Structural insight into the Staphylococcus aureus ATP-driven exporter of virulent peptide toxins.

Staphylococcus aureus is a major human pathogen that has acquired alarming broad-spectrum antibiotic resistance. One group of secreted toxins with key roles during infection is the phenol-soluble modulins (PSMs). PSMs are amphipathic, membrane-destructive cytolytic peptides that are exported to the host-cell environment by a designated adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, the PSM transporter (PmtABCD). Here, we demonstrate that the minimal Pmt unit necessary for PSM export is PmtCD and provide its first atomic characterization by single-particle cryo-EM and x-ray crystallography. We have captured the transporter in the ATP-bound state at near atomic resolution, revealing a type II ABC exporter fold, with an additional cytosolic domain. Comparison to a lower-resolution nucleotide-free map displaying an "open" conformation and putative hydrophobic inner chamber of a size able to accommodate the binding of two PSM peptides provides mechanistic insight and sets the foundation for therapeutic design.

Tunable anomalous Hall effect in a nonferromagnetic system.

We measure the low-field Hall resistivity of a magnetically doped two-dimensional electron gas as a function of temperature and electrically gated carrier density. Comparing these results with the carrier density extracted from Shubnikov-de Haas oscillations reveals an excess Hall resistivity that increases with decreasing temperature. This excess Hall resistivity qualitatively tracks the paramagnetic polarization of the sample, in analogy to the ferromagnetic anomalous Hall effect. The data are consistent with skew scattering of carriers by disorder near the crossover to localization.

Electrophysiological characteristics and radiofrequency ablation of focal atrial tachycardia originating from the superior vena cava.

The initiation of focal atrial tachycardia (AT) from the superior vena cava (SVC) remains unclear. In 3 patients (2 females, 1 male; aged 57, 66 and 50 years, respectively) with focal AT arising from different parts of the SVC, the AT occurred spontaneously, rather than being induced by electrical stimulation. The cycle length of the tachycardia was highly variable, ranging between 190 and 300 ms in patient 1, 180 and 320ms in patient 2, and 200 and 300ms in patient 3. The clinical or associated arrhythmias were atrial fibrillation (AF) (patients 1, 3) and atrial flutter (AFL) (patients 2, 3). A presumed SVC potential that was earlier than the activation of all the other mapping sites was recorded during AT at the lower anterior (15-mm above the atriocaval junction), the mid-anterior (25-mm above the atriocaval junction) and the lower posterior aspect of the SVC (17-mm above the atriocaval junction. Radiofrequency (RF) ablation targeting the SVC focus with the SVC potential promptly eliminated the focal AT in all 3 patients. The coexistent typical AFL was ablated, but the AF was not. The follow-up period was 6, 6, and 3 months, respectively, for each of the patients under no antiarrhythmic medication; there has not been a recurrence of symptomatic palpitation. In conclusion, focal electrical firing in the SVC can initiate AT and this type of focal AT is always associated with AFL or AF. RF ablation guided by the presumed SVC potential is safe and highly effective in eliminating the tachycardia.

Electrophysiologic characteristics and ablation of an atypical atrial flutter in the right atrium.

Subeustachian isthmus-dependent typical atrial flutter has been well studied. We demonstrate a case with atypical atrial flutter involving only the base of the right atrium around the inferior vena cava. Entrainment pacing and mapping studies documented a distinct circuit traversing the subeustachian isthmus, propagating through the posterobasal right atrium, and skirting the inferior vena cava. Successful radiofrequency ablation of the arrhythmia was accomplished by creating a linear lesion at the subeustachian isthmus. Mapping of the inferior vena cava region and the demonstration of concealed entrainment are essential steps in establishing the mechanism of the atypical atrial flutter.

Simultaneous alterations of QRS configuration and tachycardia cycle length during radiofrequency ablation of idiopathic left ventricular tachycardia.

Idiopathic left ventricular tachycardia is characterized by a QRS morphology of right bundle branch block pattern and left axis deviation. Alterations in the QRS configuration and tachycardia cycle length, as well as shifting of the earliest activation site occurred after eliminating the original tachycardia by radiofrequency current in an 18-year-old man with idiopathic left ventricular tachycardia. Activation mapping and entrainment mapping during tachycardia identified 2 putative tachycardia exits, 15 mm apart. Elimination of both tachycardias was accomplished after applying radiofrequency current to each exit separately. We proposed that the first radiofrequency application might have altered the exit site and the zone of slow conduction adjacent to the exit site, such that the ventricular tachycardia had a different QRS morphology and became slower in this patient.

Radiofrequency ablation of a right atriofascicular Mahaim fiber and two contralateral left free-wall accessory pathways.

We report a rare combination of a right atriofascicular Mahaim fiber and two left-sided atrioventricular accessory pathways in a 57-year-old female presenting with an antidromic atrioventricular reciprocating tachycardia. Radiofrequency ablation was first targeted at the left lateral accessory pathway that served as the retrograde limb of the tachycardia. After elimination of the left lateral pathway, a bystander left posterolateral pathway was detected, and it too was successfully ablated. Although no tachycardia was reinducible, the Mahaim pathway was ablated because of its short effective refractory period. A discrete Mahaim potential recorded at the right atrial free-wall successfully guided the ablation.

Status of trace elements in patients with idiopathic dilated cardiomyopathy in central Taiwan.

BACKGROUND: Sporadic cases of dilated cardiomyopathy (DCM) are often seen in central Taiwan. Though trace elements may play a role in the pathogenesis of idiopathic DCM, there are no reports concerning study of Taiwan's population in relation to trace elements in patients with DCM. METHODS: Serum selenium, zinc, copper and iron concentrations and blood glutathione peroxidase (GPX) activity were measured in 32 patients with DCM (24 males, 8 females; mean age, 44 +/- 14 years) and 31 age-matched normal volunteers (16 males, 15 females; mean age, 38 +/- 12 years). RESULTS: The average serum selenium concentration of 27.6 +/- 8.4 micrograms/l found in the DCM group was significantly lower than the average concentration of 47.2 +/- 14.7 micrograms/l in the normal group. Blood GPX activity was also significantly lower in the DCM group than in the normal group. Serum selenium concentration correlated well with blood GPX activity in the studied subjects. Serum copper and iron concentrations were significantly higher in the DCM group than in the normal group. There was no difference in serum zinc concentration between the two groups. CONCLUSIONS: Deficiency of serum selenium in association with a low blood GPX activity, and high serum copper and iron concentrations, are found in patients with idiopathic DCM in central Taiwan.

Systemic lupus erythematosus presenting as pleural effusion: report of a case.

Systemic lupus erythematosus (SLE) presenting as a pleural effusion in a young male is not common. This paper describes a 20-year-old man who was admitted to hospital with a spiking fever, chills and cough. A chest x-ray showed alveolar infiltration and a moderate right-sided pleural effusion. The patient was treated for parapneumonic effusion. Thoracentesis was performed and cytology of the aspirated fluid was initially interpreted as showing only numerous polymorphonuclear (PMN) leukocytes. However, in spite of antibiotic treatment the symptoms persisted. A careful review of the cytology specimen showed classic lupus erythematosus (LE) cells in addition to PMN cells. Subsequent investigation, including antinuclear antibodies titer, confirmed the diagnosis of LE pleurisy. Therapy with antibiotics was discontinued and treatment with prednisolone 20 mg daily was begun. There was a rapid clinical response including resolution of the fever and pleural effusion.

The prognostic value of ambulatory blood pressure monitoring in untreated mild-to-moderate hypertensive patients: correlation with echocardiography.

BACKGROUND: Target organ damage by hypertension should be related to the daily duration of blood pressure elevation. METHODS: Thirty-six previously untreated patients with mild to moderate hypertension were examined by 2-D, M-mode, Doppler echocardiography and with 24-hour ambulatory blood pressure monitoring. The resulting parameters were compared with those of normotensive subjects. Elevated BP values during the waking hours (> 125/85 mmHg) and sleeping hours (> 115/80 mmHg) were used to calculate the total percentage of abnormal BP values (load) in each patients. RESULTS: In patients with hypertension, left atrial index and left ventricular mass index were significantly greater than those of normotensive subjects (21 +/- 4 vs 18 +/- 3 mm/m2, p < 0.05; 127 +/- 25 vs 94 +/- 19 gm/m2, p < 0.01). Doppler measurement of diastolic filling velocity was significantly different between the two groups, with an early LV filling velocity lower (38 +/- 11 vs 45 +/- 10 cm/sec, p < 0.05) and a late LV filling velocity higher (50 +/- 9 vs 45 +/- 12 cm/sec, p < 0.05) in the hypertensives. Casual systolic and diastolic BP values did not correlate with cardiac structural and functional variables. There were significantly inverse correlations between both sleeping diastolic blood pressure and sleeping DBP load and fractional shortening (r = -0.39, p < 0.05; r = -0.43, p < 0.01, respectively). CONCLUSIONS: These data showed that the majority of patients with hypertension have either cardiac structural or functional abnormalities, or both. High nocturnal diastolic blood pressure and DBP load may have a more determinant effect on systolic function in mild to moderate hypertensive patients.

Left atrial appendage smoke-like echo in dilated cardiomyopathy: its clinical significance and relation to left atrial appendage function.

To elucidate the clinical significance and pathogenesis of left atrial appendage smoke-like echo in dilated cardiomyopathy (DCM), clinical history and transesophageal echocardiographic assessment of left atrial appendage (LAA) anatomy and function were studied in 18 DCM patients with smoke-like echo (SE), 34 patients with DCM but no smoke-like echo and in 14 age-matched normal subjects. Patients with SE had a larger left atrial appendage area, a lower peak LAA systolic flow velocity (PLAAV), a greater incidence of atrial fibrillation, with both left atrial appendage thrombi and a history of arterial embolic episodes, than did patients without SE. Patients in sinus rhythm with SE had a minimal LAA area (5.0 +/- 3.0 cm2) larger than that in the no SE group (3.0 +/- 1.6 cm2) (p < 0.05), and LAA ejection fraction (18 +/- 10%) and PLAAV (24 +/- 9 cm/sec) less than that in the no SE group (40 +/- 11% and 39 +/- 16 cm/sec, respectively) (P < 0.05). Patients with atrial fibrillation (AF) and SE had PLAAV (15 +/- 6 cm/sec) less than that in AF patients without SE (30 +/- 12 cm/sec) (p < 0.05). It is concluded that smoke-like echo in LAA is an indicator of DCM patients with an increased thromboembolic risk usually associated with dilated and poorly contractile LAA.

Left ventricular reserve of the hypertrophied heart in patients with systemic hypertension and hypertrophic cardiomyopathy--relation to age and left ventricular relative wall thickness.

To determine the effects of aging and concentric hypertrophy on the reserve of the left ventricle (LV), 36 patients with hypertension (HT), 22 with hypertrophic cardiomyopathy (HCM) and 25 age-matched normal subjects (N) were studied by isoproterenol (ISP) infusion echocardiography. The end-diastolic LV relative wall thickness (RWT), fractional shortening (FS), peak mitral flow velocity during the rapid filling phase (R) and atrial systole (A), and the A/R ratio were measured. At rest, the RWT and A/R were larger in groups HT and HCM than in group N. There were no significant differences in age, heart rate (HR), and FS among the groups. The A/R of all groups showed a good positive correlation with increasing age. The A/R of the HT group was also positively correlated with RWT. During ISP infusion, the HR, R, A, A/R and FS increased in all groups. The changes in R and FS were smaller in groups HT and HCM than in group N. The change in HR in groups N and HT, and the change in FS in all groups during ISP infusion were all inversely correlated with increasing age. The change in FS during ISP infusion was inversely correlated with RWT in the HT group, but not in HCM. Thus, it was suggested that the impairment of LV reserve in patients with HCM is not only caused by concentric hypertrophy and the aging process, but also by other myocardial factors.

[Genesis of systolic anterior motion (SAM) of the mitral valve in patients with aortic regurgitation].

This study was performed to evaluate the incidence and genesis of systolic anterior motion (SAM) of the mitral valve apparatus in patients with aortic regurgitation (AR). The study population consisted of 44 patients with non-rheumatic AR, without significant aortic stenosis or mitral regurgitation. The presence and location of SAM in the short-axis view were determined by M-mode echocardiography guided by two-dimensional echocardiography. The extent and direction of the regurgitant jet were decided by pulsed or two-dimensional Doppler echocardiography. SAM was observed in 21 (48%) of the 44 patients, and it was more frequently observed in patients with an etiology of aortic valve prolapse or annuloaortic ectasia than in those of other etiology (10/14 vs 10/30; p less than 0.05). Twenty-eight patients whose regurgitant jet was directed posteriorly and impinged on the mitral valve apparatus had a significantly higher incidence of SAM than did the other 16 patients (18/28 vs 3/16; p less than 0.01). In eight of 10 patients in whom the direction of the regurgitant jet could be precisely observed by two-dimensional Doppler echocardiography. SAM was observed at the place where a regurgitant jet was directed along the anterior mitral valve in the short-axis view. M-mode measurements (LVDd, LVDs, %FS, LVDd-LVDs) of the patients with SAM had greater values than those of patients without SAM.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prognosis of hypertrophic cardiomyopathy: echocardiographic and postmortem histopathologic study of 30 patients].

To clarify the influence of cardiac function of myocardial histologic lesions on the prognosis of hypertrophic cardiomyopathy (HCM), most recent echocardiographic findings of 30 deceased patients were reviewed. In 12 patients, histological sections from the left ventricular transverse plane made at necropsy were examined. According to the main causes of death, patients were categorized into four groups as sudden death (17 cases), heart failure death (four cases), embolic death (four cases), and non-cardiac death (five cases). 1. Clinically, atrial fibrillation and heart failure (NYHA III, IV) were frequently observed in heart failure and embolic groups. 2. Echocardiographically, left ventricular wall thickness did not differ among the four groups, but percent fractional shortening was significantly smaller in heart failure group than in non-cardiac group, and left ventricular end-diastolic dimension (LVDd) and left atrial dimension were significantly greater in heart failure group than in non-cardiac group. The normalized rapid filling rate was less in heart failure, embolic, sudden death and non-cardiac groups in that order. 3. Histopathologically, the mean myocyte diameter (MD) and percent area of disarray (%D) did not differ among the four groups, but % area of massive fibrosis (MF) greater than 2 mm2 was larger in heart failure, embolic, sudden death and non-cardiac groups in that order, especially in heart failure group. 4. Comparison of echocardiographic and histopathological findings: Though MD and %D did not correlate with any echocardiographic indices, %MF correlated significantly with LVDd (r = 0.83, p less than 0.005), and correlated inversely with the normalized rapid filling rate (r = -0.80, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

[Pulsed Doppler echocardiographic findings in 117 professional cyclists].

To investigate the effect of long-term athletic training on the heart, pulsed Doppler echocardiography was performed in 117 male professional cyclists (Group C: 20-59 years of age), and 40 age- and sex-matched untrained normal controls (Group N). According to age, the subjects in each group were categorized in two subgroups: 74 cyclists (Group CI), 20-39 years of age and 43 cyclists (Group CII), 40-59 years of age; 24 control subjects (Group NI), 20-39 years of age and 16 control subjects (Group NII), 40-59 years of age. The average durations as professional cyclists were eight years in Group CI and 29 years in Group CII. The ratios of pre-ejection period to ejection time (LV-PEP/ET, RV-PEP/ET) as obtained from Doppler flow velocity patterns of the left and right ventricles (LV, RV) were used as parameters of systolic function. The peak flow velocities during rapid filling (LV-R, RV-R) and atrial systole (LV-A, RV-A), and the ratio of A to R (LV-A/R, RV-A/R) were used as parameters of diastolic filling dynamics. The parameters of systolic function of both ventricles and those of diastolic filling dynamics of the RV did not differ between Group C and Group N, Group CI and Group NI, and Group CII and Group NII. Study of the diastolic filling dynamics of the LV disclosed that Group C had a significantly higher LV-A/R (p less than 0.05) than did Group N; therefore, no significant differences between Group CI and Group NI, and Group CII had a significantly lower LV-R (p less than 0.005) and a higher LV-A/R (p less than 0.005) than did Group NII. Twenty-four hour ambulatory ECG monitoring was performed for 49 cyclists. Thirty cyclists aged 20-39 years were categorized in two groups according to their LV-A/R values: eight cyclists (Group A) with the LV-A/R greater than the mean + SD value (0.69) in Group NI and 22 cyclists (Group B) with the LV-A/R lower than or equal to 0.69. Nineteen cyclists aged 40-59 years were separated into two groups according to the LV-A/R value: 11 cyclists (Group A) with the LV-A/R values greater than the mean + SD value (0.89) in Group NII, and eight cyclists (Group B) with the LV-A/R equal to or less than 0.89.(ABSTRACT TRUNCATED AT 400 WORDS)