Passive Transfer of Lambert-Eaton Myasthenic Syndrome in Mice: Decreased Rates of Resting and Evoked Release of Acetylcholine from Skeletal Muscle

Mice were injected for 1-2 months daily with 10 mg immunoglobulin G (IgG) from four patients with Lambert-Eaton myasthenic syndrome (LEMS); control mice were injected with pooled human IgG from normal donors. Gastrocnemius muscles were homogenised for the assay of acetylcholine (ACh), choline acetyltransferase (ChAT), and cholinesterase (ChE). The ACh, ChAT, and ChE contents of gastrocnemius muscles from "LEMS mice" were about the same as the control values, which were 180 pmol, 40 nmol X h-1 (37 degrees C), and 15 mumol X h-1 (37 degrees C), respectively. Hemidiaphragms were treated with an irreversible ChE inhibitor (Soman) and incubated at 20 degrees C for estimation of ACh release. Resting ACh release from experimental muscles was reduced by about 25% (P2 less than 0.05) and the release evoked by 3 s-1 nervous stimulation by 50% (P2 less than 0.05). On the other hand, 50 mM KCl-induced transmitter release was not abnormal in LEMS mice. The findings indicate that IgG antibody from patients with LEMS may bind to nerve terminal determinants that are involved in quantal and nonquantal ACh release.     

广谱肾综合征出血热病毒单克隆抗体的A35的生物学性状

具有中和及血凝抑制活性的、能和世界各地分离到的肾综合征出血热病毒(HFRSV)发生反应的、广谱的单克隆抗体(McAb),对HFRSV的诊断和分子生物学研究都有重要意义。 本文着重比较了HFRSV McAbA5、A19、A25-1、A25-7和A35的生物学性状,并观察了对感染动物的实验治疗效果。     

Effect of oxygen limitation on the formation of the electron transport system of the phytopathogenic fluorescent bacteriumPseudomonas cichorii

The composition of the membrane-bound electron transport system of the phytopathogenic bacteriumPseudomonas cichorii underwent modification in response to oxygen supply. Growth adaptation to low oxygen concentrations was characterized by repression of cytochromes involved in ubiquinol-cyt.c oxidoreductase and cyt.c oxidase activities. By contrast, cyto.o, i.e., the alternative cyanide-insensitive oxidase ofP. cichorii, was unaffected by low oxygen tension. Noa-type cytochromes could be detected at any stage of growth.     

Bidirectional effect of met-enkephalin on macrophage effector functions

Summary Met-enkephalin (ME) exerts a bimodal effect on functional activities of rat peritoneal macrophages (PM); in a range of low concentration (10^-9-10^-7 M) antibody dependent cellular cytotoxicity (ADCC)was markedly stimulated with a simultaneous decrease of Fc receptor (FcR) mediated phagocytosis while the opposite was observed at 10^-6-10^-5 M concentrations.Studying the possible underlying mechanism(s) the followings were recorded: (1) ME in all applied concentrations induced an early Na⁺ influx which was followed by a Ca²⁺ efflux in the range of low concentrations. In the range of high concentrations Na⁺ influx was accompanied by a Ca²⁺ influx. (2) ME at 10^-8 M concentration induced a rise in cGMP level with a plateau in the 60–120th min of incubation. This effect was prevented by 10^-5 M of naloxone. At 10^-6 M concentration a transient rise of cAMP level was recorded which was not affected by naloxone. (3) Verapamil in 10^-6 M abolished both the Ca²⁺ influx and the rise in cAMP level induced by 10^-6-10^-5 M ME but not the rise in cGMP level induced by lower ME concentrations. (4) cAMP elevation by high ME concentrations was abolished by enkephalinase inhibitory puromycin. (5) PM-enkephalinase as assessed by the cleavage of fluorogenic substrate L-alanine beta naphthylamide (ABNA), was inhibited by 10^-6-10^-5 M of ME. This inhibition was abolished by verapamil, but not affected by naloxone. In the range of low concentrations ME appears to act on specific delta opioid receptors and its action is positively coupled to guanylate cyclase. In relatively higher concentrations ME-action is not mediated by specific delta opioid receptors and it appears to involve Ca²⁺ influx, adenylate cyclase activation as well as the processing of hormone by PM-enkephalinase.     

Down''s Syndrome Individuals Begin Life with Normal Levels of Brain Cholinergic Markers

We measured the activities of the cholinergic marker enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in autopsied brains of seven infants (age range 3 months to 1 year) with Down's syndrome (DS), a disorder in which virtually all individuals will develop by middle age the neuropathological changes of Alzheimer's disease accompanied by a marked brain cholinergic reduction. When compared with age-matched controls cholinergic enzyme activity was normal in all brain regions of the individuals with infant DS with the exception of above-normal activity in the putamen (ChAT) and the occipital cortex (AChE). Our neurochemical observations suggest that DS individuals begin life with a normal complement of brain cholinergic neurons. This opens the possibility of early therapeutic intervention to prevent the development of brain cholinergic changes in patients with DS.     

Regional Reductions of Transketolase in Thiamine-Deficient Rat Brain

Abstract: Thiamine deficiency impairs oxidative metabolism and causes metabolic encephalopathy. An early reduction in transketolase (TK) activity may be an important pathogenic event. To assess the role of TK, we have delineated the regional/cellular distribution of TK protein and mRNA in adult rat brain in pyrithiamine-induced thiamine deficiency. TK activity declined in both vulnerable and spared regions. Immunoblots showed a parallel reduction of TK protein. With a few exceptions, immunocytochemistry indicated an overall decline of TK immunoreactivity and the decrease was not specific to vulnerable areas. In contrast to the pronounced, general decline of TK protein, in situ hybridization revealed a regional decrease of 0–25% of TK mRNA in thiamine deficiency. Northern blots indicated a similar level of TK mRNA in whole brain in thiamine deficiency. These results show that the decline of TK activity results from a proportional decrease of TK protein, and the deficiency may be due to an instability of TK protein or an inhibition of TK mRNA translation. The lack of correlation of the distribution, and the absence of specific alteration, of TK in affected regions suggest that the reduced TK may not be linked directly to selective vulnerability in thiamine deficiency.     

Ethanol Inhibits Basic Fibroblast Growth Factor-Mediated Proliferation of C6 Astrocytoma Cells

Abstract: Early ethanol exposure alters the proliferative activity of glial and neuronal precursors in the developing CNS. The present study tests the hypothesis that ethanol-induced alterations in cell proliferation result from interference with growth factors. An in vitro model of astroglia (C6 astrocytoma cells) was used to study the effects of ethanol on proliferation mediated by basic fibroblast growth factor (bFGF). bFGF stimulated the proliferation of C6 cells. This bFGF-enhanced proliferation was evident by increases in total cell number, DNA synthesis (as measured by [³H]thymidine incorporation), and the number of cells that took up bromodeoxyuridine. A synthetic peptide that specifically blocked the binding of bFGF to its high-affinity receptor completely abolished the proliferation-promoting effect of bFGF. The action of another mitogen for C6 cells, insulin-like growth factor-1, was not affected by this peptide. Therefore, the bFGF-stimulated proliferation was mediated through a specific bFGF receptor. Ethanol inhibited bFGF-mediated proliferation in a concentration-dependent manner. Ethanol concentrations of 100 and 200 mg/dl partially inhibited bFGF-mediated proliferation (by 58 and 74%, respectively), whereas concentrations of ≥400 mg/dl completely abolished the growth-stimulating effect of bFGF. Our data show that ethanol alters proliferative activity of C6 cells by disrupting the action of bFGF. The target of ethanol neurotoxicity is a receptor-mediated activity. bFGF can affect cell proliferation by a non-receptor-mediated intracellular pathway, but ethanol does not have an impact on this pathway.     

A unique genomic sequence in the Wolf-Hirschhorn syndrome [WHS] region of humans is conserved in the great apes

The Wolf-Hirschhorn syndrome (WHS) is caused by a partial deletion in the short arm of chromosome 4 band 16.3 (4p16.3). A unique-sequence human DNA probe (39 kb) localized within this region has been used to search for sequence homology in the apes' equivalent chromosome 3 by FISH-technique. The WHS loci are conserved in higher primates at the expected position. Nevertheless, a control probe, which detects alphoid sequences of the pericentromeric region of humans, is diverged in chimpanzee, gorilla, and orangutan. The conservation of WHS loci and divergence of DNA alphoid sequences have further added to the controversy concerning human descent.     

Rapid Increase of Pneumococcal Resistance to β-Lactam and Other Antibiotics in Isolates from the Respiratory Tract (Nagasaki,Japan: 1975–1994)

The susceptibility of 101 pneumococcal isolates from the respiratory tract during 1991–1994 was examined and compared with the susceptibility of isolates over the period of 1975–1990. A rapid increase of resistance was seen not only to penicillin but also other antimicrobial agents. During 1991–1994, 38% of all the isolates were resistant to penicillin. The rates of resistance during this period were 16–23% for three newer cephalosporins, 18% for imipenem, 69% for tetracycline, 31% for erythromycin, 20% for chloramphenicol and 9% for clindamycin. The use of antibiotics within one month prior to pneumococcal isolation was correlated with penicillin resistance (P < 0.05). Serotyping of the isolates by antiserum revealed differences in predominant types between penicillin-resistant (19F, 23F, 4) and -susceptible isolates (15, 4, 11A). Our data suggests that anti-pneumococcal antibiotics should be carefully chosen on the basis of susceptibility tests.     

Proliferation and Teratogenicity of Aino Virus in Chick Embryos

Aino virus (AIV; JaNAr 28 strain) 10³ TCID₅₀/0.2 ml was inoculated in the yolk sac of 8-day-old chick embryos. Recovery and titration of the virus from various organs including the central nervous system (CNS) and skeletal muscle were performed at 2, 4, 7, 10 and 13 days after inoculation (PI). AIV was systemically disseminated and proliferated even 2 days PI. The titers of the recovered virus from the CNS and from skeletal muscle was the highest at 4 days PI and declined with time, whereas hydranencephaly, arthrogryposis and cerebellar hypoplasia developed at 7 days PI and gradually progressed until 13 days PI.