Rate-dependent changes in atrial action potential duration after short- duration rapid atrial pacing in humans.

The effect of rapid atrial pacing on the rate adaptation of the atrial action potential duration was studied in humans. The right atrial monophasic action potential (RAMAP) of 5 patients was recorded before and after 30 min of rapid atrial pacing. The pacing cycle length (CL) was 146 +/- 9 ms, the shortest duration at which 1:1 capture was possible. The RAMAP duration at 90% repolarization (RMAPD) was measured. CL-dependent changes in RAMAPD (CL 600 ms-CL 300 ms) before and after rapid atrial pacing were 51.8 +/- 10.7 ms and 30.8 +/- 7.6 ms (p < 0.05), respectively.     

Growth mechanism of human myeloma cells by interleukin-6

Human myeloma cells are heterogenous morphologically and phenotypically. Myeloma cells can be classified into at least 5 subpopulations; MPC-1-CD45+CD49e-, MPC-1-CD45-CD49e- immature myeloma cells, MPC-1+CD45-CD49e-, MPC-1+CD45+CD49e- intermediate myeloma cells and MPC-1+CD45+CD49e+ mature myeloma cells. Interleukin-6(IL-6) is a major growth factor for human myeloma cells, but only MPC-1-CD45+CD49e- immature myeloma cells can response directly to IL-6 to proliferate. In the U-266 cell lines, IL-6 can lead to the induction of CD45 expression and CD45+ U-266 cells can proliferate in response to IL-6. In primary myeloma cells, MPC-1-CD45-CD49e- immature myeloma cells sorted from bone marrow samples can be changed to CD45+ cells by addition of IL-6 in vitro. In both CD45- and CD45+ U-266 cells, STAT3 and MAPK(ERK1/2) can be activated in response to IL-6 equally between them, but src family kinases such as Lyn, Fyn can be activated only in CD45+ U-266 cells. Thus, the activation of the src family kinases associated with CD45 expression is a prerequisite for the proliferation of myeloma cells. In the bone marrow of myeloma patients, most myeloma cells do not express CD45, and CD45+ immature myeloma cells are only 1 approximately 2%. In order to clarify the difference of cellular context between CD45- and CD45+ myeloma cells, PCR-based cDNA subtraction was performed from CD45+ U-266 cells to CD45-U-266 cells. The series of this subtraction selected several genes. Furthermore, sensitivity to stress stimuli between CD45+ and CD45- U-266 cells was also compared. CD45-U-266 cells were markedly more resistant to stress conditions such as serum-free condition. Therefore, we can speculate that in the bone marrow of human myelomas IL-6 can induce proliferation of CD45+ immature cells, but the amount of IL-6 is too low to support CD45+ myeloma cells and loss of CD45 results in no direct response to IL-6 to proliferate but confers resistance to stress condition leading to the longer survival at the limited amount of IL-6.     

Autonomic responses to orthostatic stress in head-up tilt testing: Relationship to test-induced prolonged asystole

Background: Prolonged asystole is sometimes an extreme manifestation of neurally mediated syncope. Hypothesis: To investigate the mechanism of head-up tilt testing-induced prolonged (life-threatening) cardiac asystole, we measured temporal changes in frequency domain heart rate variability indices in 25 patients with syncope of undetermined etiology. Methods: Head-up tilt testing (80°) was performed in 25 patients for up to 40 min or until asystole or syncope occurred. Three patients (Group 1; 37 ±13 years, 1 man, 2 women) had an episode of prolonged cardiac asystole (≥ 10 s) during testing, necessitating cardiopulmonary resuscitation. Syncope, but no asystole, was induced in 10 patients (Group 2; 48 ± 31 years, 6 men, 4 women), and 12 patients (Group 3; 55 ± 20 years, 5 men, 7 women) failed to show asystole or syncope during testing. Power spectra of low (0.04–0.15 Hz) and high (0.15–0.40 Hz) frequency, and total (0.01–1.00 Hz) frequency spectra were measured in consecutive 2 min segments throughout the test. Results: Maximally changed values in heart rate, systolic blood pressure, and heart rate variability indices during testing were compared among the three groups (maximally changed values did not include the values during tilt-induced symptoms). High frequency spectra in Groups 2 and 3, but not in Group 1, decreased during the test. High frequency spectra, low frequency spectra, and total spectra in Group 1 were significantly higher than those in Groups 2 and 3 during testing. In Group 1 patients, findings at test-induced asystole were consistent with exaggerated sympathetic and concurrent persistent parasympathetic activity. Conclusion: Unusual autonomic responses to orthostatic stress can cause prolonged asystole, and this autonomic nerve dysregulation may relate to asystolic episodes associated with cardiovascular collapse.     

Quantitative Monitoring of Circulating Epstein-Barr Virus DNA for Predicting the Development of Posttransplantation Lymphoproliferative Disease

Epstein-Barr virus (EBV)-DNA was quantitatively measured to assess posttransplantation virus reactivation by real-time polymerase chain reaction (PCR). In the first retrospective analysis of a 7-year-old boy with lymphoproliferative disease (LPD) after an unrelated cord blood transplantation, serum EBV-DNA progressively increased to 4 x 10(5) copies/mL. EBV load was then prospectively monitored in peripheral blood from posttransplantation patients. The second case was an 8 year-old boy with aplastic anemia who received a CD34+ cell transplantation. This patient died of LPD with the progression of pulmonary nodules. EBV-DNA increased to 4 x 10(4) copies/mL after the control of cytomegalovirus reactivation. On the other hand, EBV-DNA was undetectable (<200 copies/mL) in the series of all 58 samples from 10 patients who did not develop LPD after hematopoietic stem cell transplantation. Sequential monitoring of circulating EBV-DNA by quantitative PCR may be a useful indicator for predicting the development of posttransplantation LPD.     

Serum Total Cholesterol Levels Would Predict Nosocomial Infections After Gastrointestinal Surgery

It has been suggested that total cholesterol levels and the use of statin medications are associated with the incidence of complications after gastrointestinal surgery. The aim of this study was to determine if preoperative total cholesterol levels are associated with a higher risk of postoperative infections and mortality. A total of 2211 patients undergoing general surgical procedures between December 2006 and November 2008 at Iizuka Hospital and between January 2010 and March 2012 at Jichi Medical University Hospital were reviewed. Multiple logistic regression models were used to evaluate serum total cholesterol and other variables as predictors of postoperative nosocomial infections. Serum total cholesterol concentrations lower than 160 mg/dl were associated with an increased incidence of superficial and deep incisional surgical site infections. Serum total cholesterol levels showed a reverse J-shaped relationship with the development of organ space surgical site infection and pneumonia. There was no discernible effect of serum cholesterol levels on the postoperative mortality observed in this cohort of patients. Decreased serum albumin was one of the strongest risk factors for the development of nosocomial infection after surgery. Postoperative pneumonia was not observed in patients taking statin medications whose cholesterol levels were <200 mg/dl. Serum total cholesterol may be a valid predictor of surgical outcome. Preoperative statin use may affect the development of postoperative pneumonia in patients with total cholesterol levels below 200 mg/dl.     

Noninvasive diagnosis of dual AV nodal physiology in patients with AV nodal reentrant tachycardia by adenosine triphosphate test

Atrioventricular nodal reentrant tachycardia (AVNRT) is a relatively common paroxysmal supraventricular tachycardia. This study investigated whether adenosine-5'-triphosphate (ATP) injection during sinus rhythm might be useful in the noninvasive diagnosis of dual AV nodal pathways. The study group consisted of 9 patients with slow/fast AVNRT and 11 control patients without antegrade dual AV nodal physiology (DAVNP). ATP (2.5 to 30 mg, in 2.5-mg increments was injected during sinus rhythm until signs of DAVNP (> or = 50 msec increase or decrease in AH or PR interval in two consecutive beats) or > or = second-degree AV block was observed. DAVNP was diagnosed by ATP test in all 9 patients with slow/fast AVNRT. DAVNP was observed by ATP test in 3 of the 11 control patients. Thus, the test had a sensitivity of 100% and specificity of 73%. ATP test given during sinus rhythm is useful for identifying patients with dual AV nodal pathways who are prone to AVNRT.     

Genetically engineered rice resistant to rice stripe virus, an insect-transmitted virus.

The coat protein (CP) gene of rice stripe virus was introduced into two japonica varieties of rice by electroporation of protoplasts. The resultant transgenic plants expressed the CP at high levels (up to 0.5% of total soluble protein) and exhibited a significant level of resistance to virus infection. Plants derived from selfed progeny of the primary transformants also expressed the CP and showed viral resistance, indicating stable transmission of the CP gene and the trait of resistance to the next generation. Moreover, the virally encoded strip disease-specific protein was not detected in transgenic plants expressing CP 8 weeks after inoculation, indicating protection before viral multiplication. These studies demonstrated that CP-mediated resistance to virus infection can be extended to cereals and to the viruses transmitted by an insect vector (planthopper).     

Improvement in physiological outcomes and health-related quality of life following cardiac rehabilitation in patients with acute myocardial infarction.

BACKGROUND: The present study examined the impact of an 8-week cardiac rehabilitation (CR) program on physiological outcomes and health-related quality of life (HRQOL) of patients with acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 124 consecutive AMI patients were divided into a supervised outpatient CR group (n=82) and a non-CR group as a control (n=42). Peak oxygen uptake, handgrip strength, and knee extension muscular strength were used as physiological outcome measures. HRQOL outcomes were assessed by the Medical Outcome Study Short Form 36 (SF-36). CR group patients performed both aerobic exercise and moderate resistance training from 1 month (T1) to 3 months (T2) after AMI onset. Age, sex, body mass index, medications, and ejection fraction were similar in both groups. Significantly greater increases in overall physiological outcomes from T1 to T2 were measured in the CR group compared with those of the non-CR group. There were also significantly greater improvements in 4 of the 8 SF-36 health status subscales (physical functioning, role-physical, general health, and vitality) in the CR group compared with the non-CR group. CONCLUSIONS: Eight weeks of exercise training have specific effects on improvement in HRQOL and physiological outcomes in Japanese patients.     

Prediction of genetic risk for hypertension

BACKGROUND: Although genetic epidemiological studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. Large-scale association studies that examine many gene polymorphisms simultaneously are required to predict genetic risk for hypertension. METHODS and RESULTS: The population of the present study comprised 1,940 unrelated Japanese individuals, including 1,067 subjects with hypertension (574 men, 493 women) and 873 controls (533 men, 340 women). The genotypes for 33 single nucleotide polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, diabetes mellitus, hypercholesterolemia, and hyperuricemia revealed that two polymorphisms (825C -> T in the G protein beta3 subunit gene and 190G -> A in the CC chemokine receptor 2 gene) were significantly associated with hypertension in men and that one polymorphism (-238G -> A in the tumor necrosis factor- alpha gene) was significantly associated with hypertension in women. CONCLUSION: These results suggest that two and one genes may be susceptibility loci for hypertension in Japanese men and women, respectively, and that genotyping of these polymorphisms may prove informative for prediction of the genetic risk for hypertension.