Antigen-independent adhesion of CD45RA (naive) and CD45RO (memory) CD4 T cells to B cells.

We found that naive (CD45RA+) CD4 T cells have a lower capacity of adhesion to Epstein-Barr virus (EBV) immortalized B cells than memory (CD45RO+) CD4 T cells, as judged by conjugate formation. This would appear to be due to differences in the expression of adhesion molecules [lymphocyte function-associated antigen (LFA)-1, CD2]. However, kinetic studies showed that the degree of adhesion of naive T cells to B cells was stable over 60 min while that of memory T cells, like that of unseparated CD4 T cells, was characterized by a rapid formation and rapid dissociation of conjugates. This could be explained by a difference in the sensitivity of naive and memory CD4 T cells to down-regulation of antigen-independent adhesion by CD4-MHC class II interaction. Indeed, memory T cells also adhered stably to MHC class II(-) B cells. The adhesion of memory T cells, but not naive T cells, to MHC class II(+) B cells was sensitive to inhibition by OKT4a an anti-CD4 antibody, human immunodeficiency (HIV) gp160 (env) protein and a 12-mer peptide encompassing the 35-46 sequence of the HLA, DR beta 1 domain and previously shown to inhibit activation of HLA class II-restricted CD4 T cell responses. Since MHC class II expression did not influence the degree of conjugate formation by naive or memory CD4 T cells with B cells, CD4-MHC class II interaction does not appear to be involved in binding itself, but may down-regulate the adhesion of memory but not naive CD4 T cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropathological Effects of Triphenyl Phosphite on the Central Nervous System of the Hen (Gallus domesticus)

The neurotoxic effects of single subcutaneous injections of1000 mg triphenyl phosphite (TPP)/kg body weight were investigatedin White Leghorn hens. At 7 days postexposure, birds began toshow signs of mild to moderate ataxia that progressed to severeataxia and paralysis at 21 days. Inhibition of whole brain neuropathytarget esterase was 85% at 48 hr and 73% by 21 days postexposure.After postexposure periods of 7, 14, and 21 days, hens werekilled and their brains and spinal cords were examined for degeneratingaxons and terminals using the Fink-Heimer silver impregnationmethod. A small amount of degeneration was noted at 7 days.By 21 days, dense degeneration was noted in the spinal graymatter and funiculi. Degeneration was also present in the granularcell layer of cerebellar folia I-VI and in nuclei and fibertracts of the medulla. Moderate to dense degeneration was alsoseen in several forebrain and midbrain areas including the paleostriatum,ansa lenticularis, the dorsointermediate thalamic nucleus, lateralspiriform, pedunculopontine tegmental, and lateral mesencephalicnuclei and in the deeper layers of the optic tectum. These resultsindicate that, in addition to affecting the spinal cord andbrainstem, exposure to TPP also damages higher order centersresponsible for processing and integrating sensorimotor, visual,and auditory information.     

The evolution of ischemic cerebral infarction in infancy: a sonographic evaluation

Cranial sonography provides a noninvasive, portable method for imaging the infant brain. This study describes the time-dependent, sonographic findings of infantile cerebral infarction, as well as computed tomographic (CT) scan and neuropathologic confirmation. Three hundred ninety-five infants under 18 months of age were sonogrammed over a period of 18 months. Three infants were diagnosed by cranial sonography and confirmed by CT scan and/or autopsy to have acute ischemic cerebral infarcts. The cases were followed with serial cranial sonograms for up to 18 months of age. The acute sonographic findings included a hyperechoic zone around the infarcted tissue. The subacute infarct had a checkerboard pattern, while the chronic infarcts were anechoic.     

Effects of histamine on inositol phosphates and intracellular Ca2+ in human glomerular epithelial cells

The effect of histamine on the phosphoinositide turnover andintracellular free calcium activity [Ca²⁺]_i was examined inhuman glomerular epithelial cells in culture. Addition of histamineto glomerular epithelial cells resulted in formation of inositolphosphates in a time- and dose-dependent manner. A transientmaximum of inositol trisphosphate (InsP₃) was observed within10 s. Stimulation of protein kinase C by short-term pretreatment(15 mm) of glom erular epithelial cells with phorbol 12-mynstate13-acetate caused a dose-dependent inhibition of the histamine-inducedinositol phosphate accumulation. The baseline of [Ca²⁺]_i inthe cells was 115 ±2.7 nmol/l (n=103). Histamine (ED₅₀:approx. 2x10^–7mol/l) caused a rapid and transient increasein [Ca²⁺]_i, as detected by fura-2 microfluorimetry studies.In a calcium-free extracellular solution the rapid increaseof [Ca²⁺]_i was still present. The H₁ receptor antagonist mepyramine(IC₅₀: approx. 8 x 10^–9 mol/l) inhibited the histamine(10^–6 mol/l) response on [Ca²⁺]_i Cimetidine, a potentH₂ receptor antagonist, showed no effect. This data indicates that H₁ receptor activation causes hydrolysisof phosphatidylinositol 4, 5-bisphosphate by phospholipase Cactivation, and consecutive mobil ization of intracellular calcium.Since histamine is a mediator of inflammation, antigen responseand cellular injury, these findings could be of importance forthe understanding of glomerular epithelial cell pathology.     

Effects of aprotinin on endothelium-dependent relaxation of large coronary arteries

Objective: Aprotinin is widely used in heart surgery for reduction of intraoperative blood loss. But recent reports presenting results from rat aorta experiments claimed that aprotinin selectively impairs endothelium-dependent relaxation (EDR) as well as basal NO availability in concentrations similar to doses routinely used in cardiovascular surgery. An impairment of coronary EDR by aprotinin would be a great danger for any cardiothoracic intervention. We therefore tested the influence of aprotinin in the coronary arteries of a non-rodent species. Methods: Fresh coronary arteries of pigs were obtained from the local slaughterhouse and transported to our laboratory in cold oxygenated Krebs–Henseleit solution. Five-millimeter long rings were consecutively tested with or without aprotinin in concentrations of 500 KIU/ml (n = 7) or 1000 KIU/ml (n = 6) in oxygenated normothermic Krebs–Henseleit solution. PGF₂ (10 μmol/l) was used for inducing contraction and substance P (10 nmol/l) for inducing EDR, which was calculated in percentage of the precontraction. Indomethacin (10 μmol/l) was added in all measurements to eliminate the influence of prostaglandins. In additional similar experiments (n = 5), the influence of 1000 KIU/ml aprotinin on the EDR caused by the endothelium-derived hyperpolarizing factor (EDHF) was tested using l-NNA (300 μmol/l) to block all NO formation. Results: The EDR of pig coronaries (82 ± 5% or 80 ± 5% of the precontraction in the control tests before and after aprotinin exposure) was not significantly changed by 500 KIU/ml aprotinin (78 ± 7%). A small, but significant reduction of less than 1/10 of the EDR was induced by 1000 KIU/ml aprotinin (74 ± 5%). After accounting for l-NNA for NO blockage, no aprotinin-related difference remained (59 ± 6% vs 60 ± 6% in controls). Conclusion: For clinically relevant concentrations of aprotinin up to 500 KIU/ml, no significant reduction of the EDR can be found in epicardial coronary arteries of the pig. For higher doses of 1000 KIU/ml, a reduction in NO production seems to be the cause of the small but significant reduction of the EDR by aprotinin. Therefore, danger for impairment of coronary EDR by aprotinin at clinical dosage levels, as suggested by studies on rat aortas, seems to be absent in coronary arteries of a large mammalian model.     

In vivo study of degradation of poly-(D,L-) lactide and poly-(L-lactide-co-glycolide) osteosynthesis material]

AIMS. Comparison of the degradation of poly(D,L)lactide (Resorb X) or poly(lactide-co-glycolide) (LactoSorb) in vivo. MATERIAL AND METHODS. LactoSorb and Resorb X osteosynthesis plates were fixed at the lateral aspect of the femora of 26 Chinchilla rabbits using the respective osteosynthesis screws. After intraperitoneal injection of fluorochromes the screw plate bone blocks were resected after 1, 6, 12, 14, 16, 21, 26 months and radiologic, histologic as well as fluorescence microscopic examinations were carried out. RESULTS. Newly formed bone was detectable above and beneath the polymers 1 month after the implantation. The implants were totally covered by newly formed bone after 6 months. While the LactoSorb screws were found to be as birefringent as after 1 month, in the Resorb X screws a continuous resorption by phagocytizing marrow cells starting from the periphery was detectable. Resorb X was totally resorbed in histologic slides 12 months after implantation, while total resorption of LactoSorb lasted 14 months; both polymers were replaced by marrow cells. Bone remodeling was not finished 26 months after implantation in both polymers. CONCLUSION. Resorption of Resorb X was finished earlier than the resorption of LactoSorb. Both materials were found by fluorescence microscope to be completely resorbed after 12 or 14 months, but bone remodeling of the screw holes was not yet finished 26 months after implantation.