Interleukin-1, nitric oxide and reactive astrocytes

Recent work in many laboratories has revealed that cytokines are important mediators of inflammation, host defense, and tissue injury in a variety of neurological diseases. A role for astrocytes and microglia in these diseases has been considered pivotal, since both cell types readily produce and respond to cytokines in vitro and show morphologic and immunocytochemical evidence for activation in vivo. Although much of the work documenting these events has been generated in rodent systems, our laboratory has focused on human cell culture systems to define the nature of the activating signals for human microglia and astrocytes and their responses to activating cytokines and growth factors and evidence for activation. The results have shown that interleukin-1 (IL-1) is a potent activator of human astrocytes and induces cytokines such as tumor necrosis factor alpha and interleukin-6, and is a potent activator of nitric oxide generation in astrocytes. Astrocytes also promote microglial growth and differentiation through production of colony-stimulating factors, an activity that is enhanced following activation with IL-1. This review will summarize the human glia data generated in this and other laboratories and present hypotheses how glia may participate in certain human central nervous system diseases.     

Genetic therapy for transplant vascular sclerosis

Red blood cells are still transfused inappropriately in spite of recent media attention and public awareness about the risks of blood products. A prospective audit was conducted to determine the avoidable blood transfusion rates in the elective perioperative setting utilising the guidelines issued by the American College of Physicians (ACP). Of 82 consecutive adult patients who were admitted for major elective surgery over a 3-month period, 28 were transfused a total of 94 units of homologous SAG-M blood, of which 50 (53%) were inappropriate as recommended by the ACP guidelines. Violations of the guidelines were perioperative transfusion in bleeding patients who were haemodynamically stable (31%) and transfusion in asymptomatic, stable patients solely to attain a haemoglobin level above 10 g% (22%). There is a need for objective, easily adaptable and widely disseminated consensus guidelines to the indications for red blood cell transfusion.     

The zeta protein kinase C isoform from the testis of the grey mullet Mugil cephalus with a specific reaction protein of M(r) 48,000 on oolemma

The zeta protein kinase C isoform (PKC-zeta) was purified from the testis of the grey mullet Mugil cephalus and has relative masses (M(r)) of 65,000 and 63,000. The subunits of PKC-zeta from spermatozoa degenerated to M(r) 58,000 and 53,000 after continuous freezing and thawing. Proteins of M(r) 48,000 on the oolemma of the grey mullet Mugil cephalus were found to be the reaction proteins of the PKC-zeta from spermatozoa.     

Inhibition of pink color development in cooked, uncured ground turkey through the binding of non-pink generating ligands to muscle pigments

The pink color defect in cooked, uncured turkey is a sporadic problem that can result in economic loss and consumer dissatisfaction. Fourteen ligands were tested in ground turkey samples for their ability to reduce pink color development in control samples and in the presence of 150 ppm sodium nitrite or 1.0% nicotinamide (pink color producing agents). The 14 ligands evaluated were: 3-amino pyridine (AP), 4-benzoylpyridine (BP), diethylenetriamine pentaacetic acid (DA), ethylenedinitrilo-tetraacetic acid disodium salt (EA), 2,3 dihydroxybenzoic acid (DB), 3-ethyl pyridine (EP), trans 1,2-diaminocyclohexane-N,N,N',N' tetraacetic acid monohydrate (HA), calcium reduced nonfat dried milk (NM), 2,3 phthalic acid (PA), 3-picoline (PC), pyrrole (PY), pyridazine (PZ), pyridinedicarboxcylic acid (YA), and pyrazinedicarboxcylic acid (ZA). All ligands were incorporated into ground turkey at 0.20 mg/g (meat weight basis) except for NM (30 mg/g). Color was evaluated using a reflectance spectrophotometer to measure pigment changes (nicotinamide hemochrome, nitrosohemochrome) and with a chroma meter to determine CIE L* a* b* values. Reduction in pink color development was apparent with the addition of the ligand alone and in the presence of sodium nitrite and especially nicotinamide. The four most effective ligands tested were DA, EA, HA, and NM. In general, pink color reduction was highest in the ligand only and the ligand plus nicotinamide samples as was observed by CIE a* and nicotinamide hemochrome value reductions.     

Airway hyperresponsiveness and cough-receptor sensitivity in children with recurrent cough

In children, recurrent cough is a common presenting symptom that may represent asthma. We tested the hypotheses that children with recurrent cough have increased cough-receptor sensitivity (CRS) or airway hyperresponsiveness (AHR). Skin prick testing, the capsaicin CRS test, and hypertonic saline (HS) challenge were performed in 44 children (median age: 8.9 yr) with recurrent dry cough (> or = 2 episodes of cough, each lasting > or = 2 wk, within a period of 12 mo) and 44 controls. Measures of CRS were the concentration of capsaicin required to stimulate > or = 2 coughs (Cth) and > or = 5 coughs (C5). During the coughing period, Cth (mean log: 0.62 [95% CI: 0.43 to 0.81]) and C5 (mean log: 1.15 [95% CI: 0.86 to 1.44]) of the subjects without AHR were significantly lower (p = 0.0026, 0.027, respectively) than Cth (mean log: 1.27 [95% CI: 0.88 to 1.66]) and C5 (mean log: 1.79 [95% CI: 1.21 to 2.37]) of the subjects with AHR and those of the controls (p = 0.0002 and 0.0001). During the cough-free period, there was no difference in CRS among the groups. In subjects who demonstrated AHR, the provocation dose causing a > or = 15% fall in FEV1 (PD15) during the cough period was significantly lower (p = 0.005) than that during the cough-free period. We conclude that AHR or increased CRS is present during the coughing phase in children with recurrent cough.     

Attachment loss with postmenopausal age and smoking

To determine whether postmenopausal bone loss and factors associated with osteoporosis affect tooth retention, we examined vertebral and proximal femoral (postcranial) bone mineral density in relation to tooth loss and attachment loss in a cross-sectional study of 135 postmenopausal women (age range 41-70 yr). Women had at least 10 teeth and no evidence of moderate or severe periodontal disease. Full-mouth attachment loss measurements were made using a pressure-sensitive probe, and bone density was determined by dual-energy X-ray absorptiometry. Attachment loss was correlated with tooth loss (number of remaining teeth, radiologically determined), but not with vertebral or proximal femur bone density. Multivariate analysis showed current smoking (p = 0.01), years since menopause (p = 0.02) and the interaction of age and current smoking (p < 0.01), to be statistically significant predictors of attachment loss in our study population.     

A potential role for interleukin-15 in the regulation of human natural killer cell survival

Resting lymphocyte survival is dependent upon the expression of Bcl-2, yet the factors responsible for maintaining lymphocyte Bcl-2 protein expression in vivo are largely unknown. Natural killer (NK) cells are bone marrow-derived lymphocytes that constitutively express the beta and common gamma(c) subunits of the IL-2 receptor (R) as a heterodimer with intermediate affinity for IL-2. IL-15 also binds to IL-2Rbeta gamma(c) and is much more abundant in normal tissues than IL-2. Mice that lack the IL-2 gene have NK cells, whereas mice and humans that lack IL-2R gamma(c) do not have NK cells. Further, treatment of mice with an antibody directed against IL-2Rbeta results in a loss of the NK cell compartment. These data suggest that a cytokine other than IL-2, which binds to IL-2Rbeta gamma(c), is important for NK cell development and survival in vivo. In the current report, we show that the recently described IL-15R(alpha) subunit cooperates with IL-2Rbeta gamma(c) to transduce an intracellular signal at picomolar concentrations of IL-15. We demonstrate that resting human NK cells express IL-15R(alpha) mRNA and further, that picomolar amounts of IL-15 can sustain NK cell survival for up to 8 d in the absence of serum. NK cell survival was not sustained by other monocyte-derived factors (i.e., TNF-alpha, IL-1beta, IL-10, IL-12) nor by cytokines known to use gamma(c) for signaling (i.e., IL-4, IL-7, IL-9, IL- 13). One mechanism by which IL-15 promotes NK cell survival may involve the maintenance of Bcl-2 protein expression. Considering these functional properties of IL-15 and the fact that it is produced by bone marrow stromal cells and activated monocytes, we propose that IL-15 may function as an NK cell survival factor in vivo.