Monitoring twenty-six chronic myeloid leukemia patients by BCR-ABL mRNA level in bone marrow:a single hospital experience

Chronic myeloid leukemia (CML) is caused by the BCR-ABL oncogene. The Philadelphia chromosome (Ph) from a reciprocal translocation, t(9;22) (q34;q11) causes a fusion gene, BCR-ABL, that encodes a constitutively active tyrosine kinase. Treatment of CML by imatinib is effective to control the tyrosyl phosphorylation of the protein related to the cell signaling. BCR-ABL mRNA is overexpressed in the minimal residual disease (MRD), known as an early sign of relapse. Between December 2005 and June 2008, we measured BCR-ABL mRNA levels in the bone marrow (BM) from patients by quantitative real-time polymerase chain reaction (RQ-PCR) in Aomori Prefectural Central Hospital. Eighty-six samples from 26 patients were collected. Among the 26 CML patients, 11 patients (42%) were in the pretreatment group. Seven (64%) of the 11 patients achieved complete molecular response (CMR). In the post-treatment group consisting of the remaining 15 patients, 9 (60%) patients achieved CMR. The patients receiving imatinib at a dose over 300 mg per day required 13 (6-77) months [median (range)] to achieve CMR. On the other hand, the patients receiving a dose below 300 mg per day required 29.5 (11-84) months [median (range)]. When BCR-ABL mRNA was detected during the treatment course of patients with CMR, careful observation of BCR-ABL mRNA was useful for tracking the clinical course of patients. In conclusion, the BCR-ABL mRNA level was useful for monitoring the clinical course in 26 patients with CML.     

Characterization and phospholipase D mediation of the angiotensin II priming response in adrenal glomerulosa cells

Bovine adrenal glomerulosa cells are primed by an initial treatment with angiotensin II (AngII) to respond with enhanced secretion to a second exposure to AngII or agents that increase calcium influx. We hypothesized that the mechanism of priming involves a persistent increase in diacylglycerol (DAG) generated via sustained activity of phospholipase D (PLD). In this report, we sought to define the time frame of this priming response as well as determine its mechanism using assays of aldosterone secretion, PLD activation, and radiolabeled diacylglycerol levels. We found that in primary cultures priming was observed for up to 50 min after AngII washout, suggesting that the priming window is protracted in these cultures relative to freshly isolated cells. The phorbol ester, phorbol 12,13-dibutyrate (PDBu), was used to investigate the role of sustained PLD activation in the persistent DAG and priming responses. PDBu was able to both prime glomerulosa cells to respond with enhanced secretion to AngII and elicit a persistent increase in DAG after PDBu washout. This persistent increase in DAG levels with an initial exposure to PDBu or AngII was not the result of maintained PLD activity after agent removal because PLD activation returned to basal levels by 30 min after washout. Finally, inhibition of PLD signaling during the initial AngII treatment inhibited the subsequent response to AngII or another agent that increases calcium influx. Thus, our results suggest that persistent DAG resulting from PLD signaling mediates the priming response to AngII or PDBu.     

Disrupted development of the dominant hemisphere following prenatal irradiation

One hundred children, exposed prenatally to radiation after the Chernobyl nuclear power plant accident, and 50 nonexposed classmates were examined between the ages of 11 and 13 years old using neuropsychiatric tests, WISC, EEG, and visual evoked potentials. Individual prenatal radiation doses were reconstructed for all examined children. The exposed children were found to have more neuropsychiatric disorders, left-brain neurological signs, lower full-scale and verbal IQ, IQ discrepancies with verbal decrement, disorganized EEG patterns, an excess of lateralized-to-left frontotemporal region delta and beta power with depression of theta and alpha power, and interhemispheric inversion visual information processing. Mothers' mental health, stress, and prenatal irradiation contributed to these effects, along with several confounding factors.     

Shear Wave Elastography of Peripheral Muscle Weakness in Patients with Chronic Congestive Heart Failure

Forty-five study participants (28 chronic heart failure [CHF] patients and 17 control participants) were prospectively enrolled in this study to investigate the clinical potential of ultrasound shear wave elastography (SWE) in identifying peripheral muscle weaknesses in chronic heart failure patients. Muscle stiffness in the gastrocnemius muscle during extension (stretch) and the lower arm flexor muscles during flexion was assessed via shear wave elastography, measuring the shear modulus (kPa) for the resting and contractile states in a range of 0–300 kPa. Resting kPa revealed no significant difference between CHF and CP, but exercise kPa for extension and flexion was significantly lower in CHF than CP. The area under the receiver operating characteristic curve of the denominator kPa-Exercise stretch was 0.916, associated with a sensitivity of 89%, a specificity of 71% and a corresponding cutoff value of 81.1 kPa. Shear wave elastography is thus a reproducible and sensitive ultrasound method for evaluating peripheral muscle deficits in patients with CHF.