Association with Right Heart Failure

Abstract A 65-year-old woman, with past history of mitral valve replacement, developed severe right heart failure. In addition to elevated right heart pressure, she had significant hypoalbuminemia as the important cause of refractory edema. Technetium-99m-labelled human serum albumin scintigraphy showed leak of protein from the transverse colon and the excretion of alpha 1 antitrypsin in the stool was markedly increased. Diagnosis of protein losing enteropathy was established. The etiology was increased lymphatic pressure secondary to right heart failure of multifactorial cause, including elevated left side filling pressures and out of proportion pulmonary hypertension due to old tuberculosis, resulting in significant tricuspid regurgitation. The patient was managed conservatively with increased dose of furosemide from 10-20mg every other day up to 40-60mg/day, and maximum dose of tolvaptan (a vasopressin 2 receptor blocker) of 15mg/ day, in addition to high protein diet

The marfan syndrome: Abnormal aortic elastic properties

Aortic distensibility and aortic stiffness index were measured at the ascending aorta (3 cm above the aortic valve) and the mid-portion of the abdominal aorta from the changes in echocardiographic diameters and pulse pressure in 14 patients with the Marfan syndrome and 15 age- and gender-matched normal control subjects. The following formulas were used: 1) Aortic distensibility = 2(Changes in aortic diameter)/(Diastolic aortic diameter) (Pulse pressure); and 2) Aortic stiffness index = ln(Systolic blood pressure)/(Diastolic blood pressure)(Changes in aortic diameter)/Diastolic aortic diameter. Pulse wave velocity was also measured.Compared with normal subjects, patients with the Marfan syndrome had decreased aortic distensibility in the ascending and the abdominal aorta (2.9 ± 1.3 vs. 5.6 ± 1.4 cm2 dynes-1, p < 0.001 and 4.5 ± 2.1, vs. 7.7 ± 2.5, cm2 dynes-1, p < 0.001, respectively) and had an increased aortic stiffness index in the ascending and the abdominal aorta (10.9 ± 5.6 vs. 5.9 ± 2.2, p < 0.005 and 7.1 ± 3.1 vs. 3.9 ± 1.2, p < 0.005, respectively). Aortic diameters in the ascending aorta were larger in these patients than in normal subjects, but those in the abdominal aorta were similar in the two groups. Linear correlations for both aortic distensibility and stiffness index were found between the ascending and the abdominal aorta (r = 0.85 and 0.71, respectively). Pulse wave velocity was more rapid in the patients than in the normal subjects (11.6 ± 2.5 vs. 9.5 ± 1.4 m/s, respectively, p < 0.01).Thus, aortic elastic properties are abnormal in patients with the Marfan syndrome irrespective of the aortic diameter, which suggests an intrinsic abnormality of the aortic arterial wall

RUNX1 transactivates BCR-ABL1 expression in Philadelphia chromosome positive acute lymphoblastic leukemia

The emergence of tyrosine kinase inhibitors as part of a front-line treatment has greatly improved the clinical outcome of the patients with Ph⁺ acute lymphoblastic leukemia (ALL). However, a portion of them still become refractory to the therapy mainly through acquiring mutations in the BCR-ABL1 gene, necessitating a novel strategy to treat tyrosine kinase inhibitor (TKI)-resistant Ph⁺ ALL cases. In this report, we show evidence that RUNX1 transcription factor stringently controls the expression of BCR-ABL1, which can strategically be targeted by our novel RUNX inhibitor, Chb-M'. Through a series of in vitro experiments, we identified that RUNX1 binds to the promoter of BCR and directly transactivates BCR-ABL1 expression in Ph⁺ ALL cell lines. These cells showed significantly reduced expression of BCR-ABL1 with suppressed proliferation upon RUNX1 knockdown. Moreover, treatment with Chb-M' consistently downregulated the expression of BCR-ABL1 in these cells and this drug was highly effective even in an imatinib-resistant Ph⁺ ALL cell line. In good agreement with these findings, forced expression of BCR-ABL1 in these cells conferred relative resistance to Chb-M'. In addition, in vivo experiments with the Ph⁺ ALL patient-derived xenograft cells showed similar results. In summary, targeting RUNX1 therapeutically in Ph⁺ ALL cells may lead to overcoming TKI resistance through the transcriptional regulation of BCR-ABL1. Chb-M' could be a novel drug for patients with TKI-resistant refractory Ph⁺ ALL

Radiolytic one-electron reduction characteristics of tyrosine derivative caged by 2-oxopropyl group

We employed X-irradiation to activate a caged amino acid with a 2-oxoalkyl group. We designed and synthesized tyrosine derivative caged by a 2-oxoalkyl group (Tyr(Oxo)) to evaluate its radiolytic one-electron reduction characteristics in aqueous solution. Upon hypoxic X-irradiation, Tyr(Oxo) released a 2-oxopropyl group to form the corresponding uncaged tyrosine. In addition, radiolysis of dipeptides containing Tyr(Oxo) revealed that the efficiency of radiolytic removal of 2-oxopropyl group increased significantly by the presence of neighboring aromatic amino acids

From the Beam-Envelope Matrix to Synchrotron-Radiation Integrals,” Phys.

The equilibrium state of an electron in a storage ring can be described most accurately by the envelope matrix, as long as the electron motion is hnear. The equilibrium envelope can be calculated in the same way as the equilibrium barycenter (closed orbit). This is suited for accurate numerical calculations. The &quot;emittances&quot; can be extracted from the envelope as approximate quantities. The radiation integrals, which express the emittances in terms of Twiss parameters, dispersions, and other optical parameters, are extended to cover general 6X6 dynamics. Without any coupling between modes, these reduce to those of Sands

Syncope Due to Intracavitary Left Ventricular Obstruction Secondary to Giant Esophageal Hiatus Hernia

Abstract Esophageal hiatus hernia has been known to cause symptoms of congestive heart failure or syncope after meal due to compression of the heart, mainly the left atrium. However, compression of the left ventricle resulting in syncope has never been reported. Seventy-one year old woman developed syncope after taking a lunch. A chest roentgenogram showed possible mass lesion behind the heart. An echocardiogram revealed a mass lesion posterior to the left ventricle, resulting in &quot;banana-shaped&quot; deformity. A CT scan revealed a giant esophageal hiatus hernia which compressed the left ventricle. Cardiac catheterization revealed marked pressure gradient in the left ventricle suggestive of intracavitary obstruction after isoproterenol infusion. Left ventricular compression due to enlarged giant hiatus hernia after meal resulted in intracavitary obstruction of the left ventricle, causing syncopal episode in this particular patient. Dehydration and diastolic dysfunction may also have contributed