Urinary Excretion of Nitric Oxide, Cyclic Gmp, and Catecholamines During Rest and Activity Period in Transgenic Hypertensive Rats

Dysregulation of the system of nitric oxide (NO)-cyclic 3',5'-guanosine monophosphate (cGMP) might be involved in the development of hypertension in transgenic hypertensive TGR(mREN2)27 (TGR) rats. The present study was performed to determine possible differences in the day-night pattern and the urinary excretion rates of NO and cGMP in TGR rats in comparison to normotensive Sprague-Dawley (SPRD) controls. In addition, the urinary excretion of creatinine and catecholamines was measured in both rat strains. The day-night excretion patterns of NO, cGMP, catecholamines, and creatinine were preserved in TGR rats. Urinary excretion of NO was significantly decreased in TGR rats, whereas cGMP, the second messenger of NO, was elevated in the transgenic animals. Catecholamines and creatinine excretion rates did not differ between the strains. In conclusion, data suggest that a reduced NO synthesis could contribute to the increased blood pressure in the severely hypertensive rats. However, these data make it unlikely that the disturbances in the nitric oxide-cGMP system and the sympathetic nervous system are mainly responsible for the inverse circadian blood pressure rhythm in TGR rats.     

Prolongation of inspiration during lower airway occlusion in children

Inspiration is strongly inhibited by volume-related vagal afferents in human neonates and animals, but this reflex is not as active in human adults during normal breathing. To determine whether volume-related inspiratory inhibition occurs beyond the neonatal period, we performed 10 +/- 1 end-expiratory occlusions in nine asleep children, ages 2-29 mo, with cuffed tracheostomy or endotracheal tubes in place. Airflow, tidal volume, occlusion pressure, and surface diaphragm electromyogram (DIA EMG) were simultaneously recorded. Occlusion consistently increased mechanical (P less than 0.002) and neural inspiratory times (P less than 0.001). During occluded respiratory efforts, peak amplitude of DIA EMG increased by 22 +/- 10% (P less than 0.002). In contrast, initial rate of rise of DIA EMG did not change. We conclude that in children with isolated lower airways, end-expiratory occlusions prolonged inspiratory duration as measured by both mechanical and neural parameters. The lack of an associated increase in rate of rise of DIA EMG strongly suggests that inspiration is prolonged by release of volume-related inhibition of inspiration rather than by facilitation. These data provide evidence for the presence of the Hering-Breuer reflex beyond the neonatal period.     

Chronobiologic Evaluation of Angiotensin-Converting Enzyme Activity in Serum and Lung Tissue from Normotensive and Spontaneously Hypertensive Rats

Angiotensin-converting enzyme (ACE) activity in serum and lung tissue from both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) was determined at six different circadian times. In WKY rats serum ACE varied significantly within 24 h, mainly due to reduced enzyme activity at 12:00 h. In SHR the 24-h profile of serum ACE did not exhibit time-dependent differences. Mean serum ACE activity over 24 h was significantly higher in WKY than in SHR. In lung tissue ACE activity did not depend on the circadian time in either strain. Mean enzyme activity in lung tissue was not different between WKY and SHR. We conclude that circadian changes in the activity of serum and tissue ACE are unlikely to play an important role in the regulation of the circadian blood pressure profile in both normotensive and spontaneously hypertensive rats.     

Separation of immunoreactive lymphocytes from human pluripotent stem cells (CFU-GEMM) by means of counterflow centrifugation

Counterflow centrifugation with continuous monitoring of the output for cell number and cell scatter was used to separate low density (d less than 1.070 g/ml) human bone marrow cells in two fractions: one containing the majority of small size lymphocytes and the other the majority of the larger sized committed progenitor cells. The recovery of the pluripotent stem cells (CFU-GEMM) in the large cell fraction was complete. The mitogenic reactivity of this putative stem cell fraction had decreased to 6% and 11%, of the original value as measured with phytohemagglutinin stimulation and one way mixed lymphocytic culture respectively. Counterflow centrifugation offers a physical separation technique, by which the majority of the immunoreactive cells can be separated from the pluripotent hematopoietic stem cells.     

The BCR gene encodes a novel serine/threonine kinase activity within a single exon.

Sequences encoded by the first exon of BCR that bind to the ABL SH2 domain are essential for the activation of the ABL tyrosine kinase and transforming potential of the chimeric BCR-ABL oncogene. The normal cellular BCR gene encodes a 160,000 dalton phosphoprotein associated with a serine/threonine kinase activity, but it shows only weak dispersed homologies to protein kinases. p160c-BCR was purified to apparent homogeneity as an oligomer of greater than 600,000 daltons that contains autophosphorylation activity and transphosphorylation activity for several protein substrates. A region containing paired cysteine residues within the 426 amino acids encoded by the first exon of BCR is essential for its novel phosphotransferase activity, which overlaps with the strong SH2-binding regions. The recent demonstration of a GTPase-activating function within the C-terminal portion of BCR suggests that the protein kinase and SH2-binding domains may work in concert with other regions of the molecule in intracellular signalling processes.