The erythrocyte as instigator of inflammation. Generation of amidated C3 by erythrocyte adenosine deaminase.

Myocardial ischemia is characterized by the liberation of adenosine and by complement-mediated inflammation. We have reported that amidated C3, formed when ammonia (NH3) disrupts the thiolester bond of C3, serves as an alternative pathway convertase, generates C5b-9, and stimulates phagocytic oxidative metabolism. We investigated whether the deamination of adenosine by adenosine deaminase in hematopoietic cells might liberate sufficient ammonia to form amidated C3 and thereby trigger complement-mediated inflammation at ischemic sites. In the presence of 4 mM adenosine, NH3 production per erythrocyte (RBC) was equal to that per neutrophil (PMN) (3.3 X 10(-15) mol/cell per h). Because RBC outnumber PMN in normal blood by a thousandfold, RBC are the major source of NH3 production in the presence of adenosine. NH3 production derived only from the deamination of adenosine by the enzyme adenosine deaminase and was abolished by 0.4 microM 2'-deoxycoformycin, a specific inhibitor of adenosine deaminase. When purified human C3 was incubated with 5 X 10(8) human RBC in the presence of adenosine, disruption of the C3 thiolester increased more than twofold over that measured in C3 incubated with buffer, or in C3 incubated with RBC (P less than 0.05). The formation of amidated C3 was abolished by the preincubation of RBC with 2'-deoxycoformycin (P less than 0.001). Amidated C3 elicited statistically significant release of superoxide, myeloperoxidase, and lactoferrin from PMN. Thus, the formation of amidated C3 by RBC deamination of adenosine triggers a cascade of complement-mediated inflammatory reactions.

Bax accelerates tumorigenesis in p53-deficient mice.

Bax is a Bcl-2 family member that promotes apoptosis and counters the protective effect of Bcl-2. Bax is a downstream effector of p53-induced apoptosis and is transcriptionally regulated by p53. Moreover, the introduction of Bax deficiency accelerates the onset of tumors in transgenic mice expressing truncated large T antigen. These results implicate Bax as a tumor suppressor. Consequently, we asked whether the levels of Bax expression would influence tumor development by comparing Bax-deficient and Bax transgenic mice in the presence or absence of p53. We found that Bax-deficient mice did not display an increased incidence of spontaneous cancers when followed for > 1.5 years. In addition, Bax-deficiency did not further accelerate oncogenesis in mice also deficient in p53. We generated Lck(pr)-Bax transgenic mice to examine the effects of overexpressed BAX on T-cell development and tumorigenesis. Lck(pr)-Bax mice show increased apoptosis consistent with the pro-apoptotic function of Bax. The introduction of p53-deficiency did not interfere with BAX-induced apoptosis; this is consistent with BAX operating downstream or independent of p53. However, we found that Lck(pr)-Bax/p53-deficient mice have an increased incidence of T-cell lymphomas when compared with p53-deficient mice. The Lck(pr)-Bax transgenic mice have an increased percentage of cells in cycle. These findings extend previous work suggesting that Bcl-2 family proteins regulate proliferation as well as cell death. We conclude that BAX-induced proliferation is synergistic with a defect in apoptosis contributed by p53-deficiency. Thus, the dual roles of BAX can either accelerate or inhibit tumorigenesis depending on the genetic context.

Septicemia in pediatric oncology patients: the significance of viridans streptococcal infections.

One hundred nine consecutive episodes of septicemia were retrospectively evaluated in 61 children with malignancy. In addition, the records of all pediatric oncology patients who received high-dose cytarabine (HDAC) chemotherapy were reviewed. Gram-positive organisms accounted for 82.6% of the septicemic episodes. In the total group, coagulase-negative staphylococci and viridans streptococci accounted for 35.8% and 28.4% of the episodes, respectively. In granulocytopenic patients, viridans streptococci were the most common pathogens (36.8%). In the subset of patients who received HDAC, 62.5% of the septicemic episodes were caused by viridans streptococci. Pulmonary complications developed in nine (29%) of the total cases of viridans streptococcal sepsis, whereas these complications occurred in only eight (10.3%) of the septic episodes caused by other organisms. In patients who had viridans septicemia, prior treatment with HDAC did not increase the incidence of pulmonary complications. In septic children with malignancy, our results demonstrate a high incidence of gram-positive organisms, including viridans streptococci, which were once regarded as culture contaminants.

Priming of tyrosine phosphorylation in GM-CSF-stimulated adherent neutrophils.

Adherence of human neutrophils to plastic, fibronectin, or collagen-coated surfaces modifies their response to several agonists including granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha), and fMet-Leu-Phe, permitting them to trigger superoxide anion (O2-) release, which they are unable to do as cells in suspension. Adherence of neutrophils causes a slight decrease in the basal level of tyrosine phosphorylation compared with that of suspended cells. The addition of GM-CSF, however, brings all proteins to a level of phosphorylation at least equal to that seen in suspended cells. In the case of a 130-kDa (p130) and a 42-kDa (p42) protein, the increase in tyrosyl phosphorylation in response to GM-CSF challenge is clearly larger in adherent than in suspended cells (6- and 4-fold increases for p130 and p42, respectively, in adherent cells vs. 1.7- and 2.1-fold in suspended cells). This is even more patient in the case of collagen-coated plates (9.4-fold increase for p42). Therefore, once neutrophils attach to surfaces, they become primed and respond to GM-CSF with greater potency than when they are in suspension. By Western blot analysis with anti-MAP kinase antibodies, we demonstrate that p42 is one member of the mitogen-activating protein kinase, namely the p42MAPK. The tyrosyl phosphorylation of p42MAPK is elevated in GM-CSF-treated adherent neutrophils in a time-dependent fashion as measured by the formation of a doublet composed of the phospho (or activated) form and the dephospho (or inactive) form of MAP kinase. MAP kinase activation and tyrosine phosphorylation are inhibited by tyrosine kinase inhibitors genistein and tyrphostin-23. Our results indicate that adherence acts to prime neutrophils for enhanced functionality and that tyrosine phosphorylation is involved in this process.

Superoxide production by rat neutrophils in the oleic acid model of lung injury.

The purpose of this study was to investigate the superoxide anion (O2-)-generating capacity of neutrophils isolated from rats at various stages of oleic acid(OA)-induced lung injury. Neutrophils were collected from blood, bronchoalveolar lavage (BAL), and peritoneal cavity (glycogen induced) after OA administration. Control neutrophils were collected from the blood of normal animals as a representative of nonprimed cells that produce low levels of O2-. A second control was the glycogen-elicited peritoneal neutrophil of normal animals which represented primed cells that produce enhanced levels of O2-. The ability of the neutrophils to produce O2- was evaluated by using both myristate acetate and opsonized zymosan as stimulants. Neutrophils isolated from blood and BAL from OA-injured lungs produced low levels of O2- and resembled closely the circulating, nonprimed neutrophil. Myeloperoxidase levels were measured in plasma and BAL and were found to be elevated in BAL of OA-injured animals. The inability of neutrophils to produce high levels of O2- and the elevation of myeloperoxidase suggest that neutrophils present in the lung may have degranulated in response to prior activation and are therefore incapable of further superoxide production.

Enhancement of neutrophil function for treatment of neonatal infections.

Newborn infants are at increased risk of morbidity and mortality from infection despite the continued development of new antibiotics. Because impairment of such host defense mechanisms as PMN function is thought to be largely responsible for this problem, correction of these defects in neonates offers a new and potentially important therapy against infection. Further studies are necessary to determine whether transfusion of either adult PMNs, antibody or fresh frozen plasma; administration of immunomodulating drugs; or some combination of these will provide maximum therapeutic benefit for the newborn infant with infection.

Assessment of adherence with medications in human immunodeficiency virus-infected children.

The purpose of this study was to determine the reliability of screening for medication adherence in HIV-infected children. The results suggest that caregivers who are unable to describe the medication regimen or who are nonadherent with appointments are unlikely to adhere to the medication regimen. Adherence with at least 90% of medication doses was associated with a virologic response.

The correlation between surface measurement of head and neck posture and the anatomic position of the upper cervical vertebrae.

STUDY DESIGN: Repeated measurements were made of surface postural angles registering the relative positions of the head and neck in photographs and of angles of the upper cervical vertebrae recorded in lateral cephalometric radiographs in the same subjects. For all registrations, subjects assumed the natural head rest position. OBJECTIVES: To examine the correlation between external measurement of head and neck posture and the anatomic positions of the upper four cervical vertebrae. SUMMARY OF BACKGROUND DATA: Interpretation of surface cervical posture measurement is confounded by lack of knowledge about the extent of the underlying compensatory adjustments among the upper cervical vertebrae that may accompany variation in head and neck posture. The correlation between surface measurement and postural characteristics of the upper cervical spine has not been reported to date. METHODS: The association between a set of angles describing the anatomic position of the four upper cervical vertebrae on lateral cephalometric radiographs and a surface measurement of head and neck posture, the craniovertebral angle, was studied in 34 young adult women aged between 17.2 and 30.5 years, mean age, 24.5 years. Anatomic positions of the upper four cervical vertebrae were expressed by angles relative to the true vertical or horizontal. Surface angles registering head and neck position for each subject were obtained from photographs recorded on two occasions. RESULTS: No strong correlation could be established between the angles taken from the lateral cephalometric radiographs measuring the extent of upper cervical lordosis, orientation of the atlas, vertebral inclination, or odontoid process tilt and surface angles recording head and neck position. This finding was attributed principally to the much greater positional variability demonstrated within the upper cervical spine when compared with the surface measurements of head and neck position. CONCLUSION: Anatomic alignment of the upper cervical vertebrae cannot be inferred from variation in surface measurement of head and neck posture. This is the case even in those people identified with more extreme head and neck postural tendencies.

The fine connective tissue architecture of the human ligamentum nuchae.

STUDY DESIGN: An anatomic study of the posterior midline structures of the cervical spine was performed using a new sheet-plastination (E12) technique in conjunction with gross anatomic dissection. OBJECTIVES: To clarify the structural status of the human ligamentum nuchae. SUMMARY OF BACKGROUND DATA: Little is known about the arrangement of connective tissue attachments of the neighboring neck muscles to the ligamentum nuchae. In addition, it is not clear whether the cervical supraspinous ligaments form part of the ligamentum nuchae. METHODS: This study used a combined approach of a detailed gross anatomic study on eight cadavers and a macroscopic and microscopic study of the connective tissue organization of the posterior midline structures on serial horizontal thin (2.5 mm) plastinated slices of the cervical spine (occiput-T1) from an adult female cadaver. RESULTS: The dorsal and ventral portions of the ligamentum nuchae are a single entity formed by the aponeurotic fibers of the trapezius, splenius capitis, rhomboideus minor, and serratus posterior superior muscles. CONCLUSIONS: The regional differences in the connective tissue organization of the ligamentum nuchae and its well-defined attachments to the C6 and C7 vertebrae suggest that it is designed to function in the lower cervical spine.

Vaccination update. Diphtheria, tetanus, pertussis, mumps, rubella, measles.

Despite the availability of many effective vaccines, some vaccine-preventable diseases still cause significant morbidity and mortality. Increased prevention should be attainable through proper education about the efficacy and safety of vaccines, improved immunization rates, and adherence to recommended vaccination guidelines from the Advisory Committee on Immunization Practices. Childhood immunization should include a complete diphtheria, tetanus, and pertussis series and a measles, mumps, and rubella series. Booster doses for tetanus should be given every 10 years throughout life.

Vaccination update. Hib, hepatitis, polio, varicella, influenza, pneumococcal and meningococcal disease.

Immunization of infants and children is the most effective strategy for decreasing the incidence of some infectious diseases. Most invasive disease due to Haemophilus influenzae type b occurs before age 5 years, and routine vaccination of infants for hepatitis B is currently recommended because selective immunization of high-risk persons has not been feasible. Decades of use of poliovirus vaccine has effectively eliminated cases of wild-virus infection, although some vaccine-related cases still occur. The newly approved varicella vaccine appears to be a cost-effective way to decrease infection rates in children. Improved immunization rates for influenza and pneumococcal and meningococcal diseases could help decrease excess mortality in elderly persons and those with chronic illness.

Relationships between adolescent drug use and parental drug behaviors.

The present study examined some previously reported relationships between drug use by adolescents and perceived attitudes and behaviors of their parents. An anonymous questionnaire was administered to the student body of an inner-city secondary school for difficult students. Relationships between parental use of drugs and adolescent use of the same drugs were moderate and roughly equivalent across drugs. However, parental use of marijuana was strongly related to the adolescent's use of other, harder drugs such as opiates, cocaine, amphetamines, and barbiturates. This finding is explained within the framework of Kandel's postulated stages of drug initiation. It points to a need for further study of parental influences, which may be increasingly problematic as more individuals who have grown up in our marijuana-accepting society become parents of adolescents.

Autologous blood transfusion. Current trends, nursing implications.

Developing a quality perioperative autologous blood recovery program is a team effort. Members of transfusion committees, hospital blood bank personnel, OR staff members, and the members of the surgery committee are all possible sources of information. Your local blood center also may have literature or services that could be of assistance. Knowledge of current autologous transfusion alternatives will help nurses communicate with patients regarding transfusion therapy and will make nurses more valuable participants in the crucial decisions necessary to deliver optimal patient care in the perioperative period.