Effect of amino group protonation on the carboxyl group in aqueous glycine observed by O 1s X-ray emission spectroscopy.

The valence electronic structures of the amino acid glycine in aqueous solution were investigated in detail through X-ray emission spectroscopy at O 1s excitation under selective excitation conditions of the C[double bond, length as m-dash]O site in the carboxyl group. The X-ray emission spectra of glycine were similar to that of acetic acid (CH3COOH), suggesting a resemblance between the molecular orbitals associated with the carboxyl groups in the two molecules. The changes of O 1s X-ray emission spectra as a function of pH were investigated in detail. In addition to spectral changes due to protonation/deprotonation of the carboxyl group for lower pH-values around the pKa value (∼2.3), the spectra of glycine exhibited further changes in the higher-pH region near the pKb value of glycine (dissociation constant of amino group ∼9.5). These results show the effects of amino group protonation on the electronic state around the carboxyl group. X-ray emission spectroscopy might be a tool to investigate intramolecular interactions between functional groups in a molecule.

Resonant inelastic x-ray scattering and photoemission measurement of O2: Direct evidence for dependence of Rydberg-valence mixing on vibrational states in O 1s → Rydberg states.

High-resolution resonant inelastic x-ray scattering (RIXS) and low-energy photoemission spectra of oxygen molecules have been measured for investigating the electronic structure of Rydberg states in the O 1s → σ* energy region. The electronic characteristics of each Rydberg state have been successfully observed, and new assignments are made for several states. The RIXS spectra clearly show that vibrational excitation is very sensitive to the electronic characteristics because of Rydberg-valence mixing and vibronic coupling in O2. This observation constitutes direct experimental evidence that the Rydberg-valence mixing characteristic depends on the vibrational excitation near the avoided crossing of potential surfaces. We also measured the photoemission spectra of metastable oxygen atoms (O*) from O2 excited to 1s → Rydberg states. The broadening of the 4p Rydberg states of O* has been found with isotropic behavior, implying that excited oxygen molecules undergo dissociation with a lifetime of the order of 10 fs in 1s → Rydberg states.

Triple-path collector optics for grazing incident x-ray emission spectrometer.

A new type of collector optics was developed for grazing incident x-ray emission spectrometer. The collector optics used two cylindrical mirrors to add two extra light paths while keeping the center light path that directly illuminates the grating. The design and properties of the spectrometer using the triple-path collector optics were evaluated using ray-tracing simulations, and validity of this design in terms of throughput and energy resolution was confirmed by the experimentally obtained spectra.

The inhomogeneous structure of water at ambient conditions.

Small-angle X-ray scattering (SAXS) is used to demonstrate the presence of density fluctuations in ambient water on a physical length-scale of approximately 1 nm; this is retained with decreasing temperature while the magnitude is enhanced. In contrast, the magnitude of fluctuations in a normal liquid, such as CCl(4), exhibits no enhancement with decreasing temperature, as is also the case for water from molecular dynamics simulations under ambient conditions. Based on X-ray emission spectroscopy and X-ray Raman scattering data we propose that the density difference contrast in SAXS is due to fluctuations between tetrahedral-like and hydrogen-bond distorted structures related to, respectively, low and high density water. We combine our experimental observations to propose a model of water as a temperature-dependent, fluctuating equilibrium between the two types of local structures driven by incommensurate requirements for minimizing enthalpy (strong near-tetrahedral hydrogen-bonds) and maximizing entropy (nondirectional H-bonds and disorder). The present results provide experimental evidence that the extreme differences anticipated in the hydrogen-bonding environment in the deeply supercooled regime surprisingly remain in bulk water even at conditions ranging from ambient up to close to the boiling point.

Expression and role of mannose receptor/terminal high-mannose type oligosaccharide on osteoclast precursors during osteoclast formation.

Osteoclasts are formed from hematopoietic precursors via cell-cell fusion. We have previously reported that mannose residues are expressed on the outer membranes of monocytes during osteoclast differentiation. In the present study, we have attempted to demonstrate the pattern of expression levels of terminal high-mannose type oligosaccharide and to show that the mannose receptor is expressed on osteoclast precursor cells. Osteoclasts were formed using three different systems, namely mouse bone marrow cell culture, co-culture of mouse spleen cells with stromal cells, and RAW264.7 cell cultures. During osteoclast differentiation, the expression of terminal high-mannose type oligosaccharide gradually increased and then peaked at the stage of fusion in all three systems. Expression of the mannose receptor gradually increased during osteoclast differentiation in bone marrow cells and the co-culture system. In contrast, that in RAW264.7 cells had already been detected in the absence of the soluble receptor activator of NF-kappaB ligand and did not change during osteoclast differentiation. To ascertain whether expression of high-mannose type oligosaccharide is involved in tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation, glycosidase inhibitors were used on RAW264.7 cell culture. Castanospermine, an inhibitor of glucosidase I, inhibited the TRAP-positive MNCs, and deoxymannojirimycin, an inhibitor of alpha-mannosidase I, increased the TRAP-positive MNC formation. These results indicate that the binding of terminal high-mannose and mannose receptor is important for the process of cellular fusion in osteoclast formation.

Left ventricular diastolic function in the elderly.

Previous studies using pulsed Doppler echocardiography have demonstrated a pattern of abnormal left ventricular relaxation associated with increasing age. Specifically, aging is associated with decreased peak velocity of early diastolic mitral inflow, increased peak velocity of late diastolic inflow, increased isovolumic relaxation time, and early diastolic deceleration time. Abnormal relaxation can progress to significantly elevated left atrial pressure--characterized by increased early peak velocity and shortened isovolumic relaxation time and deceleration time--as part of the disease processes. Left ventricular diastolic dysfunction is highly prevalent, occurring in one half to two thirds of elderly patients with congestive heart failure, in association with normal systolic function. Left ventricular hypertrophy, which is commonly related to systemic arterial hypertension, and ischemic heart disease are the two major causes of abnormal left ventricular diastolic function in the elderly. Recently, newer echocardiographic techniques have been described that allow more accurate evaluation of left ventricular diastolic function. Treatments for left ventricular diastolic dysfunction should focus on the underlying disease etiology as well as on the derangement in left ventricular diastolic function. Although calcium channel blockers and angiotensin-converting enzyme inhibitors have been used clinically to treat diastolic dysfunction, their effects on prognosis remain unproven.

Invasive pulmonary aspergillosis with thrombosis in the left atrium.

We report a female patient with left atrial wall invasion from pulmonary aspergillosis. She had been treated for diabetes mellitus. Pulmonary aspergillosis extended to the left atrial wall via the left pulmonary vein and formed a polypoid lesion in the left atrium. The polypoid lesion was composed of thrombus, and the thrombus increased in size to become large, and it showed invagination into the mitral valve during diastole. We considered that the thrombus was formed on the injured endocardium. Severe invasive aspergillosis thus could occur in a mild systemic immunocompromised host.

Simple method for estimating regurgitant volume with use of a single radius for measuring proximal isovelocity surface area: an in vitro study of simulated mitral regurgitation.

The proximal isovelocity surface area (PISA) color Doppler method with use of a hemielliptic formula is reported to be accurate for quantitating regurgitant volume (RV). However, this formula ideally requires the measurement of 2 or 3 radii and therefore is not widely used clinically. The purpose of this in vitro study was to derive a simple PISA formula for estimating RV with use of a single radius axial to the valve orifice and to compare it with the clinically used single-radius hemispherical formula (2 x pi R(2) x AV x TVI/Vp), where AV is the apparent color Doppler aliasing velocity, R is the PISA color Doppler aliasing radius, TVI is time-velocity integral of the jet by continuous wave Doppler, and Vp is the peak velocity of the jet by continuous wave Doppler. Pulsatile flow studies were performed across a convex curvilinear surface, which more closely approximates the shape of the mitral valve than does a planar surface. Pulse rates (60 to 80 bpm), peak flow velocities (4.0 to 6.0 m/s), and regurgitant orifice areas (0.2 to 1.0 cm(2)) were varied to simulate mitral regurgitation. The AVs were varied from 11 to 39 cm/s, and a single PISA aliasing radius was measured at each AV. Excellent linear correlations were obtained between the PISA radius and the actual RV measured with use of a beaker (r = 0.94 to 0.97, P <.0001). A series of simplified formulas was derived from the regression line of the PISA radius versus the RV. For example, with an AV of 21 cm/s, RV was estimated by a simplified PISA formula (where RV[mL] = 10 x R [mm] - 30) with an accuracy of 3.3 +/- 6.3 mL versus -20.3 +/- 8.7 mL for the standard single-radius PISA method (P <.0001). By using the standard single-radius hemispherical PISA formula, RV was underestimated if the radius was <20 mm. By using simplified regression equations, the PISA radius accurately estimated RV at a PISA radius <20 mm. Clinical studies are necessary to validate this concept.

Low extracellular Mg2+ concentrations suppress phagocytosis in vitro by alveolar macrophages from rats.

The aim of this study was to assess the effects of extracellular Mg2+ concentrations on phagocytosis in vitro by alveolar macrophages from rats. Phagocytosis was suppressed in the presence of low, but not high, Mg2+ concentrations. Vanadate, a Mg(2+)-ATPase inhibitor, suppressed phagocytosis. In the presence of a low Mg2+ concentration or vanadate, the cytosolic free Ca2+ concentration ([Ca2+]i) increased, but the cytosolic free Mg2+ concentration did not. These results suggest that low extracellular Mg2+ concentrations and vanadate suppress phagocytosis by rat alveolar macrophages by increasing [Ca2+]i.

Left atrial systolic function assessed by left atrial ejection force in patients with sick sinus syndrome and paroxysmal atrial fibrillation.

We evaluated left atrial systolic function using left atrial ejection force (LAEF) in 19 patients with sick sinus syndrome (SSS) and in 20 with paroxysmal atrial fibrillation (Paf) whose ages ranged from 48 to 80 years. We also evaluated 35 normal individuals for comparison. The LAEF was calculated as 1/3 x mitral valve area x (peak velocity of A wave)2 using two-dimensional and pulsed-Doppler echocardiography according to Newton's law of motion and hydrodynamics. In normal individuals, LAEF positively correlated with age (r = 0.82, p < 0.01). Normal LAEF was calculated as 0.098 x age - 0.74 (kdynes) from the regression line. Because of this correlation, we used age-corrected LAEF (%LAEF) that was calculated as (measured LAEF / normal LAEF) x 100. The results showed that this value was 53+/-26% in patients with SSS and 54+/-26% in patients with Paf. Both were significantly lower than normal individuals (p < 0.001). Among SSS subtypes, %LAEF was lower in types II and III than in type I (51+/-14%, 37+/-19%, and 81+/-35%, respectively). In conclusion, left atrial systolic function is depressed in patients with Paf and SSS, in particular, types II and III. These results suggest that the pathological abnormalities extend not only to the sinus node but also to the left atrial muscle in patients with SSS and Paf.

Estimation of the systolic pulmonary arterial pressure using contrast-enhanced continuous-wave Doppler in patients with trivial tricuspid regurgitation.

Noninvasive estimation of pulmonary arterial pressure is important for hemodynamic monitoring of patients with heart disease. In patients with tricuspid regurgitation (TR), the peak velocity of TR on continuous-wave (CW) Doppler can be used to estimate the systolic pulmonary arterial pressure (PAPs) using the simplified Bernoulli equation. We evaluated a new technique of contrast-enhanced CW Doppler for calculating PAPs in patients with trivial TR. Forty-one patients without visible TR detected by color Doppler, pulsed Doppler or CW Doppler were evaluated. Age ranged from 19 to 73 (55 +/- 12) years old. Tricuspid flow signals were recorded on CW Doppler after intravenous administration of indocyanin green (ICG) or Albunex. PAPs was calculated as; PAPs = 4 x VTR2 + 10 mmHg, where VTR is the peak velocity of TR. PAPs calculated using contrast-enhanced CW Doppler was compared with PAPs measured by the following cardiac catheterization. 1) TR signals were recorded using the contrast-enhanced CW Doppler technique in 39 of 41 patients (95%) after intravenous administration of contrast agents. 2) The error of estimate of PAPs using the contrast-enhanced CW Doppler technique was -2.4 +/- 7.5 mmHg, and the percent error was -10.7 +/- 32.4% in all patients. In 20 of 39 patients (51%), the error of estimate was within +/- 5 mmHg. 3) PAPs was overestimated by 12.2 +/- 6.1 mmHg in patients with good contrast enhancement of TR signals. The contrast-enhanced CW Doppler technique is useful for estimating PAPs noninvasively in patients with trivial TR. It is better to assume the right atrial pressure as 3-5 mmHg, not 10 mmHg, in patients with good enhancement of trivial TR. Physiological TR may be enhanced by contrast agents in these patients.

Mental stress test is an effective inducer of vasospastic angina pectoris: comparison with cold pressor, hyperventilation and master two-step exercise test.

BACKGROUND: Cold pressor, hyperventilation and exercise stress tests were usually used for inducing an angina attack in patients with vasospastic angina pectoris. We induced vasospastic angina attack using the mental calculation stress test, and compared the results with those using other stress tests. SUBJECTS AND METHODS: Subjects were 29 patients with vasospastic angina pectoris. Their ages were 60.8+/-8.4 years. Coronary vasospasm was induced by an acetylcholine infusion test during coronary angiography. The mental stress test was performed as follows; after memorizing six digits numbers, they repeated these numbers in reverse for 5 min, and performed serial subtraction of 17 from 1000 for 5 min. Blood pressure, heart rate and ECG were recorded every 1-5 min during the mental stress test. The serum concentrations of epinephrine and norepinephrine were measured before and during the mental stress test. We compared these results with those obtained using cold pressor, hyperventilation and the Master two-step exercise stress test. RESULTS: (1) Eight of the 29 patients (28%) showed ischemic ST-T change, which was caused by the mental stress test. (2) The increase in norepinephrine was greater in patients with an ST-T change than without an ST-T change (0.11+/-0.06 vs. 0.04+/-0.04 ng/ml, P<0.01). (3) The incidence of the ST-T change caused by the mental stress test (28%) was similar to the cold pressor test (27%) and greater than that caused by the hyperventilation test (13%). The incidence of ST-T change caused by the Master two-step test was 55%. CONCLUSIONS: The mental stress test is an effective inducer of vasospastic angina attack, and attack may be induced by neurohumoral vasoconstrictive reflex and/or increased left ventricular afterload.

Effect of ticlopidine on exercise-induced platelet aggregation and exercise tolerance time in patients with ischemic heart disease.

Platelet aggregation is one of the most important mechanisms for acute myocardial infarction during exercise. We sought to evaluate the effect of ticlopidine (TP) on platelet aggregation (PA) during exercise in patients with ischemic heart disease (IHD). We studied 38 patients with IHD, 26 patients with effort angina pectoris, and 12 patients with a previous myocardial infarction. In protocol I, subjects were divided into two groups. Drugs altering platelet aggregation were withheld 2-4 weeks before the study in 25 patients (control group). TP (200 mg/day) was administered for 7 days in 13 patients (ticlopidine group). A symptom-limited modified Bruce protocol treadmill exercise test was performed. PA was measured at rest and after exercise by using optical densitometry induced by adenosine diphosphate (ADP). PA ratio (percentage of maximum) was compared. In protocol II, in 12 patients, treadmill exercise test and PA measurement were performed with and without TP. PA significantly increased after exercise in control (from 51.7+/-23.3% to 64.4+/-27.7%, p < 0.01) and ticlopidine (from 31.9+/-10.5% to 42.0+/-20.4%, p < .01) groups; however, its grade was lower in the ticlopidine group than in the control group. After exercise, PA was lower in the ticlopidine group than in control group (42.0+/-20.4% vs. 64.4+/-27.7%; p < 0.01). In the same patients, PA was lower with TP than without TP after exercise. Treadmill exercise-tolerance time was greater in the ticlopidine group than in the control group, but not statistically significant (762.3+/-139.2 vs. 711.6+/-169.6 s; NS). Exercise-tolerance time was significantly greater with TP than without TP in same patient (791.7+/-98.9 vs. 733.3+/-152.8 s; p < .05). TP suppressed the increase of PA during exercise and increased the exercise-tolerance time in patients with IHD.

An elderly man with Klinefelter syndrome associated with hypertrophic cardiomyopathy, sick sinus syndrome, and coronary arteriovenous fistula.

Hypertrophic cardiomyopathy (HCM) is a rare cardiac complication in patients with Klinefelter syndrome. We report the case of a 67-year-old Japanese man with Klinefelter syndrome, HCM, sick sinus syndrome, and coronary arteriovenous fistula, in whom the 47XXY/46XY mosaic pattern was revealed by chromosomal study. Echocardiography revealed HCM with an interventricular septum thickness of 17 mm and a left ventricular posterior wall thickness of 10 mm. Sick sinus syndrome type III was diagnosed by paroxysmal atrial fibrillation (longest sinus arrest 9.0 sec) on 24-h Holter ECG recording. Coronary arteriovenous fistula was detected from the left anterior descending artery to the right ventricle by coronary arteriography. To our knowledge, this is the first case report of Klinefelter syndrome with HCM. As there have been a few reports of patients with Klinefelter syndrome in association with skeletal muscular diseases such as Becker-type muscular dystrophy or myotonic dystrophy, the gene mutation that causes Klinefelter syndrome may occur in the cardiac muscle. HCM may represent another variable expression of this chromosomal abnormality.

[The diagnostic value of thoracoscopic examinations in tuberculous pleurisy].

We evaluated the diagnostic value of thoracoscopic examinations in eleven patients who had pleural effusion and were diagnosed as tuberculous pleurisy. The characteristic white or yellowish-white micronodules were observed by thoracoscopy in eight patients and all their biopsied tissue were compatible with tuberculosis. We had some cases which were not determined as tuberculous pleurisy from bacteriological examinations and were determined only from the thoracoscopic findings.

Involvement of prostaglandin endoperoxide H synthase-2 in osteoclast formation induced by parathyroid hormone.

Prostaglandin (PG)E2 is one of the most important endogenous bone resorbing factors. In the previous study, we demonstrated that osteoclast formation induced by IL-1 beta was mediated by PGE2 produced by induced prostaglandin endoperoxide H synthase-2 (PGHS-2) in osteoclastic cells. In the same bone marrow culture system, indomethacin also suppressed the osteoclast formation induced by PTH. The inhibition was abolished by exogenously added PGE2 at dose as low as 3 x 10(-9) M, which was too low to elevate the intracellular cAMP and calcium levels and also it was too low to cause osteoclast formation by itself. In order to estimate what kind of cell produced such small amount of PGE2 in the PTH treatment, we carried out antibody staining of PGHS-1&PGHS-2 and PGHS activity in the intact bone marrow cells. PTH was found to induce PGHS activity in tartrate-resistant acid phosphatase (TRACP) positive mononuclear cells and the PGHS activity was inhibited by NS-398, a specific inhibitor of PGHS-2. Immunocytochemical staining supported the expression of PGHS-2 in TRACP-positive mononuclear cells. These findings suggest that PGHS-2 induced by PTH may regulate osteoclast formation by different mechanism from that induced by IL-1 beta.

Contrast-enhanced radiographic computed tomographic findings in patients with straight back syndrome.

UNLABELLED: Straight back syndrome (SBS) is usually diagnosed by physical and chest radiographic findings. Radiographic computed tomographic (CT) findings are very useful for the diagnosis and the evaluation of its severity. The purpose is to evaluate the relationship between chest X-ray film and CT findings. SUBJECTS: We evaluated 26 patients (SBS group) and 11 normal subjects (control group). SBS group consisted of 15 patients without structural heart disease (group I) and 11 patients with other heart disease (group II). METHODS: (1) On the chest X-ray film, antero-posterior diameter (APD) of the thorax, transthoracic diameter (TTD), and APD/TTD ratio were measured. (2) On the CT image, three parameters were calculated; APD of the left atrium (LA diameter), APD/transverse diameter ratio of the heart (flattening ratio) and left side shift ratio of the heart (shifting ratio). (3) CT parameters were compared with APD/TTD ratio in patients and control group. RESULTS: (1) APD/TTD ratio was smaller in group I and II than control group (30.0 +/- 5.4, 30.5 +/- 4.0 v 44.6 +/- 2.7%, p < .001). (2) LA diameter was smaller in group I and II than control group (23.2 +/- 4.1, 26.0 +/- 8.6 v 30.0 +/- 6.5 mm, p < .01). Flattening ratio was also smaller in group I and II than control group (59.2 +/- 9.4, 61.8 +/- 8.6 v 75.4 +/- 13.2%, p < .01). Shifting ratio was greater in group I and II than control group (10.9 +/- 5.0, 11.9 +/- 4.5 v 8.4 +/- 4.0%, p < .01). (3) APD/TTD ratio correlated with LA diameter (r = .39, p < .05) and flattening ratio (r = .53, p < .001). APD/TTD ratio did not correlate with shifting ratio (r = -.27, NS). CONCLUSIONS: APD/TTD ratio correlated with LA diameter and flattening ratio rather than shifting ratio. LA diameter and flattening ratio on the CT image were more useful for evaluating the severity.

Short- and long-term effects of nisoldipine on cardiac function and exercise tolerance in patients with hypertrophic cardiomyopathy.

UNLABELLED: Nisoldipine is a second generation dihydropyridine calcium antagonist having characteristics of strong coronary artery dilating effect and less negative inotropic action. The purpose of this study was to evaluate the effect of nisoldipine on the cardiac function (systolic and diastolic) and the exercise tolerance, in patients with hypertrophic cardiomyopathy (HCM). SUBJECTS: Twenty-three patients with HCM were studied. METHODS: We measured the following indices using M-mode and pulsed wave Doppler echocardiography before and after nisoldipine therapy; left ventricular fractional shortening (LVFS), isometric relaxation time (IRT), deceleration half-time (DHT) of early diastolic mitral (E) flow, late diastolic mitral (A) flow and A/E ratio. Symptom-limited treadmill exercise test was performed. Exercise tolerance (EX) time was measured. Nisoldipine of 10 mg/day was orally administered. Same tests were repeated on day 14 and after 6 months. RESULTS: 1) Short-term effects; LVFS did not change (55.9 +/- 5.9%-->57.0 +/- 7.4%, NS) after 2 weeks. However, LV diastolic function significantly improved (IRT; 92.1 +/- 7.7 ms-->85.2 +/- 11.6 ms, p < 0.05, DHT; 70.7 +/- 16.2 ms-->63.3 +/- 3.7 ms, p < 0.05). EX time increased (8.9 +/- 2.6 min-->10.0 +/- 3.3 min, p < 0.05), 2) Long-term effects; LV diastolic function had a tendency toward improvement, but is statistically not significant (IRT; 91.1 +/- 7.6-->83.8 +/- 11.6 ms, DHT; 73.1 +/- 23.4-->61.0 +/- 11.4 ms, A/E; 1.26 +/- 0.29-->1.11 +/- 0.36) after 6 months. EX time was significantly increased (9.4 +/- 1.7--> 10.1 +/- 1.7 min, p < 0.05). CONCLUSIONS: Nisoldipine improved LV diastolic dysfunction and exercise tolerance in patients with HCM. These effects were similar to the first generation calcium antagonists. LV diastolic dysfunction may be improved due to the reduction of intracellular calcium concentration and the relief of myocardial ischemia by strong coronary artery dilating effect. However, nisoldipine did not affect the LV systolic function because of its less negative inotropic effect.