A Case of Cardiac Amyloidosis Presenting with Mid- to Late Diastolic Retrograde Flow from the Left Atrium to the Pulmonary Vein: Transesophageal Pulsed Doppler Echocardiographic Observations

A patient of cardiac amyloidosis was found to have mid-to late diastolic retrograde flow from the left atrium (LA) to the pulmonary vein. Congo-red staining was positive for amyloid in the rectal tissue. M-mode and two-dimensional echocardiograms revealed symmetric hypertrophy and typical speckled pattern of the left ventricle (LV). The LV pressure curve showed a dip and plateau configuration during diastole, and end-diastolic pressure was 28 mmHg. In addition, the LV pressure was high at mid-diastole, surpassing the pulmonary capillary wedge pressure from mid-to late diastole. The transmitral flow velocity revealed "restrictive" pattern, and the pulmonary venous flow velocity showed retrograde flow from the LA to the pulmonary vein during mid-diastole and atrial systole. It is suggested that recording of the pulmonary venous flow velocity by transesophageal pulsed Doppler echocardiography is useful for understanding the mechanism of the development of pulmonary congestion or edema.     

Local neurohumoral regulation in the transition to isolated diastolic heart failure in hypertensive heart disease: absence of AT1 receptor downregulation and 'overdrive' of the endothelin system

OBJECTIVE: Although isolated diastolic heart failure with preserved left ventricular (LV) systolic function frequently occurs, regulation of local neurohumoral factors in the transition from diastolic dysfunction without signs of heart failure to diastolic failure, a target for therapeutic strategy, remains to be clarified, partly because of a lack of animal models. Our laboratory recently demonstrated that Dahl-Iwai salt-sensitive (Dahl-S) rats fed on a high-salt diet since 7 weeks of age develop hypertension followed by compensated LV hypertrophy at 13 weeks and transition to isolated diastolic heart failure at 19 weeks. METHODS: Gene expression of the components of the renin-angiotensin system, endothelin (ET) system and natriuretic peptide system in the left ventricle was investigated in the transition to isolated diastolic heart failure in this model. RESULTS: The compensated ventricular hypertrophy was associated with slight increases in angiotensin-converting enzyme (ACE) and angiotensin II type-1a (AT1a) receptor mRNA levels. Although preproET-1 (ppET-1) and ET-converting enzyme-1 (ECE-1) mRNA levels were not increased, mRNA levels of ET type-A (ETA) and ET type-B (ETB) receptors were increased. Atrial natriuretic peptide (ANP) mRNA level increased, but not brain natriuretic peptide (BNP) mRNA level. At the decompensated failing stage (at 19 weeks), ACE mRNA level further increased without downregulation of ATla receptor mRNA level. The mRNA levels of ppET-1 and ECE-1 increased with persistent upregulation of mRNA levels of ETA and ETB receptors, and immunohistochemical staining for ET-1 was found at endothelial cells and myocytes. BNP mRNA level increased with a further increase in ANP mRNA level. CONCLUSIONS: The transition to isolated diastolic heart failure in hypertrophied hearts was associated with preserved gene expression of the renin-angiotensin system and 'overdrive' of gene expression of the ET system. BNP gene expression is likely to be activated by the progression of diastolic failure rather than by LV hypertrophy alone.     

Generation of a large number of functional dendritic cells from human monocytes expanded by forced expression of cMYC plus BMI1

Anticancer vaccination therapies with monocyte-derived dendritic cells (DC) are widely conducted. A large number of primary monocytes (approximately 10⁸ cells) are needed to generate the number of DC required to achieve an effect upon vaccination, and monocytes are usually purified from peripheral blood mononuclear cells obtained by apheresis procedure, which is somehow invasive for cancer patients. As a means to facilitate the generation of DC for therapeutic use, we herein report a method to amplify human monocytes. We found that lentivirus-mediated transduction of cMYC along with BMI1 induced proliferation of CD14⁺ monocytes derived from 9 out of 12 blood donors, and we named the monocyte-derived proliferating cells CD14-ML. Their proliferation continued for 3–5 weeks in the presence of M-CSF and GM-CSF, resulting in 20–1000-fold amplification. Importantly, the expanded CD14-ML differentiated into fully functional DC (CD14-ML-DC) upon the addition of IL-4 to the culture. We successfully stimulated autologous CD8⁺ T cells with CD14-ML-DC pulsed with cytomegalovirus peptide or MART-1 peptide to generate antigen-specific CTL lines. This is the first report describing the method for in vitro expansion of human peripheral blood monocytes.     

Vascular evaluation using transabdominal ultrasound for gallbladder polyps

Journal of Medical Ultrasonics - Ultrasound (US) is a cost-effective and noninvasive procedure without radiation exposure, with real-time evaluation and high spatial resolution. Although it is...     

Induction of islet B-cell regeneration in partially pancreatectomized rats by poly(ADP-ribose) synthetase inhibitors

In order to clarify the mechanism of the prevention of diabetes mellitus developing after subtotal pancreatectomy, we examined regenerative activities of islet B-cells in 90% pancreatectomized and poly (ADP-ribose) synthetase inhibitor-treated rats by using autoradiographic and stathmokinetic techniques. Thirty days after 90% pancreatectomy, islets of rats without 3-aminobenzamide treatment were decreased in number, small in size and had irregular contour. Degranulation of the B-cells and fibrotic degeneration were frequently encountered. On the contrary, islets of remaining pancreas in rats receiving 3-aminobenzamide were increased in number, and their diameters ranged from 0.3-0.6 mm, being about two fold larger than those of normal rats. The labeling index of 3H-thymidine autoradiography and the mitotic indices in islet B-cells were increased in a temporally correlated manner in the 3-aminobenzamide treated rats. The mitotic indices of the 3-aminobenzamide-treated group on the 5th, 7th, 10th and 15th days were significantly larger than those in the control group. These results indicate that poly (ADP-ribose) synthetase inhibitors can induce self-replication or regeneration of B-cells in partially pancreatectomized rats.     

Photoinducible phase-specific light induction of Cry1 gene in the pars tuberalis of Japanese quail

Prolactin (PRL) secretion is regulated by photoperiod in mammals and birds. In mammals, the pars tuberalis (PT) in the pituitary is involved in the regulation of photoperiodic regulation of PRL secretion. In birds, however, hypothalamic vasoactive intestinal peptide is implicated in PRL secretion, and physiological roles of the avian PT remain unknown. In the present study, we show that PRL secretion increases under long days and short days with a night interruptive schedule, both of which also cause gonadal growth in Japanese quail. We have also found Cry1 gene expression in the PT of Japanese quail. Cry1 expression was rhythmic under long and short photoperiods in the PT, and the peak was phase delayed under a lengthened photoperiod. Moreover, expression of Cry1 gene was induced by a light pulse but only when given during the photoinducible phase. In our previous study, we have shown rhythmic Per2 gene expression with a peak in the PT during the early day under various photoperiods. When taken together with the results from the present study, different phase relationships between Per2 and Cry1 in the Japanese quail PT under different photoperiods may decode photoperiodic information and regulate photoperiodic PRL secretion in a manner similar to that of mammals.