Number of computed tomography scanners and regional disparities based on population and medical resources in Japan.

This study aimed to discover the associations between the number of computed tomography (CT) scanners and the population, as well as number of medical resources to identify regional disparities in Japan. The number of CT scanners was tabulated for each detector row of CT scanners for hospitals and clinics in each prefecture. The number of CT scanners, patients, medical doctors, radiological technologists, facilities, and beds per 100,000 population was compared. Additionally, the number of hospitals with ≥ 200 beds and multidetector-row CT scanners with ≥ 64 rows were tabulated, and their ratios were calculated. Medical institutions in Japan have installed 14,595 scanners. CT scanners per 100,000 population were the highest in Kochi Prefecture, although the number of CT scanners in hospitals was the highest in Tokyo Prefecture. Multivariate analysis revealed the number of radiological technologists (ß coefficient: 0.49; P = 0.03), facilities (ß coefficient: 0.12; P < 0.01) and beds (ß coefficient: 0.46; P < 0.01) as independent factors for the number of CT scanners. Prefectures with a high proportion of hospitals with ≥ 200 beds also had a relatively high proportion of CT scanners with ≥ 64 rows (P < 0.01). Our survey revealed an association between regional disparities in the number of CT scanners in Japan, the population, and number of medical resources. A positive correlation was found between hospital size and number of CT scanners with ≥ 64 rows.

Validation of the influence of CT slice thickness on the quantitative accuracy and image quality of single photon emission computed tomography.

OBJECTIVES: Computed tomography (CT) images are used for precise anatomical location of lesions and for accurate attenuation correction in single-photon emission computed tomography (SPECT) image reconstruction in SPECT/CT examination. The aim of this study was to verify the effects of varying CT collimation width and slice thickness on CT images and on CT attenuation corrected SPECT images. METHODS: We acquired SPECT/CT images of a micro-coin phantom and the National Electrical Manufacturers Association body phantom filled with 99mTc-pertechnetate while varying the abovementioned CT parameters. The full width at half maximum of the slice sensitivity profile, the standard deviation of CT image background noise, and the radiation dose from CT scans were evaluated. Subsequently, the percentage contrast, background variability, and absolute recovery coefficient of the SPECT image were measured. Furthermore, we retrospectively reviewed the clinical bone SPECT images of 23 patients, and statistical testing of differences was performed. RESULTS: As the collimation width and reconstruction slice thickness of the CT image increased, z-axis resolution deteriorated, and background noise decreased. In addition, CT radiation dose decreased with increasing collimation width. Meanwhile, SPECT image quality and quantitative accuracy were unchanged with varying CT collimation width and slice thickness. There were no notable variations in clinical SPECT images and no statistically significant differences. CONCLUSION: When high-resolution CT slices on the z-axis are not required for clinical diagnosis, increasing collimation width or slice thickness can reduce the radiation dose and image noise with no influence on the quality of SPECT images .

[A Questionnaire Survey on the Levels of Perception and Implementation on Diagnostic Reference Levels in Japan (Japan DRLs 2015)].

In June 2015, Japanese diagnostic reference levels (Japan DRLs 2015) was released by Japan Network for Research and Information on Medical Exposures (J-RIME). After six months the release of Japan DRLs 2015, we have conducted a questionnaire and received 222 responses from hospital staff regarding their perception level, and implementation on Japan DRLs 2015 at their facilities. 131 people (59.0%) were familiar with Japan DRLs 2015, of which 56 people (29.2%) were not currently implementation of them. A total of 66 people (30.1%) understood how to implement Japan DRLs 2015. There were 35 people (18.2%) who heard of diagnostic reference levels (DRLs) for the first time through this survey. Those are the levels of perception and implementation on Japan DRLs 2015 became clear. It is necessary to compare the dose levels used at each facility with Japan DRLs 2015 to optimize patient protection during medical exposure. It is essential to continue to grow the medical community's understanding of DRLs with the expanded perception and implementation of this survey as an opinion poll across Japan.

[A Case of Repeat Liver Resection after Laparoscopic Resection of a Synchronous Liver Metastasis of Colon Cancer].

A 44-year-old woman with subileus was diagnosed with advanced sigmoid colon cancer with a synchronous liver metasta- sis (segmanet 5/8). Laparoscopic anterior resection was performed, and histological diagnosis was sigmoid colon cancer, 55×40 mm, type 2, tub2>por2, pT3, ly2, v2, pN1, M1a, Stage Ⅳ (Japanese Classification of Colorectal Carcinoma, Eighth edition). Four courses of neoadjuvant chemotherapy (FOLFIRI plus panitumumab) shrank the liver metastasis. Laparoscopic partial liver resection was performed for 285 minutes, with 350 g of blood loss. The patient was discharged 9 days after the operation. Two courses of oral adjuvant chemotherapy (S-1) was performed but discontinued owing to side effects. Seven months after the surgery, computed tomography revealed 2 small liver metastasis (segment 8). Although the sizes were 35 and 5 mm, respectively, the larger mass was closed to the middle and right hepatic vein. Therefore, open hepatectomy was performed for 285 minutes, with 525 g of blood loss. The patient was discharged 9 days after the operation without complication. The patient had no recurrence for 1 year after the last surgery.

Interaction of peptide-bound beads with lipopolysaccharide and lipoproteins.

We previously reported the generation of lipopolysaccharide (LPS)-binding peptides by phage display and chemical modification. Among them, a dodecapeptide designated Li5-025 (K'YSSSISSIRAC'; K' and C' denote d-lysine and d-cysteine, respectively) showed a high binding affinity for LPS and was resistant to protease digestion (Suzuki et al., 2010). In the current study, Li5-025-bound silica beads, hereafter referred to as P-beads, were generated and found to be devoid of LPS-neutralizing activity. Thus, LPS bound to the P-beads could be directly used in the Limulus amebocyte lysate (LAL) assay. P-beads bound LPS dissolved in solutions of ethanol, pH4, pH10, and 0.5M NaCl and LPS bound to the P-beads was quantitatively assayed. The sensitivity of this assay was observed to be approximately 0.1pg/mL LPS. P-beads bound LPS dissolved in antithrombin III (AT III) solution which is a strong inhibitor of activated factors C and B as well as the clotting enzyme in the LAL assay; the inhibitory effect of AT III was completely reversed upon washing the P-beads with 25% acetonitrile. This was employed as the first step for the detection of free LPS in plasma using the LAL assay. LPS added to human plasma at 0°C followed by application to the P-beads and subsequent washing with 25% acetonitrile resulted in low LPS activity as detected by the LAL assay. However, further washing of the P-beads with 0.1% Triton X100 in 25% acetonitrile resulted in high LPS activity. This is the first instance of quantitative detection of free LPS in plasma using the LAL assay, and the sensitivity of this method was observed to be 1pg/mL of LPS. The proteins eluted in the 0.1% Triton X-100 wash were analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Two protein bands of 28kDa and 18kDa were predominantly observed. Mass spectrometry analysis revealed that the 28kDa and 18kDa bands corresponded to apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), respectively. ApoA-I and apoA-II are components of high density lipoprotein (HDL). Thus, it is likely that the P-beads-bound LPS was sequestered by HDL, resulting in neutralization of its toxicity. This study showed that by using P-beads, free LPS in plasma can be quantitatively measured by the LAL assay at a concentration of 1pg/mL.

Involvement of the distal Arg residue in Cl⁻ binding of midge larval haemoglobin.

Monomeric haemoglobin component V (Hb V) from the larva of the midge Propsilocerus akamusi shows high Cl⁻ affinity under high salt concentrations at acidic pH. In order to understand the structural changes that depend on Cl⁻ binding, crystal structures of Hb V were determined under acidic high-salt conditions and the structural changes arising from different haem-bound ligands were simulated. Crystal structures of Hb V under acidic high-salt conditions indicated that the side chain of ArgE10 on the distal face of the haem contributes to stabilizing haem-bound Cl⁻. The conformation of the Arg side chain in the Cl⁻-bound form was almost identical to that in ligated Hb V at neutral pH but not to that in met Hb V under acidic salt-free conditions. Furthermore, preliminary molecular-dynamics simulations also indicated that the swinging of the Arg side chain into the haem pocket depends on Cl⁻ ligation. This result suggests that, like pH change, Cl⁻ binding affects the location of the distal Arg residue. Owing to the increased positive electrostatic potential observed in the haem pocket at acidic pH, it was concluded that electrostatic changes caused by pH change and anionic ligand binding may affect the behaviour of the polar Arg residue.

Effect of elevated left ventricular diastolic filling pressure on the frequency of left atrial appendage thrombus in patients with nonvalvular atrial fibrillation.

We investigated the relation between left ventricular diastolic dysfunction and left atrial appendage (LAA) thrombus in patients with atrial fibrillation (AF). We performed transesophageal echocardiography to examine LAA thrombus or spontaneous echo contrast (SEC) and to measure LAA emptying flow velocity in consecutive 376 patients with AF. We estimated diastolic filling pressure as the ratio of early transmitral flow velocity (E) to mitral annular velocity (e') on transthoracic echocardiogram. E/e' ratio in 28 patients (7.4%) with LAA thrombi was higher than that in patients without thrombus (18.3 ± 9.3 vs 11.4 ± 5.9, p <0.0001). The fourth quartile of E/e' (>13.6) consisted of 19 patients with thrombi and had a higher prevalence of thrombi than the others (p <0.0001). Multivariate regression analysis selected E/e' ≥13 as an independent predictor of LAA thrombus with an odds ratio of 3.50 (1.22 to 10.61) in addition to LA dimension and ejection fraction. Increased quartile of E/e' was negatively associated with LAA flow velocity and positively with rate of SEC. In conclusion, increased diastolic filling pressure is associated with a higher rate of LAA thrombus in AF, partly through blood stasis or impaired LAA function.

Impact of concomitant diabetes and chronic kidney disease on preload-induced changes in left ventricular diastolic filling in hypertensive patients.

OBJECTIVES: Concomitant diabetes and/or chronic kidney disease (CKD) in hypertensive patients may portend additive deleterious effects on active left ventricular relaxation. We investigated the effect of a passive leg lifting (PLL) maneuver, a means of increasing preload, on left ventricular filling to assess the relationship of concomitant diabetes mellitus (DM) and/or CKD with diastolic function in hypertensive patients. METHODS: A total of 155 asymptomatic essential hypertensive patients underwent Doppler echocardiography to compare the echocardiographic indices at baseline and during PLL. In 51 patients, the effect of physiological saline infusion was also examined. RESULTS: The changes in echocardiographic indices, including deceleration time of early diastolic filling (EDT) and the ratio of transmitral early left ventricular filling velocity to early diastolic Doppler tissue imaging of the mitral annulus (E/E') by saline infusion showed a good correlation with those induced by PLL (Bland-Altman plot and linear regression). We next divided the total participants into four groups according to the presence/absence of diabetes and/or CKD [DM(-)/CKD(-); n = 48, DM(+)/CKD(-); n = 25, DM(-)/CKD(+); n = 43, and DM(+)/CKD(+); n = 39)] and found that the changes in EDT (F = 15.92, P < 0.01) as well as those in E/E' (F = 8.87, P < 0.01) were significantly different among the subgroups. Multiple logistic regression analysis revealed that these complications were independent predictors of EDT less than 150 ms [DM, odds ratio (OR): 2.82; CKD, OR: 2.18, P < 0.05, respectively] as well as E/E' ratio at least 15.0 during PLL (DM, OR: 4.78; CKD, OR: 3.32, P < 0.05, respectively). CONCLUSION: This simple preloading test unmasks latent progression of left ventricular dysfunction in essential hypertension; that is, these complications potentially cause deterioration of left ventricular compliance and preload reserve even in the early stages of diastolic dysfunction.

Molecular design of LPS-binding peptides.

Lipopolysaccharide (LPS), a major constituent of the outer membrane of Gram-negative bacteria, is highly toxic and can cause sepsis or septic shock. Therefore, detection of LPS and the ability to neutralize its toxicity is important. We previously obtained a strong LPS-binding peptide, Li5-001, using the phage display method (Matsumoto et al., 2010. J. Microbiol. Methods. 82, 54-58). We modified the sequence the amino acid sequence of this peptide (KNYSSSISSIHAC), by replacing and deleting amino acids to obtain higher LPS-binding affinity and greater resistance to protease digestion. Consequently we obtained a dodecapeptide, Li5-025 (K'YSSSISSIRAC', K' and C' are D-forms of K and C, respectively) which showed a high affinity for LPS, approximately 1000 folds higher affinity than Li5-001 and Kd value of 0.01 nM. By replacing both N- and C-terminal amino acids from L-type to D-type, the peptide was rendered resistant to protease digestion without altering its overall binding capacity.

Automated assessment of myocardial viability after acute myocardial infarction by global longitudinal peak strain on low-dose dobutamine stress echocardiography.

BACKGROUND: Low-dose dobutamine stress echocardiography (DSE) assesses myocardial viability at the early stage of acute myocardial infarction (AMI), but its assessment is subjective and variable. Automated function image (AFI) determines global longitudinal peak strain (GLPS) based on tissue tracking technique. The ability of GLPS obtained by AFI during dobutamine stress to assess myocardial viability after AMI was investigated. METHODS AND RESULTS: Low-dose DSE at day 3 in 23 consecutive patients with AMI was performed using Vivid 7 (GE Healthcare). Segmental longitudinal peak strain with AFI and obtained GLPS was analyzed. Wall motion score index (WMSI) by echocardiography 1 month later was determined. In 18 patients, left ventriculography was also performed at 3.2±1.5 months later to obtain left ventricular ejection fraction (LVEF) and regional wall motion (RWM, SD/chord). GLPS was improved during dobutamine infusion at 10 µg · kg(-1) · min(-1) (-12.9 ± 3.5% to -15.2 ± 3.6%, P=0.0004). GLPS during dobutamine stress showed good correlations with follow-up WMSI (R=0.47, P=0.02), with peak CK-MB (R = 0.52, P=0.01), with RWM (R = -0.48, P=0.04), and with LVEF (R = -0.54, P=0.02), whereas GLPS at baseline showed no correlations with them. Averaged segmental peak strain at baseline and during stress were correlated with follow-up WMSI (R = 0.50 and 0.43, respectively), but not with LVEF. CONCLUSIONS: GLPS during dobutamine stress determined by AFI is a promising, objective index to assess myocardial viability on the early stage of AMI.

Lipopolysaccaride-binding peptides obtained by phage display method.

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria. It has strong toxicity and might cause sepsis or septic shock. Thus early detection of LPS and neutralization of LPS toxicity are required. We obtained several new LPS-binding peptides using a phage display method. We synthesized 3 of these peptides and analyzed their binding affinity and capacity to LPS. One of these peptides, named Li5-001, showed high binding affinity to LPS and lipid A; the K(d) values were 10 and 1 nM, respectively. Li5-001 showed a high binding capacity to LPS, and was estimated to bind 130 ng LPS/mg, which is higher than that of polymyxin B (80 ng LPS/mg); however, its LPS-neutralizing activity was low. Li5-001 coupled with beads will be useful for eliminating endotoxin contamination from pharmaceuticals. Its low LPS-neutralizing activity allows to be used in the Limulus amebocyte lysate test without eluting LPS from the Li5-001 coupled beads.

Application of computerised correction method for optical distortion of two-dimensional facial image in superimposition between three-dimensional and two-dimensional facial images.

The applicability of computerised correction of optical distortion to two-dimensional (2D)/three-dimensional (3D) facial image superimposition was investigated. Two-dimensional (2D) facial images of 10 male volunteers were taken with a commercially available closed circuit device (CCD) camera (reference camera) at four areas of the lens field: the centre, top, upper right and right. Correction was made by computer by calculating differences vis-à-vis the co-ordinates of dots on a test chart. Discrepancies in facial outlines between the 3D and 2D images decreased following correction in all lens fields and were below the threshold for true positive. The correction method was also tested using an actual surveillance camera and video recorder installed in a bank. The method was found to be effective for the correction of facial images, especially those taken in the top and right lens fields. Since the total error (observed error) remaining after correction appeared close to the random error (real error), systematic error was thought to be minimised by correction. Therefore, the present method was thought to display high fidelity, and could be useful for supplementary examination of conventional superimposition.

pH-dependent structural changes in haemoglobin component V from the midge larva Propsilocerus akamusi (Orthocladiinae, Diptera).

Haemoglobin component V (Hb V) from the midge larva Propsilocerus akamusi exhibits oxygen affinity despite the replacement of HisE7 and a pH-dependence of its functional properties. In order to understand the contribution of the distal residue to the ligand-binding properties and the pH-dependent structural changes in this insect Hb, the crystal structure of Hb V was determined under five different pH conditions. Structural comparisons of these Hb structures indicated that at neutral pH ArgE10 contributes to the stabilization of the haem-bound ligand molecule as a functional substitute for the nonpolar E7 residue. However, ArgE10 does not contribute to stabilization at acidic and alkaline pH because of the swinging movement of the Arg side chain under these conditions. This pH-dependent behaviour of Arg results in significant differences in the hydrogen-bond network on the distal side of the haem in the Hb V structures at different pH values. Furthermore, the change in pH results in a partial movement of the F helix, considering that coupled movements of ArgE10 and the F helix determine the haem location at each pH. These results suggested that Hb V retains its functional properties by adapting to the structural changes caused by amino-acid replacements.

Macrophage inflammatory protein-1beta induced cell adhesion with increased intracellular reactive oxygen species.

UNLABELLED: To investigate the role of macrophage inflammatory protein-1 beta (MIP-1beta) in the development of atherosclerosis, we designed an in vitro study to elucidate the mechanisms of monocyte-endothelium adhesion via intracellular reactive oxygen species (ROS). Angiotensin II (AngII) was used as a positive control. Furthermore, we examined the efficacy of MIP-1beta as a predictor of stroke and cardiovascular events in hypertensive patients. MIP-1beta or AngII stimulation significantly increased ROS production and adhesion of THP-1 cells to inflamed human umbilical vein endothelial cells. Cell adhesion and ROS production were inhibited in stimulated THP-1 cells by: inhibition of ROS signaling with N-acetylcysteine, diphenyleneiodonium, or PEG-Catalase; inhibition of PI3Kgamma with siRNA or LY294002; and by Rac1 siRNA. The MIP-1 beta or AngII stimulation did not increase surface expression of integrins, very late antigen 4 (VLA-4) and lymphocyte function-associated antigen 1 (LFA-1), but cell adhesion was reduced by using an antiVLA-4 or an antiLFA-1 antibody. Moreover, cell adhesion and ROS production stimulated with MIP-1beta or AngII were completely inhibited by fluvastatin. In our clinical study, patients with the highest quartile of MIP-1beta showed a higher risk of stroke and cardiovascular events by a Cox proportional-hazards model. In conclusion, MIP-1beta directly induced cell adhesion to endothelial cells through oxidative stress via PI3k-Rac1 cascades. Serum MIP-1beta level might be a useful predictor for cerebro-cardiovascular events in hypertensive patients. CONDENSED ABSTRACT: We designed an in vitro investigation to examine the role of MIP-1beta on the development of atherosclerosis, including cell adhesion involving CAMs and ROS production, compared with angiotensin II. Furthermore, we investigated the prognostic impact of MIP-1beta on stroke and cardiovascular events in hypertensive patients in a small cohort study.

Comparison of arterial functional evaluations as a predictor of cardiovascular events in hypertensive patients: the Non-Invasive Atherosclerotic Evaluation in Hypertension (NOAH) study.

Increased arterial stiffness and impaired vasodilator response have been associated with cardiovascular events in high-risk patients. However, whether arterial changes predict the occurrence of hypertensive complications is still unclear. Therefore, we designed a hospital-based cohort study to examine the prognostic impact of arterial functional changes on stroke and cardiovascular diseases in hypertensive patients. The study employed 676 patients with essential hypertension. At baseline, we evaluated second-derived photoplethysmography, carotid-femoral pulse wave velocity (PWV), and forearm reactive hyperemia. We classified subjects into quartile groups according to the baseline measurements of these evaluations and assessed the ability of each measure to predict stroke and cardiovascular diseases (CVD). During a mean follow-up period of 57 months, 52 strokes, 40 CVD, and 22 deaths were recorded. Kaplan-Meier analysis revealed that patients in the highest quartile of PWV showed a higher frequency of stroke and CVD (p<0.0001) and total mortality (p=0.0016), and those in the highest quartile of reactive hyperemia showed a lower frequency of stroke and CVD (p=0.0415). A Cox hazard model identified that classification in the highest quartile of PWV (relative risk=2.717) and reactive hyperemia (0.416) were predictive of stroke and CVD after adjustment for other risk factors. In subjects who did not experience stroke or CVD before the study period (n=558), only PWV was related with the occurrence of stroke and CVD based on the Cox hazard model. In conclusion, increased aortic stiffness evaluated by PWV is more prognostic of cardiovascular events in hypertensive patients than several non-invasive atherosclerotic evaluations.

Characterization of the glutamyl endopeptidase from Staphylococcus aureus expressed in Escherichia coli.

V8 protease, a member of the glutamyl endopeptidase I family, of Staphylococcus aureus V8 strain (GluV8) is widely used for proteome analysis because of its unique substrate specificity and resistance to detergents. In this study, an Escherichia coli expression system for GluV8, as well as its homologue from Staphylococcus epidermidis (GluSE), was developed, and the roles of the prosegments and two specific amino acid residues, Val69 and Ser237, were investigated. C-terminal His(6)-tagged proGluSE was successfully expressed from the full-length sequence as a soluble form. By contrast, GluV8 was poorly expressed by the system as a result of autodegradation; however, it was efficiently obtained by swapping its preprosegment with that of GluSE, or by the substitution of four residues in the GluV8 prosequence with those of GluSE. The purified proGluV8 was converted to the mature form in vitro by thermolysin treatment. The prosegment was essential for the suppression of proteolytic activity, as well as for the correct folding of GluV8, indicating its role as an intramolecular chaperone. Furthermore, the four amino acid residues at the C-terminus of the prosegment were sufficient for both of these roles. In vitro mutagenesis revealed that Ser237 was essential for proteolytic activity, and that Val69 was indispensable for the precise cleavage by thermolysin and was involved in the proteolytic reaction itself. This is the first study to express quantitatively GluV8 in E. coli, and to demonstrate explicitly the intramolecular chaperone activity of the prosegment of glutamyl endopeptidase I.

Renal-protective effect of T-and L-type calcium channel blockers in hypertensive patients: an Amlodipine-to-Benidipine Changeover (ABC) study.

Both strict blood pressure control and efferent artery dilatation are critical in reducing proteinuria, which in turn helps to regulate blood pressure. Benidipine, an L- and T-type calcium channel blocker, has the potential for increased effectiveness compared with L-type-dominant calcium channel blockers such as amlodipine. Therefore, we evaluated blood pressure and proteinuria after changeover from amlodipine to benidipine in poorly controlled hypertensive patients. Fifty-eight hypertensive outpatients undergoing amlodipine treatment and unable to achieve optimal blood pressure as determined by Japanese Society of Hypertension Guidelines for the Management of Hypertention (JSH 2004) were changed over to benidipine treatment. We measured blood pressure and pulse rate and assessed urinary protein excretion before and after changeover. Systolic and diastolic blood pressure dropped from 151/90 mmHg to 140/81 mmHg (p<0.0001). Mean blood pressure (p<0.0001) and pulse pressure (p=0.0069) were also reduced, but pulse rate increased from 75 bpm to 78 bpm (p=0.0047). Urinary protein excretion adjusted for urinary creatinine was reduced from 0.35 +/- 0.82 to 0.22 +/- 0.55 g/g creatinine (p=0.0119). The urinary protein reduction was observed only in patients with renin-angiotensin inhibition (p=0.0216). By switching from amlodipine to benidipine treatment, more than 80% of patients reduced their blood pressure, and more than 40% achieved optimal blood pressure. Higher urinary protein excretion (p<0.0001), lower glomerular filtration rate (p=0.0011) and presence of diabetes (p=0.0284) were correlated with reduction of urinary proteins during changeover. Taken together, our results suggest that benidipine may have greater efficacy than amlodipine in reducing blood pressure and proteinuria.

Crystal structures of two hemoglobin components from the midge larva Propsilocerus akamusi (Orthocladiinae, Diptera).

The polymorphic components of hemoglobin (Hb) of the midge larva Propsilocerus akamusi were classified into two distinct types dependent on their spectroscopic properties, normal absorption (N) and low absorption (L). Analyses of the amino acid sequences of component VII (N-type Hb) and component V (L-type Hb) from P. akamusi indicated that one remarkable difference is the replacement of the distal histidine (His) with isoleucine (Ile) in component V. To clarify the structural differences between the two Hb components, we determined the crystal structures of components V and VII at resolutions of 1.64 A and 1.50 A, respectively. These crystal structures indicated a short additional helix comprising three amino acid residues at the C-terminal region in component V, and a typical globin fold including eight helices in component VII. Comparison of the heme regions of the Hb components suggests that the structural changes of the heme region in component V on ligation differ from that of usual Hb.

Renal protective effect in hypertensive patients: the high doses of angiotensin II receptor blocker (HARB) study.

Angiotensin receptor blockers (ARBs) are the recommended first-line antihypertensive treatment for managing chronic kidney disease, and strict blood pressure (BP) regulation is crucial for the reduction of proteinuria. Valsartan and candesartan are commonly used ARBs in Japan, with maximum permissible doses of 160 mg/day and 12 mg/day, respectively. We evaluated BP and proteinuria after changeover from the maximum dose of candesartan to the maximum dose of valsartan, in 55 poorly controlled hypertensive patients undergoing candesartan treatment who were unable to achieve optimal BP according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). We measured BP and pulse rate and assessed urinary protein excretion (UPE) before and after changeover. Changeover was associated with decreases in systolic BP and diastolic BP from 158/89 mmHg to 150/86 mmHg (p<0.01). Changeover was also associated with a reduction in UPE adjusted to urinary creatinine from 0.35+/-0.19 g/g creatinine to 0.19+/-0.37 g/g creatinine (p=0.0271) in patients who had high urinary protein levels prior to changeover without significant decreases in BP (p=0.0184). According to multiple regression analysis, higher UPE (p<0.0001) and a lower glomerular filtration rate (GFR) (p=0.0011) prior to changeover were independently correlated with reduction in UPE. Our results suggest that the maximum dose of valsartan is more effective than the maximum dose of candesartan for reducing BP and proteinuria.