Developmental alterations in N-methyl-D-aspartate stimulated [3H]norepinephrine release in rat brain cortex and hippocampus

Developmental alterations in N-methyl-D-aspartate (NMDA)-stimulated[3H]norepinephrine release from rat brain cortical and hippocampal slices were studied. NMDA (10-1000 microM) resulted in a concentration-dependent increase in [3H]norepinephrine efflux; maximal responses (% released) in the cortex were: (1.53 +/- 0.12, 3.68 +/- 0.20, 2.94 +/- 0.20, 4.60 +/- 0.28 and 5.28 +/- 0.33) and the hippocampal responses were: (1.90 +/- 0.18, 3.84 +/- 0.23, 3.60 +/- 0.28, 5.16 +/- 0.38 and 5.81 +/- 0.45) at varying postnatal ages (1, 7, 14, 21 and 90 days) respectively. Cortical tissue from 7-day-old pups exhibited a transient increase in maximal efflux and a decrease in EC50. These results indicated that developmental alterations in the NMDA receptor appear to be translated into differences in NMDA stimulated [3H]norepinephrine release.     

Noninvasive assessment of hepatobiliary and renal elimination of cysteinyl leukotrienes by positron emission tomography

N-Acetyl-leukotriene E4 has been identified as an endogenous, biologically less active cysteinyl leukotriene metabolite in rodents and humans. To evaluate the ratio of hepatobiliary to renal elimination of leukotrienes noninvasively by positron emission tomography (PET), we synthesized N-[11C]acetyl-leukotriene E4 by chemical N-acetylation of leukotriene E4. After the intravenous injection of N-[11C]acetyl-leukotriene E4 in normal rats and monkey, uptake by the liver and subsequent excretion into bile were largely responsible for its rapid elimination from blood. In the Cynomolgus monkey, renal excretion of the leukotriene into urine was of additional quantitative importance. Kinetic modeling indicated a mean transit time through the liver of 17 minutes and 34 minutes in rat and monkey, respectively; the corresponding hepatic excretion half-times amounted to 8.5 minutes and 16 minutes. In a mutant rat strain deficient in the hepatobiliary excretion of cysteinyl leukotrienes across the canalicular membrane, the apparent mean liver transit time was 54 minutes, and the hepatic excretion half-time was 29 minutes, indicating prolonged organ storage and metabolism. After transport from the liver back into the circulating blood of omega-oxidized and beta-oxidized metabolites of N-[11C]acetyl-leukotriene E4, renal excretion compensated for the impairment of hepatobiliary elimination in the transport mutant. Metabolite analyses in urine after intravenous injection of N-[3H]acetyl-leukotriene E4 indicated the extensive inactivation of N-acetyl-leukotriene E4 by beta-oxidation from the omega-end in the mutants. A similar shift from hepatobiliary to renal cysteinyl leukotriene elimination was monitored in rats with cholestasis due to bile duct obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)     

C3a is a chemotaxin for human eosinophils but not for neutrophils. I. C3a stimulation of neutrophils is secondary to eosinophil activation

Inflammatory action of the potent chemotaxin C5a has been well characterized on a variety of human cell types, including neutrophils, monocytes, basophils, and eosinophils. The cellular effects of C3a are less well defined. Contradictory reports have been published for C3a activation of neutrophils. Recent reports that C3a activates both basophils and eosinophils prompted us to reinvestigate the effects of C3a stimulation on eosinophils. We hypothesized that C3a activation of eosinophils, cells that are present in most neutrophil preparations, might lead to neutrophil activation. Using neutrophils of 98% purity, we observed no evidence of cellular activation after stimulation with either C3a, recombinant human C3a (rhC3a), or the synthetic C3a analogue C3a 57-77, Y57. Eosinophils purified to > 98% purity displayed concentration-dependent polarization, chemotaxis, and enzyme release by stimulation with C3a, rhC3a, and the synthetic C3a analogue. An inactive form of C3a, C3adesArg, failed to stimulate either eosinophils or neutrophils. Using neutrophil preparations containing 5-9% eosinophils, up to 20% of neutrophils became polarized after exposure to C3a. Likewise, we demonstrated that supernatant from C3a-stimulated eosinophils promotes neutrophil chemotaxis. Eosinophil polarization experiments were repeated in the presence of antibody to the C5a receptor (C5aR) to show that C3a and C5a interact with different receptors. C3a activates eosinophils in the presence of anti-C5aR antibody at concentrations that fully block C5a activation. We conclude that eosinophils are directly activated by either C3a or C5a, whereas C3a failed to activate neutrophils. C3a acts on eosinophils via a receptor that is distinct from C5aR. Since neutrophils are indirectly stimulated by C3a, eosinophils contaminating neutrophil preparations may explain earlier reports that C3a activates human neutrophils.     

Results of irradiation treatment in patients with non-resectable oesophageal cancer

Forty-eight patients with non-resectable cancer of the oesophagus and oesophagogastric junction (Group A: Stage I/II, 32; Group B: Stage III/IV, 16) underwent intraluminal Iridium-192 high dose-rate afterloading therapy (5-7 Gy/session, total dose: 5-21 Gy, mean: 12.4 Gy) and external beam irradiation (Karnofsky > or = 80% 50-60 Gy/2 Gy per day; Karnofsky 60-79%: 30 Gy/3 Gy per day). Durable satisfactory palliation (intake of at least semi-solid food) was demonstrated in 96% of patients. The mean survival for group A was 19.1 months and that for group B, 6.9 months, with a 12-month survival rate of 66% (group A) and 0% (group B) (P < 0.001). Local tumour response and complication rate were significantly dose-related with a predicted response rate of 70.5%, and a complication rate of 50% at ERD 129.3 Gy.     

The differential regulation and secretion of proteinases from fetal and neonatal fibroblasts by growth factors

Until recently, research on the pathogenesis of glomerulonephritis has been mainly focused on the characterization of humoral immune responses in the initiation of glomerular injury. However, there is a growing recognition that both cellular and humoral immune responses, in varying proportions, are involved in the pathogenesis of immunologically-mediated glomerulonephritis. T lymphocytes are essential cellular elements of cell-mediated immunity. Both in experimental models of immune-mediated renal disease and in histopathological analyses of human nephropathies, the involvement of T cells has been demonstrated in the immunoregulation of nephritogenic immune responses and in the immune injury in the kidney. T cell activation resulting in either delayed-type hypersensitivity, cytolytic reactions, abnormal expression of major histocompatibility complex (MHC) molecules, or B cell activation can result in glomerulonephritis. These different types of responses are exerted by distinct T cell subsets defined by cell surface markers and cytokine profiles. CD4+ T cells in vivo are functionally heterogeneous with respect to cytokine production and the CD45 isoforms that are found on their surface. Like CD4+ T cells, CD8+ T cells may also be heterogeneous at the level of cytokine production. The roles of CD4+ and CD8+ cells and their cytokine profiles in glomerulonephritis have not been extensively investigated yet, but such studies might improve the understanding of the pathogenesis and possibly lead to new therapeutic approaches of human glomerulonephritis. In this review the role of distinct T lymphocyte subsets in experimental and human glomerulonephritis will be discussed.     

Vascularized bone flap for access to the maxillary sinus

PURPOSE: This article describes a vascularized bony window for access to the maxillary sinus and reports the clinical results. PATIENTS AND METHODS: A bony U-shaped window in the anterior sinus wall was pedicled on the surrounding soft tissue and periosteum. After the described sinus was cleared of disease, the window was repositioned in its original site either using resorbable sutures or not. The method was used in 47 maxillary sinus operations in 45 patients. Twenty-four patients were followed-up for more than 48 months. RESULTS: The vascularized bony window technique showed uneventful healing in all patients and none of the 24 patients reported any problems. CONCLUSIONS: The vascularized bony window technique provides a large antrostomy, which gives good access and visibility and results in satisfactory postoperative healing.     

A mixed-signal RAM decision-feedback equalizer for disk drives

A mixed-signal RAM decision-feedback equalizer (DFE) that operates at 90 Mb/s is described. In the analog domain, the DFE subtracts intersymbol interference caused by the past four outputs. The equalized signal is fed into a nonuniform flash analog-to-digital converter (ADC) to produce the decision output and error signal used to adapt the RAM contents in the digital domain. With a 5 V supply voltage, the power dissipation is 260 mW during steady-state operation. The active area is 4.5 mm² in a 1 μm CMOS process