of IFN-γ and TNF. Here, we investigated molecular and cellular mechanisms for hypercoagulation-mediated hepatitis. After Con A challenge, liver of wild-type (WT) mice showed prompt induction of Ifnγ and Tnf, followed by messenger RNA expression of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), which initiate blood coagulation and inhibit clot lysis, respectively. Mice developed dense intrahepatic fibrin deposition and massive liver necrosis. In contrast, Ifnγ(-/-) mice and Ifnγ(-/-) Tnf(-/-) mice neither induced Pai1 or Tf nor developed hepatitis. In WT mice TF blockade with an anti-TF monoclonal antibody protected against Con A-induced hepatitis, whereas Pai1(-/-) mice were not protected. Both hepatic macrophages and sinusoidal endothelial cells (ECs) expressed Tf after Con A challenge. Macrophage-depleted WT mice reconstituted with hematopoietic cells, including macrophages deficient in signal transducer and activator of transcription-1 (STAT1) essential for IFN-γ signaling, exhibited substantial reduction of hepatic Tf and of liver injuries. This was also true for macrophage-depleted Stat1(-/-) mice reconstituted with WT macrophages. Exogenous IFN-γ and TNF rendered T-cell-null, Con A-resistant mice deficient in recombination-activating gene 2, highly susceptible to Con A-induced liver injury involving TF. CONCLUSIONS Collectively, these results strongly suggest that proinflammatory signals elicited by IFN-γ, TNF, and Con A in both hepatic macrophages and sinusoidal ECs are necessary and sufficient for the development of hypercoagulation-mediated hepatitis.

先端巨大症は下垂体腺腫より成長ホルモンが過剰分泌される比較的稀な疾患である．大腸や乳腺，前立腺などの悪性腫瘍を合併することが近年報告されている．症例は71歳の女性で，12年前に先端巨大症，下垂体腺腫に対してHardyの手術を施行された．術後通院は自己にて中断していた．排便時出血を認めたため，近医受診．痔疾を指摘され加療を受けたが，症状が続くため消化管を精査されたところ，S状結腸に1型腫瘍を認め，加療目的にて当科紹介となった．全身精査にてびまん性甲状腺腫大を認めるのみで転移所見はなかった．S状結腸切除を行い，良好に経過した．内分泌機能検査では成長ホルモンおよびIGF-1が高値であり，下垂体腺腫切除後，成長ホルモン過剰分泌抑制が不十分であった先端巨大症に合併したS状結腸癌と考えられた．ブリモクリプチンの投与を開始し，外来にて経過観察を行っている．

症例は55歳の男性で，平成16年5月に前医で肝S1の径2 cm大の肝細胞癌に対して肝動脈塞栓術を施行された．平成17年8月に右季肋部痛が出現し，腹部CTにて胆嚢内に血腫を認め，出血を伴った急性胆嚢炎の診断で胆摘術を施行された．胆嚢内に凝血塊の貯留を認め，粘膜は軽度の炎症所見を認めた．平成17年11月に背部痛，下血，黄疸が出現したため，精査を施行され，ERCPで胆道出血を認めた．腹部造影CTで尾状葉に径3 cmの境界不明瞭な腫瘍を認め，肝細胞癌再発が疑われ，当科紹介となった．肝細胞癌再発に対して手術を行うこととした．術中胆道鏡にてSpiegel葉胆管枝より連続性に左肝管へ進展する腫瘍栓を認めた．肝細胞癌の胆管浸潤と診断し，肝左葉および尾状葉全切除を施行した．肝細胞癌の胆管浸潤によって胆道出血を伴う症例の頻度は少ないが，肝細胞癌経過観察中の胆道出血の原因としての胆管浸潤も念頭におく必要がある．

Heterocyclic fluorophores 5,5-dibutyl-9-dibutylamino-5H-benzo[b]naphtho[1,2-d]furan-6-one (4) and 3,3-dibutyl-9-dibutylamino-3H-benzo[kl]xanthen-2-one (7) with dialkyl substituents linked in a nonconjugated fashion to the chromophore skeleton have been derived from quinol-type compounds 1 and 2, and their photophysical properties were investigated in solution and in the solid state. Fluorophores 4 and 7 exhibit strong fluorescence intensity in the solid-state relative to that of quinols 1 and 2; however, 1 and 4 or 2 and 7 exhibit similar fluorescence intensities in solution. To elucidate the dramatic effect of the dialkyl substituent on the solid-state fluorescence excitation and emission spectra, we performed semiempirical molecular orbital calculations (AM1 and INDO/S) and X-ray crystallographic analysis. On the basis of the results of the calculations and the X-ray crystal structures, the relation between the solid-state photophysical properties and the chemical and crystal structures of 4 and 7 were discussed. It was confirmed that introduction of bulky dialkyl substituents to the fluorophore skeleton can efficiently prevent the short π–π contact between the fluorophores in molecular aggregation states and cause a dramatic solid-state fluorescence enhancement. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Sulfur-assisted or Se-catalyzed reaction of the title α,β-unsaturated ketones (I) with CO and H2O affords quinolines (II) in moderate to good yield.

Novel heterocyclic quinol-type fluorophores (4 a-c) and (5 a-c) that contain substituents (R = Me, Bu, Ph) with nonconjugated linkages to the chromophore skeleton have been synthesized and their photophysical properties have been investigated in solution and in the solid state. Considerable differences in the absorption and fluorescence spectra were observed between the two states. Quinols 4 a-c and 5 a-c exhibited almost the same absorption and fluorescence spectra in solution; however, their solid-state fluorescence excitation and emission spectra in the crystalline state were quite different. We performed X-ray crystallographic analyses to elucidate the dramatic effect of the substituents of the nonconjugated linkage on the solid-state fluorescence excitation and emission spectra. The relationships between the solid-state photophysical properties and the chemical and crystal structures of 4 a-c and 5 a-c are discussed on the basis of the X-ray crystal structures.

We made considerations for microstructures on chromium film observed after femtosecond laser irradiation through an analytical study. Laser diffraction through an optical system with a rectangular aperture was analyzed for the estimation of intensity distribution at the focal point. Molecular dynamics (MD) simulation was also performed for the examination of laser ablation of metal by taking account of the electron–phonon relaxation. From results of diffraction calculation, it was shown that a typical surface pattern is significantly affected by laser intensity distribution. On the other hand, it may be estimated through the MD simulation that the porosity formation evolves by cumulative pulses with energy close to the ablation threshold and their surrounding grows to microcolumns with volume expansion.

A 78-year-old man was admitted to our hospital with right upper abdominal pain and fever. His general condition was poor. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the gallbladder. 18F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, a granulocyte-colony stimulating factor (G-CSF)–producing tumor was diagnosed (G-CSF 120 pg/mL). We performed cholecystectomy with central bisegmentectomy of the liver, lymph node dissection and right hemicolectomy. Histologically, the tumor was an adenosquamous cell carcinoma of the gallbladder. Immunohistochemical staining of the tumor cells was positive for G-CSF. Postoperatively, the general condition of the patient was improved. The fever subsided, the leukocyte count and serum G-CSF level normalized, and FDG-PET showed no uptake in the spine postoperatively. The patient showed no signs of recurrence at 27 months after undergoing surgery. FDG-PET is a useful method for diagnosing G-CSF–producing gallbladder carcinoma. Aggressive curative resection for G-CSF–producing gallbladder carcinoma may improve patients' general condition and prognosis.

Background Macular hole results from a tractional force at the vitreo-retinal interface which is developed by modification and subsequent degeneration of the posterior precortical vitreous and the internal limiting membrane (ILM). Meanwhile, the wet type of age-related macular degeneration (AMD) is caused by the submacular formation of choroidal neovascularization (CNV). Although exudative changes derived from CNV may cause epiretinal membrane (ERM) formation, which can also cause tractional force at the vitreo-retinal interface, there have been few reports of AMD-associated macular hole development in which the full thickness of the retinal tissue is completely torn by the tractional force. Moreover, intraoperative finding of macular hole associated with AMD with a possible involvement of subretinal lesion has not been described. Case presentation A 78-year-old man diagnosed with wet AMD with subretinal fluid and mild cataract received 8 treatments with intravitreal pegaptanib. After AMD remission, he developed a secondary macular hole in the same eye. He underwent a pars plana vitrectomy that successfully closed the macular hole. Intraoperatively, it was found that the patient’s vitreous was formed and that the ERM and ILM were adherent, suggesting the involvement of a tractional force at the vitreo-retinal interface due to an inflammatory reaction related to AMD and/or intravitreally injected chemical compounds, resulting in macular hole development. Changes in the condition of his AMD and the RPE were observed on a fluorescein angiogram (FA) and an indocyanine green angiogram (IA) that preceded macular hole development, suggesting that subretinal changes may also have been involved in the pathogenesis. Conclusion These clinical data, including the intraoperative findings and the temporal changes in the angiograms, suggest that an inflammatory reaction at the vitreo-retinal interface and subretinal lesion related to AMD contribute to the macular hole development in AMD patients treated with intravitreal injection.

Bi-doped Cu bicrystals with various [001] and [011] twist boundaries have been tensile tested at room temperature and 543K. The fracture stress and fracture strain depend strongly on the misorientation angle and tensile temperature. The difference in the degree of embrittlement among different grain boundaries is more significant at 543K. The fracture stress and fracture strain at 543K against misorientation curves display some clear peaks; θ=23°(Σ13A), 28°(Σ17A), 37°(Σ5) and 44°(Σ29A) for [001] boundaries and θ=50°(Σ11), 59°(Σ33C), 71°(Σ3) and 83°(Σ57B) for [011] boundaries. For the two types of grain boundary, a good correlation is found between the degree of embrittlement and grain-boundary energy. A higher-energy boundary is more brittle and fractures more easily with a lower tensile stress. The fracture stresses of [001] boundaries are greater than those of [011] boundaries.

The retina is composed of neural networks that are responsible for visual function, and vascular networks that support the tissue. Although vascular targeting therapies for retinal diseases have recently been developed, therapies directly targeting the neuronal component of these diseases have yet to be developed. Here, we review recent studies describing the pathological signaling that occurs within the neuronal cells of retinal disease models. The molecular changes caused by endogenous or exogenous factors in the retinal neural cells and the molecular events involved in neuroinflammation are illustrated. These underlying molecular mechanisms reveal promising targets for new therapeutic approaches for retinal neural disorders.

Bleeding control is a major concern during dental surgery. A novel photocoagulation method using an irradiating blue-violet light emitting diode (LED) was investigated.Some dental light-curving units can emit blue-violet wavelengths around 380-515 nm with two peaks (410 nm and 470 nm). These wavelengths can cover the maximum absorption spectra of hemoglobin (430 nm).Blue-violet LED 380-515 nm, 750 mW/cm(2), 10 sec (7.5 J/cm(2)) was used. Irradiation was performed for 10 sec or an additional 10 sec for 10 cases of tooth extraction at a distance of 1 cm from the socket. Bleeding was stopped by conventional roll pressure in another five cases as a control. Bleeding time for both procedures was measured. A Mann-Whitney U test was used for statistical analysis. In vitro transmission electron microscope (TEM) studies were performed to clarify the mechanism of hemostasis by blue-violet LED irradiation.Irradiation with the blue-violet LED yielded immediate hemostasis of the socket. Five cases showed coagulation within the first 10 sec, and another five cases required an additional 10 sec to fully control the bleeding. In contrast, the conventional method required 2-5 min (median 180 sec) to obtain hemostasis. The difference between the time required to stop the bleeding in the two methods was found to be statistically significant (p = 0.0014). A week later, the LED-irradiated sockets were healed uneventfully with epithelial covering. TEM showed the formation of a thin amorphous layer and an adjacent agglutination of platelets and other cellular elements under the layer at the interface of the irradiated blood.Blue-violet LED irradiation of bleeding sockets caused immediate clot formation and hemostasis. This procedure was safe and reliable and showed no adverse effects.

Magnetic translation symmetry on a finite periodic square lattice is investigated for an arbitrary uniform magnetic field in arbitrary dimensions. It can be used to classify eigenvectors of the Hamiltonian. The system can be converted to another system of half or lower dimensions. A higher dimensional generalization of Harper equation is obtained for tight-binding systems., Comment: 15 pages, 1 figure

Ablation characteristics of chromium thin film on quartz by femtosecond laser pulses were investigated. Experiments were performed by femtosecond double-pulse irradiation. Double pulses were obtained using a Michelson interferometer and irradiated to a target sample by a couple of afocal systems. Delay time was controlled by adjustment of optical path. Intensity ratio and delay time between first and second pulse are important factors in the double-pulse ablation. Surround of ablation area was affected by the second pulse after evolution of ablation plume induced by the first pulse. This affected area is remarkable, when first pulse has sufficient intensity and delay time is ade-quate for evolution of laser ablation plume. The condition in which the intensity of the first pulse is lower than that of the second pulse brings smaller size of ablation particles. Through molecular dynamics simulations, we found two types of laser ablation for double pulse irradiation. One is the normal ablation involving formation of the ablation front. The other is the fracturing ablation, whose mechanism is considered as follows: The first pulse irradiation with energy close to the ablation threshold yields porous structure in the vicinity of surface. When the second pulse is irradiated to activated area with porous structure, the fracturing ablation occurs. This simulation results were in good agreement with experimental results.Ablation characteristics of chromium thin film on quartz by femtosecond laser pulses were investigated. Experiments were performed by femtosecond double-pulse irradiation. Double pulses were obtained using a Michelson interferometer and irradiated to a target sample by a couple of afocal systems. Delay time was controlled by adjustment of optical path. Intensity ratio and delay time between first and second pulse are important factors in the double-pulse ablation. Surround of ablation area was affected by the second pulse after evolution of ablation plume induced by the first pulse. This affected area is remarkable, when first pulse has sufficient intensity and delay time is ade-quate for evolution of laser ablation plume. The condition in which the intensity of the first pulse is lower than that of the second pulse brings smaller size of ablation particles. Through molecular dynamics simulations, we found two types of laser ablation for double pulse irradiation. One is the normal ablation involving forma...

In recent years, the microfabrication technology has splendidly been developing in the various industrial applications. It is effective that laser wavelength and pulse duration in laser microfabrication are shorter on the viewpoints of enhancement of spatial resolution and improvements of microfabrication quality. In this paper, we report on the ablation characteristics of the chromium thin film on quartz substrate (what is called Cr binary photomask) by using femtosecond laser (130fs Ti:sapphire laser). The diffraction pattern of laser intense distribution is observed in image printing with the optical rectangular slit, as the result of effects of minimized thermal diffusion with femtosecond laser pulses. We have obtained the Cr ablation without substrate damage with sufficiently wider ablation laser power range for multiple laser pulse irradiation, though ablation of the large band gap materials like quartz is easily caused due to the multi-photon absorption process in femtosecond laser irradiation. Further we indicated that ablation region does not depend on the diffraction limit with the femtosecond laser pulses.

It is generally known that femtosecond laser processing has distinct characteristics such as slight heat affected zone and sharp edge. In the present study, we carried out femtosecond laser irradiation to chromium binary photomasks in air with a rectangular aperture. Some types of surface microstructure (ripples, columns, etc.) were observed in the laser-irradiated area. Microcolumns protruding above the original surface were formed after repetitive irradiation of pulses with energy close to the ablation threshold. In order to investigate the mechanism of microstructure formation, we adopted analytical approach. Laser diffraction through an optical system with a rectangular aperture was analyzed for the estimation of intensity distribution at the focal point. Molecular dynamics (MD) simulation was also conducted for the examination of laser ablation of metal by considering the electron-phonon relaxation. As a result, it was shown that porosity is formed in the vicinity of surface. This porosity deformation is caused by the insufficient energy to remove the material from the surface. It was estimated through the MD simulation that the porosity formation proceeds by repetitive irradiation of pulses with energy close to the ablation threshold and their surrounding grows to microcolumns. The microstructure formation is significantly influenced by irradiation condition such as laser energy and intensity distribution.It is generally known that femtosecond laser processing has distinct characteristics such as slight heat affected zone and sharp edge. In the present study, we carried out femtosecond laser irradiation to chromium binary photomasks in air with a rectangular aperture. Some types of surface microstructure (ripples, columns, etc.) were observed in the laser-irradiated area. Microcolumns protruding above the original surface were formed after repetitive irradiation of pulses with energy close to the ablation threshold. In order to investigate the mechanism of microstructure formation, we adopted analytical approach. Laser diffraction through an optical system with a rectangular aperture was analyzed for the estimation of intensity distribution at the focal point. Molecular dynamics (MD) simulation was also conducted for the examination of laser ablation of metal by considering the electron-phonon relaxation. As a result, it was shown that porosity is formed in the vicinity of surface. This porosity deformatio...

RNase HI from the hyperthermophile Sulfolobus tokodaii (Sto-RNase HI) is stabilized by its C-terminal residues. In this work, the stabilization effect of the Sto-RNase HI C-terminal residues was investigated in detail by thermodynamic measurements of the stability of variants lacking the disulfide bond (C58/145A), or the six C-terminal residues (ΔC6) and by structural analysis of ΔC6. The results showed that the C-terminal does not affect overall structure and stabilization is caused by local interactions of the C-terminal, suggesting that the C-terminal residues could be used as a “stabilization tag.” The Sto-RNase HI C-terminal residues (-IGCIILT) were introduced as a tag on three proteins. Each chimeric protein was more stable than its wild-type protein. These results suggested the possibility of a simple stabilization technique using a stabilization tag such as Sto-RNase HI C-terminal residues.

Background The unfolding speed of some hyperthermophilic proteins is dramatically lower than that of their mesostable homologs. Ribonuclease HII from the hyperthermophilic archaeon Thermococcus kodakaraensis (Tk-RNase HII) is stabilized by its remarkably slow unfolding rate, whereas RNase HI from the thermophilic bacterium Thermus thermophilus (Tt-RNase HI) unfolds rapidly, comparable with to that of RNase HI from Escherichia coli (Ec-RNase HI). Results To clarify whether the difference in the unfolding rate is due to differences in the types of RNase H or differences in proteins from archaea and bacteria, we examined the equilibrium stability and unfolding reaction of RNases HII from the hyperthermophilic bacteria Thermotoga maritima (Tm-RNase HII) and Aquifex aeolicus (Aa-RNase HII) and RNase HI from the hyperthermophilic archaeon Sulfolobus tokodaii (Sto-RNase HI). These proteins from hyperthermophiles are more stable than Ec-RNase HI over all the temperature ranges examined. The observed unfolding speeds of all hyperstable proteins at the different denaturant concentrations studied are much lower than those of Ec-RNase HI, which is in accordance with the familiar slow unfolding of hyperstable proteins. However, the unfolding rate constants of these RNases H in water are dispersed, and the unfolding rate constant of thermophilic archaeal proteins is lower than that of thermophilic bacterial proteins. Conclusions These results suggest that the nature of slow unfolding of thermophilic proteins is determined by the evolutionary history of the organisms involved. The unfolding rate constants in water are related to the amount of buried hydrophobic residues in the tertiary structure.