The role of serum in interleukin 1 production by human monocytes activated by endotoxins and their polysaccharide moieties

Lipopolysaccharides (LPS) as well as polysaccharide (PS) moieties of Bordetella pertussis and Neisseria meningitidis endotoxins induced in vitro interleukin 1 (IL 1) secretion by human monocytes as evaluated by the co-mitogenic assay on C3H/HeJ thymocytes. Because of the role of serum in the specific binding of endotoxins to monocytes mediated by the polysaccharide region [12], experiments were undertaken to study the effect of serum on IL 1 induction. Although the presence of serum is not necessary for the secretion of IL 1 by monocytes stimulated by LPS or PS, the addition of very small amounts of human serum (0.1-1.6%) to the cultures of human adherent cells potentiated the IL 1 secretion, without modifying the background values. Natural anti-B. pertussis antibodies present in the serum were not responsible for the observed phenomenon. Heating at 56 degrees C for 30 min did not alter the enhancing effect. The data presented suggest that the serum component(s) and the IL 1 inducers (LPS or PS) act in synergism by two different pathways since the two signals can be delivered sequentially.     

β Chain deficiency in three patients with dysfunctional C8 molecules

Structural and functional studies were performed on a dysfunctional C8 molecule present in the serum of two siblings and an unrelated individual. The C8 in these three sera exhibited a pattern of partial immunologic identity with C8 in normal serum but was devoid of functional activity. The C8 was immunoprecipitated from the three sera and from a control serum with an antihuman C8 antiserum and analyzed by SDS-PAGE using highly purified human C8 as a reference. A selective absence of a band of 62,000 mol. wt was observed in the immunoprecipitates from the sera containing dysfunctional C8. Experiments performed with the purified α-γ and γ subunits showed that the hemolytic activity of the C8 deficient sera could be reconstituted by the addition of the β chain but not the α-γ dimer. Binding of the dysfunctional C8 to C$\text{567}$ was excluded by the following observations: (1) EAC 1–7 treated with the C8 deficient sera and then washed could not be lysed after the addition of the β subunit and C9; and (2) the abnormal molecules did not interfere with the consumption of normal C8 by the soluble complex SC5b-7.     

Evidence of genetic variation for α-N-acetyl-D-glucosaminidase in black and white populations: A new polymorphism

Serum and/or plasma samples from 360 Whites and 126 Blacks were assayed for activity of the lysosomal hydrolase α-N-acetyl-D-glucosaminidase (NAG). The samples from the Blacks had an increased mean (0.50 nm/ml/min) and standard deviation (0.30 nm/ml/min) compared to those from the Whites (0.29 nm/ml/min and 0.10 nm/ml/min, respectively). After log_e transformation and admixture analysis, it was possible to demonstrate the presence of 3 distributions of NAG activity in Blacks and at least 2 in Whites. Segregation analysis of the NAG activity of 29 White half-sib twin families indicated that a genetic model for the inheritance of NAG activity provided a better fit (P < 0.01) with the data than the “environmental” model. Thus, the study suggests the presence of a genetic polymorphism for NAG activity in Black and White populations. The presence of alleles for high and low NAG activity in the normal population could lead to incorrect interpretation of serum carrier tests for Sanfilippo syndrome, type B.     

Different spinal effects of opioid agonists on spinal and spino-bulbo-spinal reflexes in rats

Summary The effects of morphine-HCl (MOR), methionine-enkephalin (ME) and dynorphin_1–13 (DYN) on spinal and spino-bulbo-spinal (SBS) reflexes were studied. Although spinal intrathecal administration of MOR (15g) did not produce any apparent effect on these reflexes, systemically administered MOR (3mg/kg i.v.) reduced the electrical toe stimulation-induced SBS reflex. Furthermore, MOR (3mg/kg i.v.) increased the polysynaptic reflex induced by electrical stimulation of low-threshold dorsal root afferents in intact (non-spinal) rats, but not in spinal rats. Intrathecally administred DYN (0.5 and 5 g) reduced both the electrical toe stimulation-induced spinal and SBS reflexes, while ME (15g) only reduced the SBS reflex. These results indicate the physiological multiplicity of spinal opioid receptors. MOR may affect supraspinal nuclei but not the spinal pathway which possesses MOR-sensitive opioid receptors, whereas ME and DYN affect spinal opioid peptide receptors and modulate the reflex activities in which they participate.     

Effects of chronic antidepressant treatment on α1- and α2-adrenoceptors in the rat anococcygeus muscle

Summary The effects of a single administration (48 hours) and of chronic (14 days) treatment with tricyclic (desipramine, nortryptiline) and nontricyclic (mianserin, nomifensine) antidepressant drugs on responses of the isolated anococcygeus muscle to the ₂-adrenoceptor agonist xylazine (inhibition of contraction to field stimulation at 1 Hz) and to the ₁-adrenoceptor agonist phenylephrine (contraction of the muscle) have been studied.Of the drugs used only desipramine and nortryptiline administered chronically reduced the responsiveness of the anococcygeus muscle to phenylephrine suggesting a desensitization of postsynaptic ₁-adrenoceptors. Long-term but not acute administration of antidepressants resulted in significant decrease in sensitivity of presynaptic ₂-adrenoceptors to xylazine. These results show that the adaptative changes of -adrenoceptors in the rat anococcygeus muscle following long-term administration may depend on the efficiency to inhibit the neuronal uptake and the ability to antagonize ₁-adrenoceptors.     

Lateral Mobility of the Cell Adhesion Molecule L1 Within the Surface Membrane of Morphologically Undifferentiated and Differentiated Neuroblastoma Cells

Lateral mobility and localization in the surface membrane of the adhesion molecule L1 was studied in morphologically undifferentiated and differentiated neuroblastoma cells to gain insight into its possible association with the different molecular forms of N-CAM. In undifferentiated cells, the fraction of mobile L1 molecules is high and similar to that of N-CAM 140. Upon long-term morphological differentiation, the fraction of mobile L1 molecules is reduced by a factor of three and is similar to that of N-CAM 180, the predominant molecular form of N-CAM in differentiated neuroblastoma cells. Comparable to N-CAM 180, L1 is also preferentially accumulated at contact sites between these cells as seen by indirect immunofluorescence. These observations raise the question of whether at least part of the L1 molecules may be directly or indirectly (e.g. via N-CAM 180) linked to the cytoskeleton, thus stabilizing cell contacts between differentiated cells.     

Some Actions of 9-Amino-1,2,3,4-Tetrahydroacridine (THA) on Cholinergic Transmission and Membrane Currents in Rat Sympathetic Ganglia

THA (Tacrine) is an anticholinesterase drug reported to alleviate cognitive deficit in Alzheimer's disease. We have used rat isolated superior cervical sympathetic ganglia as a model mammalian cholinergic neural system to study effects of THA on cholinergic synaptic transmission and postsynaptic membrane currents. At 0.1 - 3 microM, THA augmented the postsynaptic depolarizations and inward clamp currents produced by acetylcholine but not by the cholinesterase-resistant analogue, DMPP. Higher concentrations depressed these responses to both acetylcholine and DMPP, and reduced the acetylcholine-induced increase in membrane current noise. At 1 microM, THA did not affect the amplitude or time-course of fast (nicotinic) excitatory postsynaptic currents (epscs) evoked by single orthodromic volleys, but higher concentrations induced a biphasic epsc decay. In contrast, low concentrations of THA (1 - 3 microM) greatly augmented and prolonged the muscarinic slow epsc evoked by repetitive orthodromic volleys: this effect was blocked by 1 microM atropine. Concentrations above 0.1 mM produced a membrane depolarization and inhibited a variety of membrane ionic currents, including voltage-gated Ca current and subsequent Ca-activated K currents, and voltage-gated M- and A-type K currents. It is concluded that the principal effect of THA is to inhibit cholinesterase, and that the main consequence of this is to augment and prolong the muscarinic slow epsc. In contrast, the nicotinic fast epsc is not increased but instead may be reduced through a nicotinic channel-blocking action. Although THA could also block several other ion channels the concentrations required were too high to contribute significantly to its principal pharmacological actions on ganglionic transmission.     

Cross-desensitization Reveals Pharmacological Specificity of Excitatory Amino Acid Receptors in Isolated Hippocampal Neurons

Ionic currents elicited by excitatory amino acids were studied, using the concentration clamp method, in enzymatically isolated rat hippocampal neurons. Cross-desensitization between the responses to various agonists was applied to separate the activity of two types of receptors, N-methyl-d-aspartate (NMDA) and non-NMDA. NMDA receptors were selectively activated by NMDA, l- and d-aspartate, d-glutamate and quinolinate. Kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate appeared to be selective, and quisqualate relatively less selective non-NMDA agonists, acting on the same receptor type. l-Glutamate, l- and d-homocysteate activated both receptor types. It is supposed that two receptor sites, activation site and desensitization site, control the action of agonists at the non-NMDA receptor. When examined in the cross-desensitization experiments, NMDA and non-NMDA receptors appear to be represented by the two homogeneous and independent receptor populations operating different ionic channels.     

A critical review of chemical lymph node clearance and staging of colon and rectal cancer at Ferguson Hospital, 1977 to 1982

A unique opportunity to evaluate the method of chemical lymph node clearance for colorectal cancer exists at Ferguson Hospital. Lymph node clearance has been used at the institution since 1977, and this retrospective analysis was undertaken to ascertain its validity there. Furthermore, the node positive group was evaluated to ascertain if the current staging system (Turnbull, 1967) is prognostically accurate for the Dukes' C group. Specifically evaluated for possible prognostic variance was the survival of those patients whose tumors demonstrated partial bowel wall penetration and only one to four positive nodes, a C1 subset, previously reported to have favorable prognosis. Eight hundred sixty-four cases of colon and rectal cancer treated surgically from 1977 to 1982 were analyzed. There was a mean of 27 lymph nodes retrieved per specimen and a mean of 4.5 positive nodes per Dukes' C specimen. There were 43 C1 and 201 C2 cases with five-year survival rates of 73 and 38 percent, respectively. The results of chemical clearance at Ferguson Hospital were found to be comparable with that of other centers using chemical clearance and superior to hand dissection. The C1 subset clearly is noted to have prognostic advantage and should occupy a separate designation in any staging system.Read at the meeting of the American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.Presented at Gramec Research Day, Grand Rapids, Michigan, May 10, 1988.     

Detection of traumatic myocardial injury by means of simultaneous T1-201/Tc-99m pyrophosphate tomography--report of three cases

Trauma to the chest can result in cardiac damage, which maybe missed by clinical examination because of associated injuries.Routinely performed non-invasive tests may also be non-diagnostic.Tc-99m pyrophos-phate (PPi) tomography, in this study combinedwith T1-201, is a promising addition to non-invasive evaluation.In three patients with cardiac injury, this technique successfullydetected and localized myocardial necrosis.