Immunoglobulin Gene Rearrangement in Plasma Cell Dyscrasias: Detection of Small Clonal Cell Populations in Peripheral Blood and Bone Marrow

The bone marrow (BM) and peripheral blood (PB) samples of 71 patients with plasma cell dyscrasias were analysed by the Southern blot technique for the presence of clonal immunoglobulin (Ig) gene rearrangements. 53% of BM samples examined were archival material such as air dried BM slides or frozen trephine biopsies. The results were related to bone marrow plasmacytosis as determined by cytology and flow cytometry, and other clinical parameters. Clonal Ig gene rearrangements were found in BM samples of 45 (83%) of 54 MM patients and in 3 of 6 patients with monoclonal gammopathy of unknown significance (MGUS). Clonal cell populations in the PB were detected in 11 (30%) of 37 examined MM patients, but in none of the patients with MGUS or solitary plasmacytoma of bone. PB involvement was associated with progressive disease. Circulating monoclonal cells were significantly associated with higher M-protein levels (p 0.05). Thus, circulating clonal precursor cells are encountered more frequently in active MM.     

Influence of Electromagnetic Fields on Function of Automated External Defibrillators

Objectives: In this study, the authors tested whether electromagnetic interference (EMI) is able to impair correct electrocardiogram analysis and produce false‐positive shock advice from automated external defibrillators (AEDs) when the true rhythm is sinus. Methods: Nineteen healthy subjects were used to test five AEDs available on the Austrian market in a prospective, open, and sequence‐randomized study. The primary outcome variable was the absolute number of shocks advised in the presence of EMI. The secondary outcome was the number of impaired analyses caused by incorrectly detected patient movements or electrode failure. Results: Of 760 tests run, 18 (2.37%) cases of false‐positive results occurred, and two of five AEDs recommended shocks in the presence of sinus rhythm. Of 760 tests run, no electrode failures occurred. There were 27 occurrences (3.55%) of motion detected by an AED in the presence of strong electromagnetic fields. Conclusions: AED models differ in their response to EMI; it may be useful to consider specific safety requirements for areas with such fields present. Working personnel and emergency medical services staff should be informed about potential risks and the possible need for patient evacuation before AEDs are attached and shock recommendations are followed.     

Electrodynamics and ultimate SNR in parallel MR imaging.

The purpose of this article is to elucidate inherent limitations to the performance of parallel MRI. The study focuses on the ultimate signal-to-noise ratio (SNR), which refers to the maximum SNR permitted by the electrodynamics of the signal detection process. Using a spherical model object, it is shown that the behavior of the ultimate SNR imposes distinct limits on the acceleration rate in parallel imaging. For low and moderate acceleration, the ultimate SNR performance is nearly optimal, with geometry factors close to 1. However, for high reduction factors beyond a critical value, the ultimate performance deteriorates rapidly, corresponding to exponential growth of the geometry factor. The transition from optimal to deteriorating performance depends on the electrodynamic characteristics of the detected RF fields. In the near-field regime, i.e., for low B0 and small object size, the critical reduction factor is constant and approximately equal to four for 1D acceleration in the sphere. In the far-field wave regime the critical reduction factor is larger and increases both with B0 and object size. Therefore, it is concluded that parallel techniques hold particular promise for human MR imaging at very high field.     

Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity.

Corticotropin-releasing hormone receptor type 1 (CRH-R1)-deficient mice display reduced anxiety-like behavior, a chronic corticosterone deficit, and an impaired neuroendocrine stress response caused by disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. The molecular substrates and pathways of CRH/CRH-R1-dependent signaling mechanisms underlying the behavioral phenotype as well as the consequences of lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling of brains of CRH-R1 mutant and wild-type mice using our custom made MPIP (Max Planck Institute of Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered expression levels when comparing CRH-R1 knockout mice with wild-type littermates. A significant proportion of differentially expressed genes was related to control of HPA and hypothalamic-pituitary-thyroid (HPT) axes reflecting not only the disturbance of the HPA axis in CRH-R1 mutant mice but also the interplay of both neuroendocrine systems. The spatial analysis of regulated genes revealed a prevalence for genes expressed in the cerebral microvasculature. This phenotype was confirmed by the successful cross-validation of regulated genes in CRH overexpressing mice. Analysis of the cerebral vasculature of CRH-R1 mutant and CRH overexpressing mice revealed alterations of functional rather than structural properties. A direct role of the CRH/CRH-R1 system was supported by demonstrating Crhr1 expression in the adult murine cerebral vasculature. In conclusion, these data suggest a novel, previously unknown role of the CRH/CRH-R1 system in modulating neurovascular gene expression and function.     

Estrogenic regulation of heat shock protein 90 kDa in the rat ventromedial hypothalamus and uterus.

The regulation of heat shock protein 90 kDa (hsp90) by estradiol was analyzed in the rat ventromedial hypothalamus (VMH) and uterus by one-dimensional gel electrophoresis/Western blots. Protein from VMH and uterus (35 micrograms/sample) was resolved on 8% acrylamide gels, transferred to polyvinyldifluoride filters, and processed for immunoblotting using an anti-hsp90 antibody. Hsp90-specific bands were visualized on film using enhanced chemiluminescence and quantitated using a laser scanning densitometer. Hsp90 protein levels were significantly elevated in VMH at 12 h (p less than 0.01), and in uterus at 18 h (p less than 0.05) following estradiol injection (10 micrograms, s.c.). Immunocytochemical analysis for hsp90 localization by cell types showed that, in brain, hsp90 immunoreactivity was primarily neuronal. In the uterus, hsp90 immunoreactivity was most evident following treatment with estradiol, and was found primarily in the glandular epithelia; staining was less prominent in myometrium, stroma, and in the luminal epithelium. Thus, increased hsp90 levels may mediate some cellular responses to estrogen in specific cell types in both uterus and brain.     

Altered corticomotor representation in patients with Parkinson's disease.

In 6 patients with Parkinson's disease (PD) and 6 age-matched controls, transcranial magnetic stimulation was applied at 56 regions over the motor cortex and premotor cortex of each hemisphere, with the first dorsal interosseous (FDI) muscle of both hands activated at 15% maximum voluntary contraction during stimulation. For each site, motor evoked potential (MEP) landmarks were recovered, including MEP amplitude, MEP onset latency, and silent period duration. Scaled MEP amplitudes were used to construct individual cortical maps of the FDI muscles. The maps revealed an anterior displacement of the muscle representation in PD patients. This anterior shift over motor cortical areas may reflect increased contributions of corticocortical connections between motor cortex and premotor cortical areas, possibly enhanced by the visual feedback aspect of the task. These alterations may reflect adaptations to the impairments in striatocortical circuits in PD.     

Axial muscle EMG responses evoked by cutaneous flank nerves in the female rat: effects of spinal transection, steroid hormones, and anesthesia.

In the lateral longissimus muscle (LL) of ovariectomized, female rats anesthetized with low surgical doses of urethane (1.0 g/kg), cutaneous reflexes with similar EMG and response patterns could be elicited from CNS-intact rats and from rats 24 h after complete thoracic spinal cord transection. The probability of eliciting a response to contralateral cutaneous nerve stimulation alone is much lower in rats with complete spinal transections compared to CNS-intact rats. For both CNS-intact and spinal-transected rats, responses to ipsilateral cutaneous nerve stimulation had a shorter latency and required significantly less current on average than responses to contralateral stimulation. The respective currents for eliciting threshold responses to ipsi- and contralateral stimulation are less for CNS-intact than spinal-transected rats. For both CNS-intact and spinal-transected rats, responses to bilateral cutaneous nerve stimulation were inconsistent in the same animal from run to run. With the variability of response at this anesthetic level, no consistent effects of progesterone (acute, i.v.) or estrogen (acute, i.v. and pretreatment, s.c.) were observed in spinal-transected rats. Intravenous progesterone reduced early, unilateral responses in CNS-intact rats anesthetized with 1.0 g of urethane/kg. For both CNS-intact and spinal-transected rats, additional anesthesia during EMG recording produced a gradual decline in response magnitude which could be recovered with a modest increase in stimulus intensity. However, spinal-transected rats appear to require less anesthesia to reduce comparable responses. The results suggest that supraspinal input is especially effective for facilitating contralateral cutaneous reflexes in back muscles, whereas it contributes more equally with afferent input and segmental circuitry to the efficacy of ipsilateral cutaneous reflexes.