[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.

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.

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.

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 .

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.

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.

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.

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.

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.

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 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.

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.

A disulfide bridge mediated by cysteine 574 is formed in the dimer of the 70-kDa heat shock protein.

The 70-kDa heat shock protein (Hsp70) is predominantly present intracellularly as a monomer, but a small population is converted to dimers and oligomers under certain conditions. In the present study, we investigated the dimeric structure of human inducible Hsp70. As reported earlier, the C-terminal client-binding domain (amino acids 382-641) was required for the dimerization. A 40-amino acid deletion in the client-binding domain from either the N-terminus or C-terminus greatly enhanced the dimerization potential of Hsp70. Limited proteolysis indicated that the dimer formed through truncation from the C-terminus had a conformation similar to that of the non-truncated form. Truncation experiments demonstrated that the client-binding sub-domain (amino acids 382-520) with its adjacent region up to amino acid 541 was not sufficient for the dimerization but that the region up to amino acid 561 was sufficient. Interestingly, the dimer formed through truncation from the C-terminus acquired a homomeric disulfide bridge at Cys574.

Clinical usefulness and limitations of brachial-ankle pulse wave velocity in the evaluation of cardiovascular complications in hypertensive patients.

The goal of this study was to clarify the clinical usefulness and limitations of brachial-ankle pulse wave velocity (PWV) to evaluate hypertensive complications, in comparison with carotid-femoral PWV. Patients with essential hypertension (n=296, male/female=161/135; age=61.1+/-0.7 years) were enrolled. We measured brachial-ankle PWV, femoral-ankle PWV and carotid-femoral PWV simultaneously, and evaluated target organ damage and associated clinical conditions (cerebrovascular and cardiovascular disease) using the World Health Organization classification modified in 1999. Carotid-femoral PWV (p<0.0001; r=0.521) and brachial-ankle PWV (p<0.0001; r=0.478) but not femoral-ankle PWV were significantly correlated with age. Carotid-femoral PWV was significantly higher in patients with associated clinical conditions compared with that in patients with target organ damage (p<0.05) and those with no complications (p<0.0001). Brachial-ankle PWV was significantly higher in patients with associated clinical conditions (p<0.05) and target organ damage (p<0.05) compared to those with no complications, but there was no significant difference in brachial-ankle PWV between these two groups. Moreover, femoral-ankle PWV was significantly lower in patients with associated clinical conditions compared with that in patients with target organ damage (p<0.05). These data suggest that brachial-ankle PWV could underestimate arterial stiffness in hypertensive patients with a history of cardiovascular events.

Evaluation of morning blood pressure elevation and autonomic nervous activity in hypertensive patients using wavelet transform of heart rate variability.

To evaluate morning autonomic nervous activity and blood pressure profiles in hypertensive patients by analyzing heart rate variability and ambulatory blood pressure. Data from 82 patients with untreated essential hypertension were analyzed. We evaluated the 24-h profile of blood pressure and that of indices of autonomic nervous activity, i.e., the high frequency component (HF) and low frequency component/HF (LF/HF), which were obtained by wavelet transform of heart rate variability. Patients were classified by dipping status (nondippers, n=28; dippers, n=32; extreme-dippers, n=8; and risers, n=14) and morning blood pressure profile (large, n=9; small, n=60; and inverted, n=13). Nocturnal systolic blood pressure in extreme-dippers was significantly lower than that in the other groups; that in the risers was significantly higher (p<0.05). There were no significant group differences in daytime systolic blood pressure. Daytime and 24-h HF levels were significantly higher in the dipper vs. the riser group (p<0.05). Morning blood pressure elevation negatively correlated to preawake (p<0.01) and nocturnal blood pressure (p<0.05), but not to daytime and post-awake blood pressure. The preawake/postawake ratio of systolic blood pressure positively correlated to that of LF/HF (p<0.01) and negatively correlated to preawake HF levels (p<0.05). Multivariate regression analysis revealed that preawake HF levels (p=0.037) and preawake/postawake ratio of LF/HF (p=0.033) were independently correlated with morning blood pressure elevation ratio. Our results suggest that activation of HF before waking and LF/HF during waking might play an important role in the development of morning blood pressure elevation.

Genetic influences of beta-adrenoceptor polymorphisms on arterial functional changes and cardiac remodeling in hypertensive patients.

Three subtypes of beta-adrenoceptor, beta1, beta2 and beta3, are involved in the sympathetic nervous system, which plays an important role in the development of hypertension and hypertensive complications. These complications can include left ventricular hypertrophy and arterial stiffness, which are reported risk factors for cardiovascular diseases. We designed clinical trials to clarify the association between hypertensive complications and beta-adrenoceptor single nucleotide polymorphisms in essential hypertension. Using Taqman PCR methods, we detected five polymorphisms of three beta-adrenoceptors: Ser49Gly and Arg389Gly for the beta1-adrenoceptor; Gly16Arg and Glu27Gln for the beta2-adrenoceptor; and Trp64Arg for the beta3-adrenoceptor. We included 300 subjects and measured pulse wave velocity, vasodilator response to hyperemia, left ventricular hypertrophy (by electrocardiogram and echocardiography), and cardiac enlargement (by chest X-ray). We found that pulse wave velocity and nitroglycerin-induced hyperemia were both closely associated with the Ser49Gly polymorphism (p<0.05), and Glu27Gln was found by both electrocardiogram and echocardiography to be significantly associated with left ventricular hypertrophy (p<0.05). These data suggested that two polymorphisms of different beta-adrenoreceptor subtypes are the genetic influences on the development of arterial stiffness and left ventricular hypertrophy in essential hypertension.

Serum interleukin-15 concentration in patients with essential hypertension.

BACKGROUND: Interleukin (IL)-15 is one of the cytokines produced by neutrophils and monocytes/macrophages, and its expression is found immunohistochemically in inflammatory cells adjacent to vulnerable atherosclerotic plaques. However, the influence of systemic IL-15 on cardiovascular disease is still unclear. Therefore, we designed clinical investigations to clarify the relationship between cardiovascular complications and serum IL-15 levels. METHODS AND RESULTS: Three hundred ninety-nine patients with essential hypertension were analyzed. We divided the study subjects into the following three groups according to the modified World Health Organization-International Society of Hypertension classification of 1999: patients with no organ damage (n = 213), patients with mild organ damage (n = 128), and patients with severe organ damage (n = 58). We measured serum IL-15, highly sensitive C reactive protein, IL-6, soluble intercellular adhesion molecule, and soluble vascular cell adhesion molecule levels. Serum IL-15 concentration in patients with severe organ damage was significantly higher than that in those with no organ damage (P < .01) and those with mild organ damage (P < .01). Serum IL-15 concentration in patients with coronary artery disease or peripheral artery disease was significantly higher than that in those without coronary artery disease or peripheral artery disease. Moreover, serum IL-15 concentration in patients with lacunar infarction was significantly higher than that in those without lacunar infarction (P < .005). By multiple linear logistic regression analysis, serum IL-15 concentration was independently correlated with cardiovascular disease. CONCLUSIONS: These data suggest that a systemic inflammatory response involving IL-15 might be involved in the occurrence of cardiovascular disease in patients with essential hypertension.

Evidence of met-form myoglobin from Theliostyla albicilla radular muscle.

Gastropod mollusc myoglobins provide interesting clues to the evolution of this family of proteins. In addition to conventional monomeric myoglobins, this group also has dimeric and unusual indoleamine dioxygenase-like myoglobins. We isolated myoglobin from the radular muscle of living gastropod mollusc Theliostyla albicilla. The myoglobin appeared to be present in an oxidized met-form, a physiologically inactive form that is not capable of binding oxygen. Under the same extraction conditions, myoglobins mainly of the physiologically active oxy-form have been isolated from other molluscs. The complete amino acid sequence of 157 residues of Theliostyla myoglobin shows that it has a long N-terminal extension of seven residues and contains three functional key residues: CD1-Phe, E7-His, and F8-His. The metmyoglobin can easily be reduced to a ferrous state with Na(2)S(2)O(4). The autoxidation rate of the oxy-form was comparable to other molluscan myoglobins over a wide pH range, and Theliostyla myoglobin was shown to be stable as an oxygen-binding protein. Thus, the predominantly met-form of myoglobin in Theliostyla can be attributed to the incomplete functioning of the myoglobin reduction system in the radular muscle. Although the function of Theliostyla myoglobin is unclear, it may be a scavenger of H(2)O(2).

The structural organization of ascidian Halocynthia roretzi troponin I genes.

The organization of troponin I (TnI) genes from the ascidian Halocynthia roretzi have been determined. Halocynthia possesses roughly two types of TnI isoforms. One type is a single-copied adult TnI (adTnI) gene, which contains eight exons and seven introns. adTnI expresses two isoforms, the shorter body wall muscle TnI and the longer cardiac TnI, through alternative splicing. The mRNAs of these TnI isoforms may undergo trans-splicing of the 5'-leader sequences, like the TnI mRNA of another ascidian species, Ciona intestinalis. The other type comprises multi-copied larval TnI (laTnI) genes. Halocynthia has at least three laTnIs (alpha, beta, and gamma), which are composed of five exons and four introns, and two of them (alpha and gamma) are clustered in tandem. All laTnIs have B- and M-regions within their 5'-upstream regions, which have been discovered to be the regulatory elements of Halocynthia larval actin genes. The expression of Halocynthia laTnIs and larval actins may be regulated in the same manner. It is known that Ciona does not possess a larva-specific TnI isoform. The phylogenetic tree of ascidian TnIs suggests that laTnIs might have only been generated within the Pleurogona lineage after Enterogona/Pleurogona divergence, and this scenario well agrees with the absence of laTnIs in Ciona.