Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1-antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.     

Detection of infectious disease agents in tissue by immunocytochemistry

1. Immunocytochemical procedures have played an increasingly larger role in the identification of infectious disease agents in tissue sections owing to the increased availability and specificity of antibody reagents, the great sensitivity of the methods, and the relative facility with which the studies are performed. 2. Immunocytochemical methods can be applied to routine formalin-fixed tissue for the detection of infectious agents such as viruses, bacteria, fungi, and protozoa among other microorganisms for diagnostic and research purposes.     

Big fish in small ponds: a social hierarchy analysis of intergroup bias

High- and low-self-esteem group members received feedback about their individual performance as well as that of their own group and an out-group. They then evaluated both groups. Yoked-control observer individuals also provided group evaluations. In the in-group success/out-group failure condition, in-group enhancement tendencies were attenuated by individual failure feedback and augmented by individual success feedback. Low-self-esteem group members who received individual failure feedback showed favoritism toward the unsuccessful out-group over their own successful in-group. In the in-group failure/out-group success condition, in-group enhancement tendencies were attenuated by individual success feedback and augmented by individual failure feedback. Thus individuals' position in a social hierarchy mediates upward and downward social mobility strategies.     

Chimeric constructs between human and rat equilibrative nucleoside transporters (hENT1 and rENT1) reveal hENT1 structural domains interacting with coronary vasoactive drugs

We have recently isolated cDNAs from human placenta and rat jejunum encoding the prototypic human and rat equilibrative nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporters hENT1 and rENT1. The two proteins (456 and 457 residues, Mr 50,000) are 78% identical in amino acid sequence and contain 11 potential transmembrane segments (TMs) with a large putative extracellular loop between TMs 1 and 2 and a large cytoplasmic loop between TMs 6 and 7. When expressed in Xenopus oocytes, recombinant hENT1 and rENT1 transport both purine and pyrimidine nucleosides, including adenosine, and are inhibited by nanomolar concentrations of NBMPR. hENT1 is also potently inhibited by coronary vasodilator drugs (dipyridamole, dilazep, and draflazine), whereas rENT1 is insensitive to inhibition by these compounds (dipyridamole IC50 values 190 nM (hENT1) and >/=10 microM (rENT1) at 10 microM uridine). In the present study, we have generated reciprocal chimeras between hENT1 and rENT1, using splice sites at residues 99 (end of TM 2) and 231 (end of TM 6), to identify structural domains of hENT1 responsible for transport inhibition by vasoactive compounds. Transplanting the amino-terminal half of hENT1 into rENT1 converted rENT1 into a dipyridamole/dilazep-sensitive transporter, whereas the amino-terminal half of rENT1 rendered hENT1 dipyridamole/dilazep-insensitive. Domain swaps within the amino-terminal halves of hENT1 and rENT1 identified residues 100-231 (incorporating TMs 3-6) of hENT1 as the major site of vasodilator interaction. Since these drugs function as competitive inhibitors of nucleoside transport and NBMPR binding, TMs 3-6 are likely to form part of the substrate-binding site.     

Acute appendicitis following laparoscopic inguinal hernioplasty. Coincidence or complication?]

The Authors report two cases of renal leiomyosarcomas with atypical clinical features. Despite a malignant histological picture, nephron-sparing surgery was performed. The two patients are alive and disease-free at six years and fifteen months respectively. Specific radiologic findings, indications and rationale for conservative treatment are discussed.     

Prevalence of morphologic defects in spermatozoa from beef bulls

OBJECTIVE: To determine the overall prevalence of morphologic defects in spermatozoa from beef bulls and to determine whether prevalence varies with the age of the bull. DESIGN: Cross-sectional observational study. ANIMALS: 2,497 beef bulls that were evaluated for breeding soundness in 1994 by 29 practicing veterinarians in a 5-state geographic region. PROCEDURE: Slides of spermatozoa from each bull were made and submitted by practicing veterinarians for morphologic evaluation. One hundred spermatozoa per slide were examined, and each was classified as having 1 of 9 morphologic defects or as normal. RESULTS: 63% of bulls evaluated were 10 to 12 months old, and 20% were 13 to 18 months old. A mean of 70.6% of spermatozoa was classified as normal. Most common defects were proximal droplets (8.4%), distal midpiece reflexes (6.7%), separated heads (5.5%), and distal droplets (3.8%). Other defects were seen < 2% of the time. Bulls 10 to 12 months of age had a higher prevalence of proximal and distal droplet defects than older bulls. CLINICAL IMPLICATIONS: Practitioners conducting breeding soundness evaluations in beef bulls must be aware of common spermatozoal defects. Bulls that are evaluated at a young age will have more defects than older bulls and should be reevaluated, particularly for those defects for which prevalence decreases with age.