Influence of oxytetracycline susceptibility as a first-line antibiotic on the clinical outcome in dairy cattle with acute Escherichia coli mastitis.

The purpose of this study was to clarify the therapeutic effects of oxytetracycline (OTC) as a first-line antibiotic in cattle with acute Escherichia coli mastitis and systemic signs. Drug susceptibility was determined by the minimum inhibitory concentration (MIC) of E. coli isolated from cows with acute E. coli mastitis (n=38). Cattle were divided into OTC-susceptible (S, n=30) and OTC-resistant (R, n=8) groups. They were further subdivided according to susceptibility to the antibiotic used as a second treatment, into susceptible-susceptible (SS, n=30), resistant-susceptible (RS, n=5), and resistant-resistant (RR, n=3) groups. Clinical signs on the day after initial treatment were compared between S and R groups as short-term indicators of treatment effects. The 28-day survival rate of cattle was then compared among SS, RS, and RR groups as a long-term indicator of treatment effects. There were no differences in clinical signs between S and R groups on the day after the first dose, but the 28-day survival rate was significantly greater in the SS group than in the RR group (P=0.04). The results demonstrated that an effective drug is essential for first-line treatment of acute coliform mastitis. However, anticipating the effectiveness of a first-line antibiotic based on clinical symptoms at the second day of treatment is impossible. It is important to build a picture of drug resistance trends in cattle herds for empirical selection of antibiotics to be administered.

Gender differences in the clinical characteristics and outcomes of patients with vasospastic angina--a report from the Japanese Coronary Spasm Association.

BACKGROUND: Accumulating evidence has demonstrated the gender differences in the clinical characteristics and outcomes of patients with ischemic heart disease. However, it remains to be elucidated whether it is also the case for vasospastic angina (VSA). METHODS AND RESULTS: We enrolled a total of 1,429 VSA patients (male/female, 1090/339; median age 66 years) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. As compared with male patients, female patients were characterized by older age (median 69 vs. 66 years), lower incidence of smoking (20% vs. 72%) and less significant organic stenosis (9% vs. 16%) (all P=0.001). Multivariate analysis demonstrated that the predictors of major adverse cardiac events (MACE) were considerably different by genders; women were more associated with age and electrical abnormalities, whereas men with structural abnormalities. Overall 5-year MACE-free survival was comparable between both genders. However, when the patients were divided into 3 groups by age [young (<50 years), middle-aged (50-64 years) and elderly (≥65 years)], the survival was significantly lower in the young female group (young 82%, middle-aged 92%, elderly 96%, P<0.01), where a significant interaction was noted between age and smoking. In contrast, the survival was comparable among the 3 age groups of male patients. CONCLUSIONS: These results indicate that there are gender differences in the characteristics and outcomes of VSA patients, suggesting the importance of gender-specific management of the disorder.

Delayed enhancement on cardiac magnetic resonance imaging is a poor prognostic factor in patients with cardiac sarcoidosis.

BACKGROUND: Predictors of ventricular arrhythmias (VA) in patients with cardiac sarcoidosis (CS) remain unclear. METHODS AND RESULTS: We examined 61 consecutive CS patients who were admitted to our hospital from April 2002 to March 2012 with a mean follow-up period of 45 ± 31 months for the relationship between delayed enhancement on cardiac magnetic resonance imaging (DE-MRI) and VA or a composite endpoint, including VA, heart failure hospitalization, and cardiovascular mortality. Although there was no significant difference in baseline clinical characteristics between patients with VA and those without it, the former group was characterized as compared with the latter by lower left ventricular (LV) ejection fraction (p<0.05), larger LV systolic/diastolic dimensions (both p<0.05), and a significant association with DE-MRI (p<0.05). Furthermore, the patients with DE-MRI (n=26), as compared with those without it (n=11), had a significantly higher composite endpoint event rate (41% vs. 0%, p<0.05) and a trend toward higher VA (29% vs. 0%, p=0.12). Univariate analysis also showed that impaired LV systolic function was significantly associated with composite events on follow-up. CONCLUSIONS: These results indicate that the presence of DE-MRI is a significant predictor of VA events and poor outcome in CS patients.

Increased incidence of tachyarrhythmias and heart failure hospitalization in patients with implanted cardiac devices after the great East Japan earthquake disaster.

BACKGROUND: After the East Japan Earthquake disaster there may have been a deterioration of patients with cardiovascular diseases. METHODS AND RESULTS: We examined the data from 189 consecutive patients implanted with cardiovascular devices for the 6-month period before and after the Earthquake. In 170 patients with defibrillators, the number who experienced tachyarrhythmias increased significantly after the Earthquake (28 ± 5 vs. 34 ± 3 patients/month, P<0.05). In 74 patients with biventricular pacemakers, the number of heart failure hospitalizations significantly increased after the Earthquake (1.2 ± 1.0 vs. 2.7 ± 1.2 patients/month, P<0.05). CONCLUSIONS: The East Japan Earthquake disaster unfavorably affected patients implanted with defibrillators or biventricular pacemakers.

Primary aldosteronism with right-dominant heart failure.

A 48 year-old obese male with hypertension was admitted to our department because of severe right-dominant heart failure. His heart rhythm was 2:1 atrial flutter and the left ventricle was diffusely hypertrophic and hypokinetic. Primary aldosteronism was diagnosed based on severe hypokalemia (2.6 mEq/L) and a low renin-high aldosterone state with hypertension despite the use of an angiotensin-II receptor blocker, but its etiology could not be clarified with computed tomography, adrenal scintigraphy, and adrenal vein sampling. Ascites and edema rapidly worsened. Ascites aspiration was performed daily, until serum potassium was normalized by a full dose of an aldosterone receptor blocker (spironolactone 100 mg/day). A diuretic (furosemide) was then added. Rate control of atrial flutter was obtained with a beta-adrenergic blocker, and anticoagulation therapy was started. His heart failure was successfully controlled. Coronary arteries were normal on coronary arteriograms, and an endomyocardial biopsy sample obtained from the left ventricle did not show any specific pathological findings. Blood pressure was well controlled with the full dose of the aldosterone receptor blocker, but he died one year later due to intracerebral hemorrhage. As his heart failure was right dominant, we believe that its etiology may have been hyperaldosteronism-induced cardiomyopathy, and not advanced hypertensive heart disease.

Involvement of the N-terminal unique domain of Chk tyrosine kinase in Chk-induced tyrosine phosphorylation in the nucleus.

Chk tyrosine kinase phosphorylates Src-family kinases and suppresses their kinase activity. We recently showed that Chk localizes to the nucleus as well as the cytoplasm and inhibits cell proliferation. In this study, we explored the role of the N-terminal unique domain of Chk in nuclear localization and Chk-induced tyrosine phosphorylation in the nucleus. In situ binding experiments showed that the N-terminal domain of Chk was associated with the nucleus and the nuclear matrix. The presence of the N-terminal domain of Chk led to a fourfold increase in cell population exhibiting Chk-induced tyrosine phosphorylation in the nucleus. Expression of Chk but not kinase-deficient Chk induced tyrosine phosphorylation of a variety of proteins ranging from 23 kDa to approximately 200 kDa, especially in Triton X-100-insoluble fraction that included chromatin and the nuclear matrix. Intriguingly, in situ subnuclear fractionations revealed that Chk induced tyrosine phosphorylation of proteins that were associated with the nuclear matrix. These results suggest that various unidentified substrates of Chk, besides Src-family kinases, may be present in the nucleus. Thus, our findings indicate that the importance of the N-terminal domain to Chk-induced tyrosine phosphorylation in the nucleus, implicating that these nuclear tyrosine-phosphorylated proteins may contribute to inhibition of cell proliferation.

Adaptor protein Crk is required for ephrin-B1-induced membrane ruffling and focal complex assembly of human aortic endothelial cells.

Endothelial cell migration is an essential step in vasculogenesis and angiogenesis, in which receptor tyrosine kinases play a pivotal role. We investigated the mechanism by which ephrin-B1 promotes membrane ruffling in human aortic endothelial cells, because membrane ruffling heralds cell body migration. We especially focused on the role of Crk adaptor protein in EphB-mediated signaling. Using DsRed-tagged Crk and a fluorescent time-lapse microscope, we showed that Crk was recruited to the nascent focal complex after ephrin-B1 stimulation. Furthermore, we found that p130(Cas), but not paxillin, recruited Crk to the nascent focal complex. The necessity of Crk in ephrin-B1-induced membrane ruffling was shown both by the overexpression of dominant negative Crk mutants and by the depletion of Crk by using RNA interference. Then, we examined the role of two major downstream molecules of Crk, Rac1 and Rap1. The dominant negative mutant of Rac1 completely inhibited ephrin-B1-induced membrane ruffling and focal complex assembly. In contrast, rap1GAPII, a negative regulator of Rap1, did not inhibit ephrin-B1-induced membrane ruffling. However, in rap1GAPII-expressing cells, ephrin-B1 did not induce membrane spreading, probably due to instability of the focal complex. These results indicated that Crk plays a critical role in Rac1-induced membrane ruffling and Rap1-mediated nascent focal complex stabilization contributing to ephrin-B1-induced human aortic endothelial cells migration.