Asynchronous filling in ischemic heart disease and hypertrophic cardiomyopathy

A multigated blood-pool study was performed to assess regional and global emptying and filling in 16 patients with hypertrophic cardiomyopathy (HCM), 43 patients with ischemic heart disease (IHD), and 14 controls. The regional volume curve was fitted using second-order harmonics in the Fourier series, while the global left-ventricular volume curve was fitted using third-order harmonics. As asynchronous indices, the standard deviations (SD) in distribution histograms of time to end-systole (TES), time to peak ejection (TPE), and time to peak filling (TPF) were obtained in the left ventricle. In patients with IHD, the TPF-SD was higher (14.4±11.3°) than the TES-SD (7.8±5.1°) and TPE-SD (8.1±5.9°), suggesting the presence of asynchronous filling. In patients with HCM, the TPF-SD was also higher (11.6±11.1°) than the TES-SD (3.5±2.4°) and TPE-SD (6.2±4.4°). The phase delay was localized in the anteroseptal or apical region in all 5 HCM patients with abnormal wall motion, while it corresponded with the region of abnormal wall motion in the patients with IHD. The TPF-SD was inversely correlated with the left-ventricular ejection fraction (r=-0.46), peak filling rate (r=-0.50), and the ratio of peak filling rate to peak ejection rate (r=-0.52), suggesting that asynchronous filling is related to global diastolic disturbance. We conclude that asynchronous filling is often present in patients with IHD and HCM, and that our technique can be used to obtain a quantitative assessment of regional asynchronous emptying and filling in these diseases.     

The discrepancy between immunocytochemical and biochemical assay of estrogen receptor in breast cancer patients treated by endocrine therapy

Estrogen receptor (ER) expression was investigated by ER-immunocytochemical assay (ICA) and the dextran coated charcoal (DCC) method in 10 recurrent or primary-advanced breast cancer patients treated with endocrine or chmmo-endocrine therapy. In 6 of these 10 patients, ER was examined both before and after treatments by the 2 methods. ER contents measured by the DCC method were found to be decreased after treatments, however, no change in the immunoreactivities of ER-ICA was observed. In the remaining 4 patients, the ER of new lesions refractory to endocrine or chemo-endocrine therapy was examined. ER status was determined as negative in 3 of the 4 patients by the DCC method, whereas by ER-ICA, the proportion of ER stained cells was about 70 per cent, those cells being diffusely distributed in the section. A discrepancy between ER-ICA and the DCC method was thus demonstrated in breast cancer patients treated by endocrine therapy.     

Effects of serum immunosuppressive factors on antitumor cytotoxicity of interleukin 2-induced lymphocytes

The cytotoxic ability of interleukin 2 (IL2)-induced T cells and the effect on their cytotoxicity of serum suppressive factors obtained from cancer patients were examined. Peripheral blood mononuclear cells (PBL) of healthy adults were IL2-cultured for 72 h either together with a gastric carcinoma cell line MKN-28 or with phytohemagglutinin, then IL2-cultured for another 11 days. Cytotoxicity of the MKN-28 precultured lymphocytes against MKN-28 was particularly increased. Presence during preculture or during cytotoxicity assay of sera from gastric cancer patients having the same histological type as MKN-28 suppressed the cytotoxicity. However, the serum suppressive effect on cytotoxicity of the IL2-cultured lymphocytes was far milder than that on PBL cytotoxicity.     

Eradication of Epstein-Barr virus episome and associated inhibition of infected tumor cell growth by adenovirus vector-mediated transduction of dominant-negative EBNA1.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1), a latent viral protein consistently expressed in infected proliferating cells, is essentially required in trans to maintain EBV episomes in cells. We constructed a mutant (mt) EBNA1 and examined whether it exerted dominant-negative effects on maintenance of the viral episome thereby leading to abrogation of EBV-infected tumor cell growth. Using lymphocyte and epithelial cell lines converted with neomycin-resistant recombinant EBV (rEBV) as models, adenovirus vector-mediated transduction of mtEBNA1, but not LacZ, brought about rapid and striking reductions in rEBV-derived wild-type EBNA1 levels and viral genomic loads in converted lines of three major viral latencies. This outcome was further validated at the single-cell level by cellular loss of G418 resistance and viral signals in situ. The mtEBNA1 transduction significantly impaired growth of naturally EBV-harboring Burkitt lymphoma cells in vitro and in vivo, largely in association with the eradication of viral episomes. Expression of mtEBNA1 per se caused no detectable cytotoxicity in EBV-uninfected cells. These results indicate that mtEBNA1 can act as a dominant-negative effector that efficiently impedes the EBV-dependent malignant phenotypes in cells regardless of viral latency or tissue origin. The mutant will afford an additional therapeutic strategy specifically targeting EBV-associated malignancies.     

Factors influencing the release of renin in patients under chronic dialysis treatment.

Plasma renin activities (resting PRA, post-dialysis delta PRA) were studied in 61 patients under chronic dialysis treatment. Removed sodium and removed water were estimated at each dialysis. Delta PRA/removed-sodium and delta PRA/removed-water were calculated as indices in response to the removal of sodium and water during the dialysis. 1)Resting PRA (pre-dialysis PRA) was positively correlated to delta PRA/removed-sodium, delta PRA/removed-water, serum osmolality, and diastolic blood pressure, but negatively to serum sodium concentration, age, and pulse pressure/diastolic blood pressure. Statistically significant factors controlling the resting PRA were delta PRA/removed-sodium, delta PRA//removed-water, and serum sodium concentration. Resting PRA was slightly correlated to diastolic blood pressure and age. 2)Post-dialysis PRA was significantly correlated to the resting PRA, delta PRA/removed-sodium, delta PRA/removed-water, serum sodium concentration, and age, but not to the blood pressure indices.     

Renin Release during Acute Reduction of Arterial Pressure in Normotensive Subjects and Patients with Renovascular Hypertension

In normotensive subjects, acute reduction of mean arterial pressure to from 60 to 75 mm Hg by infusion of sodium nitroprusside caused significant increase in renin activity of renal venous plasma and also in the renal-systemic difference of renin activity. At the same time, the products of the renal-systemic difference of renin activity and renal plasma flow increased significantly, whereas renin substrate activity of plasma was unchanged, indicating that there was an increase in renin release during reduction in pressure. Renin activity of renal venous plasma, expressed in logarithms, showed a significant correlation with the degree of reduction in pressure; an increase in renin activity became significant when mean arterial pressure was reduced to below a level of 70 to 75 mm Hg.     

Genetic polymorphisms and functional characterization of the 5'-flanking region of the human CYP2C9 gene: in vitro and in vivo studies

OBJECTIVE: Genetic polymorphisms were identified in the 5'-flanking region of the human CYP2C9 gene, and their effects on the phenotype were evaluated on the basis of the luciferase reporter gene assay and the in vivo pharmacokinetics of phenytoin. METHODS: Genetic polymorphisms were screened by polymerase chain reaction-single-strand conformational polymorphism analysis, following sequencing with DNA samples obtained from 50 healthy volunteers and 133 adult epileptic patients. HepG2 hepatoma cells were cotransfected with various sequence patterns of 5'-flanking region-luciferase reporter gene constructs. Pharmacokinetic parameters of phenytoin in relation to the corresponding sequence patterns were estimated by the Bayesian method, and the results were compared with in vitro activities. RESULTS: Genetic analysis revealed the existence of 7 single nucleotide polymorphisms (SNPs). Allele frequencies of T-->C transition at position -1912 (T-1912C), C-1886G, C-1566T, G-1538A, C-1189T, G-982A, and A-162G were 0.019, 0.019, 0.077, 0.019, 0.579, 0.019, and 0.003, respectively. Some mutations occurred simultaneously, and a total of 6 sequence patterns (patterns 1-6) were observed. The luciferase reporter gene assay indicated that the presence of mutation(s) resulted in a reduction in luciferase activity of 41.4% (pattern 2) to 86.8% (pattern 5) compared with the activity of the wild-type construct. The calculated intrinsic clearance of phenytoin was also lower (up to a 40% reduction for pattern 2) when a mutation(s) was present. CONCLUSION: In addition to the two major mutations in the coding region (CYP2C9*2 and CYP2C9*3 ), mutations in the 5'-flanking region of the human CYP2C9 gene appear to contribute to the large interindividual variability in drug metabolism activity.     

Rapid and sensitive mycoplasma detection system using image-based deep learning

Journal of Artificial Organs - A major concern in the clinical application of cell therapy is the manufacturing cost of cell products, which mainly depends on quality control. The mycoplasma test,...