Cardio-pulmonary function during acute unilateral occlusion of the pulmonary artery in broilers fed diets containing normal or high levels of arginine-HCl

Cardio-pulmonary function was measured in male broilers reared on diets formulated to contain 1.5% arginine (NORMAL group) or 2.5% arginine (ARGININE group). A snare placed around the right pulmonary artery permitted acute shunting of the entire cardiac output (CO) through the left pulmonary artery, resulting in sustained increases in blood flow (BF) through the left lung in both groups. The unilateral increase in BF was accompanied by sustained increases in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in the NORMAL group. However, following initial transient increases in PAP and PVR in the ARGININE group, subsequent pulmonary vasodilation gradually reduced PVR, and thus PAP, in spite of the ongoing elevation of BF through the left lung. The capacity of the pulmonary vasculature in the ARGININE group to accommodate an increased BF at a normal PAP accounts for the previously reported lower incidence of pulmonary hypertension syndrome (PHS, ascites) in cold-stressed broilers fed supplemental dietary arginine. Hypoxemia and respiratory acidosis ensued rapidly in both groups after tightening the pulmonary artery snare, in spite of a compensatory increase in the respiratory rate. The gradual return of PVR and PAP to presnare levels in the ARGININE group did not eliminate the concurrent ventilation-perfusion mismatch caused by the increased rate of BF through the left lung. Tightening the pulmonary artery snare caused mean systemic arterial pressure (MAP) to drop from control levels of approximately 98 mm Hg to sustained hypotensive levels of approximately 65 mm Hg in both groups. This systemic hypotension was caused by decreases in CO and total peripheral resistance (TPR). The reduction in CO were caused by reduction in stroke volume (SV) rather than heart rate (HR), suggesting that acutely tightening the pulmonary artery snare increased PVR sufficiently to impede left ventricular filling. Accordingly, the maximum increment in PAP attainable by the right ventricle during acute increases in PVR apparently was inadequate to propel the entire CO through the pulmonary vasculature, setting the stage for the congestive right-sided pooling of blood routinely associated with PHS in broilers.     

Molecular basis and species specificity of high affinity binding of vasoactive intestinal polypeptide by the rat secretin receptor

The affinity and specificity of the binding interaction between ligands and their receptors are key for appropriate hormonal regulation of target tissues. However, it is now apparent that vasoactive intestinal polypeptide (VIP) binds to the rat secretin receptor with similar affinity to that for its natural ligand, secretin (Holtmann et al., 1995). In this report, we establish that this is not a characteristic of the human secretin receptor, and use rat-human secretin receptor chimeras, site mutants and truncated receptor constructs to establish the molecular basis for this unusual binding interaction. Of note, isolated N-terminal domains of the rat secretin and the VIP receptors are capable of high affinity binding of VIP. In the recently recognized secretin family of receptors, this domain has six conserved cysteine residues and disulfide bonds that are likely important to achieve the complex conformation critical for this binding. A single acidic residue (Asp98) present in the rat secretin receptor appears to be critical, because a site-mutant changing this to the polar, but uncharged residue present in that position in the human receptor (Asn) eliminates the high affinity binding of VIP. Of interest, a previously identified critical basic residue in VIP (Lys15) provides a candidate for charge-pairing with this residue, potentially aligning the peptide ligand in a nonproductive orientation within this receptor.     

A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

Sympathetic blockade of isolated rat hindlimbs by intra-arterial guanethidine: the effect on blood flow and arterial-venous shunting

In order to improve the understanding of the role of sympathetic nerve degeneration in reimplantation failure, the hindlimbs of eight rats (Group I) underwent near-complete amputation. The soft tissues of the hindlimb were transected at the proximal thigh with the femoral artery, vein and femur left intact. The femoral vessels were clamped and guanethidine was infused into a branch of the femoral artery of the right leg of each animal, while saline was injected into the left leg. The clamps were removed after 15 minutes. A baseline preoperative injection of radiolabeled microspheres was made, and subsequent injections at 6, 12, 18, and 24 hours postoperation. Twelve rats (Group II) were then used to assess the amount of arterial-venous shunting preoperatively (n = 6) and at 18 hours postoperation (n = 6), by venous sampling. Blood flow to both limbs increased postoperation, but there was significantly more flow in the guanethidine treated limb at 18 and 24 hours postoperation. The amount of shunting was approximately 50% in both limbs at 18 hours, as compared to 10% preoperation. These results highlight the potential benefit of guanethidine and other sympathetic blocking agents in reimplantation to increase blood flow, decrease tissue ischemia and increase anastomotic patency rates. They also suggest that sympathetic nerve degeneration did not affect the volume of arterial-venous shunting in this model, but the difference in blood flow was likely due to arteriolar vasospasm. Further study is needed to elucidate the clinical significance of sympathetic nerve degeneration in reimplantation failure.     

The simplified two-pipette technique is more efficient than the conventional three-pipette method for blastomere biopsy in human embryos

Kell and Kx are two quantitatively minor proteins from the human erythrocyte membrane which carry blood groups antigens and are thought to be a metalloprotease and a membrane transporter, respectively. In the red cell membrane, these proteins form a complex stabilized by disulfide bond(s). Phosphorylation status of these proteins was studied, in the presence or absence of effectors of several kinases, either on intact cells incubated with [32P]-orthophosphate or on ghosts incubated with [gamma-32P]ATP. Purification of Kell-Kx complex, by immunochromatography on an immobilized human monoclonal antibody of Kell blood group specificity allowed to establish that (i) neither protein is phosphorylated on tyrosine; (ii) the Kell protein is a putative substrate for Casein Kinase II (CKII) and Casein Kinase I (CKI) but not for protein kinase C (PKC), whereas Kx protein is phosphorylated by CKII and PKC but not by CKI; (iii) Protein Kinase A neither phosphorylates the Kell nor the Kx proteins.     

A magnetic sense amplifier

A new mode of operation of a balanced magnetic circuit is described. With this new mode of operation, which utilizes pulsed current excitation, the detection sensitivity of the magnetic modulator circuit is combined with the high-speed amplification of parametric buildup. This combination permits detection of low-level current pulses applied during a specified time interval of the excitation sequence and provides subsequent amplification of the detected signal. Matched square-loop toroids are used. Signal currents which are a small fraction of the coercive MMF have been successfully detected. The limit of detection sensitivity depends upon the matching of the two cores. The parametric buildup has been made to occur for pump cycle times of 30 μs to 120 μs, depending upon the magnetic material used. The signal information is retained when the pulse excitation sequence is interrupted during buildup because the signal information is stored as a flux unbalance in the two cores during the time interval between excitation pulses. The use of this circuit mode as a sense amplifier for the detection and amplification of sense winding currents in magnetic memories is suggested.     

Archival Appraisal and the Digital Record: Applying Past Tradition for Future Practice

The digital revolution has changed the daily work of archivists. As a result, archivists have refined their analog practices and initiated new ones to accommodate the unique information creation and access needs of users. While limitless storage and technological obsolescence may be surmountable challenges, appraisal continues to be a necessary component of this preservation enterprise. Macro-appraisal—a top-down functional assessment of an organization’s high-level decision making that defines the enduring value of specific bodies of documentary evidence of these creative or administrative processes—is used to facilitate the management of diverse bodies of born-digital records in archives and special collections.