Hindfoot alignment at one year after total knee arthroplasty.

PURPOSE: It has previously been found that valgus hindfoot alignment (HFA) improves 3 weeks following total knee arthroplasty (TKA) for varus knee osteoarthritis (OA). In the present study, HFA was evaluated prior to TKA, as well as 3 weeks and 1 year following TKA. Using these multiple evaluations, the chronological effects of TKA on HFA were investigated. METHODS: The study included 71 patients (73 legs) who underwent TKA for varus knee OA. Radiograph examinations of the entire limb and hindfoot were performed in the standing position prior to TKA, as well as 3 weeks and 1 year following TKA. The varus-valgus angle was used as an indicator of HFA in the coronal plane. Patients were divided into two groups according to the preoperative varus-valgus angle: a hindfoot varus group (varus-valgus angle <76°) and a hindfoot valgus group (varus-valgus angle ≥76°). The changes in the varus-valgus angle were evaluated and compared in both groups. RESULTS: In the hindfoot valgus group, the mean ± standard deviation varus-valgus angle significantly declined from 80.5 ± 3.1° prior to TKA to 78.6 ± 3.7° 3 weeks following TKA and 77.1 ± 2.7° 1 year following TKA. However, in the hindfoot varus group, the mean varus-valgus angle prior to TKA (72.7 ± 2.6°) did not differ significantly from the mean varus-valgus angles 3 weeks (72.3 ± 3.3°) or 1 year (73.5 ± 3.0°) following TKA. CONCLUSIONS: HFA improved chronologically in legs with hindfoot valgus as a result of the alignment compensation ability of the hindfoot following TKA. However, no improvement was noted in legs with hindfoot varus because the alignment compensation ability of the hindfoot had been lost. The patients with hindfoot varus should be attended for ankle pain in the outpatient clinic after TKA. LEVEL OF EVIDENCE: III.

Impact of COVID-19 pandemic on emergency medical system and management strategies in patients with acute coronary syndrome.

The global coronavirus disease-2019 (COVID-19) pandemic is associated with reduced rate of percutaneous coronary intervention (PCI). However, there were a few data showing how emergency medical system (EMS) and management strategies for acute coronary syndrome (ACS) changed during the pandemic. We sought to clarify changes on characteristics, treatments, and in-hospital mortality of patients with ACS transported via EMS between pre- and post-pandemic. We examined consecutive 656 patients with ACS admitted to Sapporo City ACS Network Hospitals between June 2018 and November 2021. The patients were divided into pre- and post-pandemic groups. The number of ACS hospitalizations declined significantly during the pandemic (proportional reduction 66%, coefficient -0.34, 95% CI -0.50 to -0.18, p < 0.001). The median time from an EMS call to hospital was significantly longer in post-pandemic group than in pre-pandemic group (32 [26-39] vs. 29 [25-36] min, p = 0.008). There were no significant differences in the proportion of patients with ACS receiving PCI, and in-hospital mortality between the groups. The COVID-19 pandemic had a significant impact on EMS and management in patients with ACS. Although a significant decline was observed in ACS hospitalizations, the proportion of patients with ACS receiving emergency PCI remained during the pandemic.

Inverse scattering approach based on the field equivalence principle: inversion without a priori information on incident fields.

An inverse scattering approach based on the field equivalence principle is developed for reconstructing the parameters of the medium of a scattering object. A problem equivalent to the original scattering problem but internal to the measurement surface is set up. The equivalent surface currents determined by the measured total-field data rigorously yield the incident fields in the region under test, so the approach does not require explicit knowledge of the incident fields. Taking into account the fact that the equivalent surface currents produce a null field external to the surface, a functional of the medium's parameters is introduced, and a genetic algorithm is applied to minimization of the functional. Numerical simulations for imaging defects in a known dielectric cylinder from only total-field data measured on an observation surface are performed to illustrate the efficacy of the proposed inversion method.

Impact of Chronic Kidney Disease on the Associations of Cardiovascular Biomarkers With Adverse Outcomes in Patients With Suspected or Known Coronary Artery Disease: The EXCEED-J Study.

Background The impact of chronic kidney disease (CKD) on the prognostic utility of cardiovascular biomarkers in high-risk patients remains unclear. Methods and Results We performed a multicenter, prospective cohort study of 3255 patients with suspected or known coronary artery disease (CAD) to investigate whether CKD modifies the prognostic utility of cardiovascular biomarkers. Serum levels of cardiovascular and renal biomarkers, including soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-I (hs-cTnI), cystatin C, and placental growth factor, were measured in 1301 CKD and 1954 patients without CKD. The urine albumin to creatinine ratio (UACR) was measured in patients with CKD. The primary outcome was 3-point MACE (3P-MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all-cause death, cardiovascular death, and 5P-MACE defined as a composite of 3P-MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. After adjustment for clinical confounders, sFlt-1, NT-proBNP, and hs-cTnI, but not other biomarkers, were significantly associated with 3P-MACE, all-cause death, and cardiovascular death in the entire cohort and in patients without CKD. These associations were still significant in CKD only for NT-proBNP and hs-cTnI. NT-proBNP and hs-cTnI were also significantly associated with 5P-MACE in CKD. The UACR was not significantly associated with any outcomes in CKD. NT-proBNP and hs-cTnI added incremental prognostic information for all outcomes to the model with potential clinical confounders in CKD. Conclusions NT-proBNP and hs-cTnI were the most powerful prognostic biomarkers in patients with suspected or known CAD and concomitant CKD.

Soluble vascular endothelial growth factor receptor 2 and prognosis in patients with chronic heart failure.

AIMS: Endothelial cell vascular endothelial growth factor receptor 2 (VEGFR-2) plays a pivotal role in angiogenesis, which induces physiological cardiomyocyte hypertrophy via paracrine signalling between endothelial cells and cardiomyocytes. We investigated whether a decrease in circulating soluble VEGFR-2 (sVEGFR-2) levels is associated with poor prognosis in patients with chronic heart failure (HF). METHODS AND RESULTS: We performed a multicentre prospective cohort study of 1024 consecutive patients with HF, who were admitted to hospitals due to acute decompensated HF and were stabilized after initial management. Serum levels of sVEGFR-2 were measured at discharge. Patients were followed up over 2 years. The outcomes were cardiovascular death, all-cause death, major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death and HF hospitalization, and HF hospitalization. The mean age of the patients was 75.5 (standard deviation, 12.6) years, and 57% were male. Patients with lower sVEGFR-2 levels were older and more likely to be female, and had greater proportions of atrial fibrillation and anaemia, and lower proportions of diabetes, dyslipidaemia, and HF with reduced ejection fraction (<40%). During the follow-up, 113 cardiovascular deaths, 211 all-cause deaths, 350 MACE, and 309 HF hospitalizations occurred. After adjustment for potential clinical confounders and established biomarkers [N-terminal B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein], a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death [hazard ratio (HR), 1.79; 95% confidence interval (CI), 1.16-2.74] and all-cause death (HR, 1.43; 95% CI, 1.04-1.94), but not with MACE (HR, 1.11; 95% CI, 0.86-1.43) or HF hospitalization (HR, 1.03; 95% CI, 0.78-1.35). The stratified analyses revealed that a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death (HR, 1.76; 95% CI, 1.07-2.85) and all-cause death (HR, 1.49; 95% CI, 1.03-2.15) in the high-NT-proBNP group (above the median), but not in the low-NT-proBNP group. Notably, the patients with high-NT-proBNP and low-sVEGFR-2 (below the 25th percentile) had a 2.96-fold higher risk (95% CI, 1.56-5.85) for cardiovascular death and a 2.40-fold higher risk (95% CI, 1.52-3.83) for all-cause death compared with those with low-NT-proBNP and high-sVEGFR-2. CONCLUSIONS: A low sVEGFR-2 value was independently associated with cardiovascular death and all-cause death in patients with chronic HF. These associations were pronounced in those with high NT-proBNP levels.

Positioning an ECG electrode to the dorsal side can record higher amplitude of CMAPs during cryoballoon ablation.

PURPOSE: Phrenic nerve injury (PNI) is one of the important complications during cryoballoon (CB) ablation. Recording diaphragmatic compound motor action potentials (CMAPs) during CB ablation can predict PNI. CMAP monitoring may be inaccurate when CMAP amplitudes are low. We examined the effect of positioning an electrocardiography (ECG) electrode at the dorsal side. METHODS: We retrospectively analyzed the cases of 197 consecutive patients who underwent CB ablation for pulmonary vein isolation (PVI) (April 2016 to December 2018) at our institution. CMAP amplitudes were monitored using two recording methods just before cryoapplication. (a) Conventional method: right-arm ECG electrode positioned 5 cm above the xiphoid on the ventral side; left-arm ECG electrode positioned along the costal margin. (b) Our original method: right-arm electrode positioned 5 cm above the xiphoid on the dorsal side; left-arm electrode positioned along the costal margin. RESULTS: The CMAP amplitude during right phrenic nerve pacing was significantly higher at the dorsal side than the ventral side (0.80 ± 0.31 mV vs 0.66 ± 0.29 mV, P < .01). Similarly, the CMAP amplitude during left phrenic nerve pacing was significantly higher at the dorsal side than the ventral side (0.92 ± 0.39 mV, 0.73 ± 0.37 mV, P < .01). PNI occurred in six patients (3.0%); three patients experienced transient PNI, another three patients experienced persistent PNI, and none developed permanent PNI. CONCLUSIONS: CMAP amplitudes were significantly high at the dorsal side compared to the ventral side. Monitoring phrenic nerve function using an ECG electrode at the dorsal side is a simple and easy procedure.

In-hospital morality associated with acute myocardial infarction was inversely related with the number of coronary risk factors in patients from a Japanese nation-wide real-world database.

BACKGROUND: Hypertension, diabetes, dyslipidemia and smoking are established coronary risk factors for coronary heart disease in the general population. However, in Japanese patients with acute myocardial infarction (AMI), the impact of the number of coronary risk factors on in-hospital morality remains unclear. METHODS: The Japan Acute Myocardial Infarction Registry (JAMIR) is a nationwide real-world database. We examined the association between the number of coronary risk factors and in-hospital mortality. RESULTS: Data were obtained from total of 20462 AMI patients (mean age, 68.8 ± 13.3 years old; 15281 men, 5181 women). The prevalence of hypertension increased with advancing age, while the prevalence of smoking decreased with advancing age. The prevalence of diabetes and dyslipidemia were highest in middle age. A majority (76.9%) of the patients with AMI had at least 1 of these coronary risk factors. Overall, the number of coronary risk factor was relatively less in older subjects and women under 50 years old. Crude in-hospital mortality rates were 10.7%, 10.5%, 7.2%, 5.0% and 4.5% with 0, 1, 2, 3 and 4 risk factors, respectively. After adjusting for age and sex, there was an inverse association between the number of coronary risk factors and the in-hospital mortality (adjusted odds ratio [1.68; 95% confidence interval, 1.20-2.35] among individuals with 0 vs. 4 risk factors). CONCLUSION: In the present study of Japanese patients with AMI, who received modern medical treatment, in-hospital mortality was inversely related to the number of coronary risk factors. To investigate the underlying reasons for these findings, further studies are needed.

Difference in the in-hospital prognosis between ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction with high Killip class: Data from the Japan Acute Myocardial Infarction Registry.

BACKGROUND: ST-segment elevation myocardial infarction is known to be associated with worse short-term outcome than non-ST-segment elevation myocardial infarction. However, whether or not this trend holds true in patients with a high Killip class has been unclear. METHODS: We analyzed 3704 acute myocardial infarction patients with Killip II-IV class from the Japan Acute Myocardial Infarction Registry and compared the short-term outcomes between ST-segment elevation myocardial infarction (n = 2943) and non-ST-segment elevation myocardial infarction (n = 761). In addition, we also performed the same analysis in different age subgroups: <80 years and ≥80 years. RESULTS: In the overall population, there were no significant difference in the in-hospital mortality (20.0% vs 17.1%, p = 0.065) between ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction groups. Patients <80 years of age also showed no difference in the in-hospital mortality (15.7% vs 15.2%, p = 0.807) between ST-segment elevation myocardial infarction (n = 2001) and non-ST-segment elevation myocardial infarction (n = 453) groups, whereas among those ≥80 years of age, ST-segment elevation myocardial infarction (n = 942) was associated with significantly higher in-hospital mortality (29.3% vs 19.8%, p = 0.001) and in-hospital cardiac mortality (23.3% vs 15.0%, p = 0.002) than non-ST-segment elevation myocardial infarction (n = 308). After adjusting for covariates, ST-segment elevation myocardial infarction was a significant predictor for in-hospital mortality (odds ratio 2.117; 95% confidence interval, 1.204-3.722; p = 0.009) in patients ≥80 years of age. CONCLUSION: Among cases of acute myocardial infarction with a high Killip class, there was no marked difference in the short-term outcomes between ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction in younger patients, while ST-segment elevation myocardial infarction showed worse short-term outcomes in elderly patients than non-ST-segment elevation myocardial infarction. Future study identifying the prognostic factors for the specific anticipation intensive cares is needed in this high-risk group.

Difference in the in-hospital prognosis between ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction with high Killip class: Data from the Japan Acute Myocardial Infarction Registry.

BACKGROUND: ST-segment elevation myocardial infarction is known to be associated with worse short-term outcome than non-ST-segment elevation myocardial infarction. However, whether or not this trend holds true in patients with a high Killip class has been unclear. METHODS: We analyzed 3704 acute myocardial infarction patients with Killip II-IV class from the Japan Acute Myocardial Infarction Registry and compared the short-term outcomes between ST-segment elevation myocardial infarction (n = 2943) and non-ST-segment elevation myocardial infarction (n = 761). In addition, we also performed the same analysis in different age subgroups: <80 years and ≥80 years. RESULTS: In the overall population, there were no significant difference in the in-hospital mortality (20.0% vs 17.1%, p = 0.065) between ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction groups. Patients <80 years of age also showed no difference in the in-hospital mortality (15.7% vs 15.2%, p = 0.807) between ST-segment elevation myocardial infarction (n = 2001) and non-ST-segment elevation myocardial infarction (n = 453) groups, whereas among those ≥80 years of age, ST-segment elevation myocardial infarction (n = 942) was associated with significantly higher in-hospital mortality (29.3% vs 19.8%, p = 0.001) and in-hospital cardiac mortality (23.3% vs 15.0%, p = 0.002) than non-ST-segment elevation myocardial infarction (n = 308). After adjusting for covariates, ST-segment elevation myocardial infarction was a significant predictor for in-hospital mortality (odds ratio 2.117; 95% confidence interval, 1.204-3.722; p = 0.009) in patients ≥80 years of age. CONCLUSION: Among cases of acute myocardial infarction with a high Killip class, there was no marked difference in the short-term outcomes between ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction in younger patients, while ST-segment elevation myocardial infarction showed worse short-term outcomes in elderly patients than non-ST-segment elevation myocardial infarction. Future study identifying the prognostic factors for the specific anticipation intensive cares is needed in this high-risk group.

Impact of Smoking Status on Growth Differentiation Factor 15 and Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study.

Background Whether circulating growth differentiation factor 15 (GDF-15) levels differ according to smoking status and whether smoking modifies the relationship between GDF-15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF-15 and the impact of smoking status on the association between GDF-15 and all-cause death. GDF-15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF-15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log-transformed GDF-15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF-15. The prognostic value of GDF-15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.

Distinct Characteristics of VEGF-D and VEGF-C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease.

Background VEGF-D (vascular endothelial growth factor D) and VEGF-C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF-C level is inversely and independently associated with all-cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF-D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF-D was measured. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N-terminal pro-B-type natriuretic peptide, cardiac troponin-I, and high-sensitivity C-reactive protein), and VEGF-C, the VEGF-D level was significantly associated with all-cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF-D, either alone or in combination with VEGF-C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all-cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF-D value seems to independently predict all-cause mortality.

VEGF-C and Mortality in Patients With Suspected or Known Coronary Artery Disease.

Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. However, the relationships of vascular endothelial growth factor-C ( VEGF -C), a central player in lymphangiogenesis, with mortality and cardiovascular events in patients with suspected or known coronary artery disease are unknown. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The primary predictor was serum levels of VEGF -C. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for established risk factors, VEGF -C levels were significantly and inversely associated with all-cause death (hazard ratio for 1- SD increase, 0.69; 95% confidence interval, 0.60-0.80) and cardiovascular death (hazard ratio, 0.67; 95% confidence interval, 0.53-0.87), but not with major adverse cardiovascular events (hazard ratio, 0.85; 95% confidence interval, 0.72-1.01). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF -C levels further improved the prediction of all-cause death, but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within 1717 patients with suspected coronary artery disease. Conclusions In patients with suspected or known coronary artery disease, a low VEGF -C value may independently predict all-cause mortality.

Effects of vitamin K antagonist on aortic valve degeneration in non-valvular atrial fibrillation patients: Prospective 4-year observational study.

BACKGROUND: The prevalence of atrial fibrillation (AF) is high in elder subjects. Our previous observational study suggested that vitamin K antagonist (VKA) promotes aortic valve degeneration, a principal cause of aortic stenosis in the elderly, and that angiotensin receptor blocker (ARB) attenuates its progression. This study aimed to prospectively investigate these observations in non-valvular AF patients. METHODS: Of enrolled 430 patients with calcification on no or one aortic valve leaflet, all of the planned 4-year follow-up data were obtained in 122 non-valvular AF patients treated with warfarin (warfarin group) and 101 patients with cardiovascular diseases and without AF and prescription of warfarin (non-warfarin group). RESULTS: Despite higher atherosclerotic risks in the non-warfarin group, 2 or 3 newly calcified leaflets emerged during 4years in 18.0% of patients in the warfarin group and in 6.9% in the non-warfarin group (p=0.014). Aortic valve area (AVA) did not significantly change in the non-warfarin group during the follow-up, but tended to decrease in the warfarin group (p=0.057). Non-vitamin K antagonist oral anticoagulant got available in Japan after this study started, and warfarin was discontinued in 15 patients of the warfarin group. The reduction of AVA was significant in the remaining 107 patients on the continuous warfarin treatment (p=0.002). The effects of ARB on AVA were obscure. CONCLUSION: Major bleeding associated with VKA is well recognized. This study suggests that the development of aortic valve degeneration is another risk of long-term use of VKA in non-valvular AF patients with no or mild aortic valve degeneration.

Independent predictors of the severity of angiographic coronary atherosclerosis: the lack of association between impaired glucose tolerance and stenosis severity.

Independent predictors of the severity of coronary atherosclerosis are ill defined. We sought to determine the predictors and examine the association of impaired glucose tolerance with stenosis severity. Four hundred thirty-seven patients were studied who underwent coronary angiography for suspected coronary artery disease. Serum concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLc), lipoprotein(a) [Lp(a)] and apolipoproteins (Apo A-I and Apo B) were measured and low-density lipoprotein cholesterol (LDLc) concentration was calculated. Except the patients treated for diabetes mellitus (DM), patients were classified into three groups such as normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and DM by glucose tolerance test. Coronary atherosclerosis index (CAI) representing the severity of coronary atherosclerosis was determined by summation of the stenosis score of all lesions on coronary angiograms. Results indicated that age, total amount of cigarettes smoked, Apo B/Apo A-I, and LDLc/HDLc correlated with CAI, whereas HDLc and Apo A-I concentrations inversely correlated with CAI. TC, TG, Lp(a), LDLc, Apo B concentrations and body mass index did not correlate with CAI. One- and two-hour plasma glucose concentrations and the area of plasma glucose concentration under the curve at the glucose tolerance test did not correlate with CAI, revealing that post-challenge glycemia is not associated with stenosis severity. CAI in IGT patients was significantly lower than that in DM patients but did not differ from that in NGT patients, indicating that IGT does not affect the stenosis severity. Multivariate analysis showed that age, male gender, Apo B/Apo A-I, DM, systemic hypertension, and total amount of cigarettes smoked were independent predictors of CAI.

A new member of MocR/GabR-type PLP-binding regulator of D-alanyl-D-alanine ligase in Brevibacillus brevis.

The Brevibacillus brevis BBR47_28440 gene (referred to as ddlR) encodes an MocR/GabR family transcriptional regulator consisting of an N-terminal helix-turn-helix DNA binding domain and a C-terminal aminotransferase-like domain. The ddlR gene is located just upstream of the d-alanyl-d-alanine ligase gene (ddl) in the B. brevis genome, and these two genes form an operon. Gel-shift assays indicated that purified DdlR binds specifically to the DNA region that includes putative -35 and -10 regions of the ddlR promoter. A 6-bp inverted repeat that overlaps the -10 region of the ddlR promoter was found to be important for the binding. In vivo reporter assays confirmed that DdlR is an activator of the ddlR-ddl operon. Spectroscopic analyses indicated that purified DdlR is a pyridoxal 5'-phosphate binding transcriptional regulator that has dipeptide binding ability for d-alanyl-d-alanine, the enzymatic product of Ddl, and glycylglycine. DdlR is capable of forming a dipeptide-pyridoxal 5'-phosphate external aldimine, but it lacks aminotransferase activity. Bioinformatic analyses suggest that DdlR-mediated transcriptional regulation of ddlR and ddl may occur in multiple bacterial systems such as Actinobacteria and Bacillus species.

Domain characterization of Bacillus subtilis GabR, a pyridoxal 5'-phosphate-dependent transcriptional regulator.

Bacillus subtilis GabR is a transcriptional regulator consisting of a helix-turn-helix N-terminal DNA-binding domain, a pyridoxal 5'-phosphate (PLP)-binding C-terminal domain that has a structure homologous to aminotransferases, and a linker of 29 amino acid residues. In the presence of γ-aminobutyrate (GABA), GabR activates the transcription of gabT and gabD, which encode GABA aminotransferase and succinate semialdehyde dehydrogenase, respectively. We expressed N-terminal and C-terminal domain fragments (named N'-GabR and C'-GabR) in Escherichia coli cells, and obtained N'-GabR as a soluble monomer and C'-GabR as a soluble dimer. Spectroscopic studies suggested that C'-GabR contains PLP and binds to d-Ala, ß-Ala, d-Asn and d-Gln, as well as GABA, although the intact GabR binds only to GABA. N'-GabR does not bind to the DNA fragment containing the GabR-binding sequence regardless of the presence or absence of C'-GabR. A fusion protein consisting of N'-GabR and 2-aminoadipate aminotransferase of Thermus thermophilus bound to the DNA fragment. These results suggested that each domain of GabR could be an independent folding unit. The C-terminal domain provides the N-terminal domain with DNA-binding ability via dimerization. The N-terminal domain controls the ligand specificity of the C-terminal domain. Connection by the linker is indispensable for the mutual interaction of the domains.

Eosinophilic myocarditis without hypereosinophilia accompanied by giant cell infiltration.

A 53-year-old woman with a history of allergic disease was admitted to our hospital because of syncope induced by sustained ventricular tachycardia. The clinical course and the laboratory data did not correspond to those of acute myocarditis. Although eosinophils in the peripheral blood count were not increased, the diagnosis of eosinophilic myocarditis was made following a right ventricular endomyocardial biopsy that showed a remarkable infiltration of eosinophils. While giant cells were another histopathological feature of this case, they were considered to be an expression of the disease severity. This is a rare case of eosinophilic myocarditis, without peripheral eosinophilia. .

Microvascular angina accompanied by epicardial coronary artery spasm.

A case of microvascular angina accompanied by coronary artery spasm is described. A 54-year-old woman had anginal pain at rest and during exercise. Both exercise testing and rapid atrial pacing caused significant ST depression in the inferior and all precordial leads. Exercise thallium myocardial scintigraphy was negative despite similar ST depressions. Coronary angiography revealed insignificant stenoses of the left anterior descending coronary artery after the injection of nitrate. Intracoronary acetylcholine provoked diffuse spasm of the artery with concurrent myocardial lactate production. Coronary flow reserve assessed with papaverine was 2.75. The combined use of amlodipine and high-dose nicorandil was effective for the treatment of angina.

Isolated cardiac sarcoidosis requiring open-chest myocardial biopsy for differentiation from malignant lymphoma.

A 68-year-old woman with a history of hypertension was admitted to our hospital because of dyspnea during physical exertion. Echocardiography demonstrated impaired left ventricular systolic function, and her ejection fraction was reduced to 30%. Coronary angiography did not show significant stenosis. Endomyocardial biopsy showed only nonspecific findings without noncaseating granulomas. Cardiac magnetic resonance (CMR) imaging showed transmural late gadolinium enhancement on the basal part of the left ventricle. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET) showed abnormal focal uptake specific to the left ventricle; no abnormal manifestations in other organs were observed. The CMR and 18F-FDG PET features could not rule out either sarcoidosis or malignant lymphoma. Therefore, we conducted open-chest myocardial biopsy to differentiate between the two possible diseases. Histopathological findings showed noncaseating epithelioid cell granuloma, confirming isolated cardiac sarcoidosis. This is an example of a challenging case of diagnosing isolated cardiac sarcoidosis. .