Endothelial function measured by peripheral arterial tonometry in patients with chronic myeloid leukemia on tyrosine kinase inhibitor therapy: a pilot study.

BACKGROUND: Arterial occlusive events are an emerging problem in patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) therapy. Endothelial cell damage is thought to play an important role in the development of vascular events. Measurement of the peripheral vasodilator response by peripheral arterial tonometry (PAT) has reportedly been useful in the non-invasive assessment of endothelial dysfunction. To date, no studies have assessed endothelial function using PAT in patients with CML receiving TKIs. METHOD: We measured the reactive hyperemia index (RHI) using PAT in young patients with CML (men aged ≤ 55 years and women aged ≤ 65 years) receiving TKIs. RESULTS: Thirty patients with CML were examined (mean age, 43.5 ± 9.8 years; men, 57%). The median RHI was 1.81. Among these patients, 16.7% and 83.3% were taking imatinib and second- or third-generation TKIs, respectively. There were no differences in the baseline characteristics between the low RHI (< 1.67, n = 10), borderline RHI (≥ 1.67 and < 2.10, n = 14), and normal RHI (≥ 2.10, n = 6) groups. Serum uric acid (UA) levels and the RHI were significantly negatively correlated (r = -0.40, p = 0.029). CONCLUSION: One-third of young patients with CML receiving TKI therapy were classified as having a low RHI. The RHI was negatively correlated with serum UA level. Larger prospective studies are necessary to examine whether the RHI predicts cardiovascular events in such patients.

Atypical Shone's Complex Diagnosed at 70 Years Old: Presenting with Double-orifice Mitral Valve, Bicuspid Aortic Valve, and Aortic Coarctation.

Atypical Shone's complex is a rare congenital anomaly involving a left-sided obstructive lesion of two or three cardiovascular levels. A 70-year-old man with dyspnea on exertion was diagnosed with severe aortic stenosis (AS) with a bicuspid valve, complicated by severe aortic coarctation (CoA) and a double-orifice mitral valve. He underwent surgery for AS and CoA in one session. It is important to search for complicated malformations, even in cases of bicuspid aortic valve found in old age.

Effectiveness of real-time tele-ultrasound for echocardiography in resource-limited medical teams.

BACKGROUND: Echocardiography is a first-line tool for the screening of patients with cardiac dysfunction. However, the mastery of echocardiography requires significant training, and not all medical teams involve an echocardiography specialist. Telemedicine approaches can potentially improve the quality of echocardiography in resource-limited situations. METHODS: We used a novel tablet-based hand-held ultrasound device that enables tele-ultrasound- a real-time video telecommunication with remote control for ultrasound images. A trainee scanned patients with various cardiovascular diseases and interpreted the images. Subsequently, the same trainee re-scanned the same patients and re-interpreted the same images using tele-ultrasound with an echocardiography specialist. An examination on the same patients by a blinded specialist was considered the gold standard. RESULTS: We included 31 patients (median 77 [interquartile range 68-84] years old, 42% women). Mean absolute errors in left ventricular (LV) end-diastolic and end-systolic diameters, visual LV ejection fraction, and tricuspid annular plane systolic excursion decreased significantly after tele-ultrasound advice (5.9 mm, 5.8 mm, 8.6%, and 4.5 to 1.6 mm, 2.8 mm, 0.7%, and 1.8 mm, respectively, all p < 0.001), and intra-class correlation coefficients improved (0.76, 0.84, 0.68, and 0.44 to 0.96, 0.93, 0.99, and 0.90, respectively). Notably, with tele-advice, the trainee's examination showed perfect agreement with that of the specialist in classifying LV ejection fraction (> 50%, 50-35%, or > 35%) and identifying significant valvular heart diseases. CONCLUSION: Real-time tele-ultrasound improved a trainee's echocardiography results to those of a specialist-level examination. This approach might be helpful in resource-limited medical teams where echocardiographic specialists are not readily available.

Myocardial triglyceride content in patients with left ventricular hypertrophy: comparison between hypertensive heart disease and hypertrophic cardiomyopathy.

Proton magnetic resonance spectroscopy (1H-MRS) enables the assessment of myocardial triglyceride (TG) content, which is reported to be associated with cardiac dysfunction and morphology accompanied by metabolic disorder and cardiac hemodynamic status. The clinical usefulness of myocardial TG content measurements in patients with left ventricular hypertrophy (LVH) has not been fully investigated. We examined whether myocardial TG content assessed by 1H-MRS was useful for diagnosis in patients with LVH. To quantify myocardial TG content, we conducted 1H-MRS in 35 subjects with LVH. Left ventricular function was measured by cardiac magnetic resonance imaging. Patients were assigned to a hypertensive heart disease (HHD, n = 10) or hypertrophic cardiomyopathy (HCM, n = 25) group based on the histology and/or late gadolinium enhancement pattern. The myocardial TG content was significantly higher in the HHD group than in the HCM group (2.14 ± 1.29 vs. 1.09 ± 0.72 %, P < 0.001). Myocardial TG content were significantly and negatively correlated with LV mass (r = -0.41, P < 0.04) and stroke volume (r = -0.64, P < 0.05) in the HCM group and HHD group, respectively. In a multivariate analysis, LV mass volume and diagnosis of HCM or HHD were independent factors of the myocardial TG content. The results suggest that myocardial metabolism may differ between HCM and HHD patients and that measurement of myocardial TG content by 1H-MRS may be useful for evaluating the myocardial metabolic features of LVH.

Implications of an inverted duplication in the wheat KN1-type homeobox gene Wknox1 for theorigin of Persian wheat.

Introgression between related species with different ploidy levels has played important roles in wheat subspecies differentiation. Persian wheat, a cultivated tetraploid wheat subspecies (Triticum turgidum subsp. carthlicum), is postulated to have evolved through interploidy hybridization between tetraploid and hexaploid wheats. Here, we report evidence for the origin of subsp. carthlicum based on the discovery of a new allele for the 5th-to-6th exon region of the Wknox1bKNOTTED1-type homeobox gene in a common wheat subspecies (T. aestivum subsp. carthlicoides). In this Wknox1b region, subsp. carthlicoides contains an inverted duplication mutation in the 3' flanking region of a 157-bp MITE insertion site. This structural mutation resulted in the suppression of Wknox1b expression in subsp. carthlicoides, but no structural mutation was observed in the same region of subsp. carthlicum. In addition, the carthlicum allele for the Wknox1b 5th-to-6th exon region exhibited the same sequence as that in the wild emmer wheat subsp. dicoccoides. These observations support an alternative hypothesis that subsp. carthlicum evolved by interploidy hybridization between subsp. carthlicoides and tetraploid wheat.

Childhood-Onset Anti-Ku Antibody-Positive Generalized Morphea with Polymyositis: A Japanese Case Study.

We report a 16-year-old Japanese girl with anti-Ku antibody-positive generalized morphea and polymyositis who, at the age of 7 years, developed multiple brownish plaques on her left forearm that gradually extended to her upper arm, back, and left thigh, which a skin biopsy revealed as morphea. Laboratory testing was positive for antinuclear antibody and a high serum creatine kinase level. Although there were no clinical signs of muscular involvement, magnetic resonance imaging revealed findings consistent with myositis. The patient is one of the youngest reported cases positive for anti-Ku antibody. Anti-Ku positivity concomitant with generalized morphea is rare.

Functional conservation of wheat orthologs of maize rough sheath1 and rough sheath2 genes.

Maize rough sheath2 (RS2) and Arabidopsis ASYMMETRIC LEAVES1 (AS1) both encode a Myb transcription factor and repress Knotted1-type homeobox (KNOX) genes. The RS2/AS1-KNOX relationship is functionally conserved between maize and Arabidopsis. Here, we cloned wheat orthologs of RS2/AS1 and of a maize rough sheath1 (rs1) KNOX gene and named them WRS2 and WRS1, respectively. WRS1 mRNA was detected at leaf insertion points of the vegetative shoot meristem but was missing in differentiating floral organs. Conversely, WRS2 transcripts accumulated in initiating and developing floral organs. Transgenic tobacco plants expressing WRS1 showed morphological alterations typically observed due to expression of other KNOX genes. WRS2 with a deletion of the Myb domain could interact with NtPHAN to form a heterodimer, and expression of the truncated WRS2 gene conferred a dominant-negative phenotype similar to that expected and induced ectopic expression of an endogenous KNOX gene. Moreover, WRS2 expression alleviated morphological alterations in tobacco plants expressing the wheat KNOX gene. Therefore, the WRS2 gene product represses KNOX expression. These results indicate that the WRS2-KNOX relationship plays a fundamentally important role in lateral organ initiation and differentiation of meristems in wheat development. The antagonistic relationship between WRS2 and KNOX around meristematic tissues has been functionally conserved during wheat evolution.

Intragenic diversity and functional conservation of the three homoeologous loci of the KN1-type homeobox gene Wknox1 in common wheat.

Common wheat represents a typical allohexaploid species and provides a good experimental system for studying genomic alterations associated with allopolyploidization. We studied three homoeologous loci of wheat Wknox1 gene, which is highly homologous to the knotted1 (kn1)-like homeobox (KNOX) genes functioning at shoot apical meristems (SAM). Wknox1 transcripts were detected in SAM, and its overexpression caused abnormal leaf morphology with occasional ectopic leaves in transgenic tobacco plants. A comparative study of the three Wknox1 genomic sequences revealed accumulation of a large number of mutations including insertions and deletions, particularly in the fourth intron and the 5'-upstream region. Some structural mutations including MITE-insertions were allocated in the evolutionary lineage of the wheat genome, suggesting that they occurred at all stages of wheat evolution. A mutation rate was the highest in the Wknox1b locus, which is consistent with the known highest degree of differentiation in the B genome. Despite the structural differentiation, all three Wknox1 homoeologs showed an identical expression pattern in wheat and their promoter regions induced the conserved expression pattern in transgenic tobacco plants. A potential of the intragenic diversity in homoeologs of essential genes as a tool for studying the genome evolution associated with allopolyploidization was discussed.