Increased value of E-rosette test in aseptic meningitis after incubation with CSF

Summary The influence of CSF on the active and total E-rosette test with peripheral blood (PB) lymphocytes of 12 children with aseptic meningitis (AM) was estimated. The control group included 10 children with convulsive fever. An increase in active and total T cells after incubation with CSF was observed in AM. This phenomenon might in part explain the higher proportion of T cells appearing in the CSF during aseptic meningitis. No changes were observed in the control group.     

Herpes simplex encephalitis: A serological follow-up study

A solid-phase radioimmunoassay method was used for the detection of herpes simplex virus (HSV) immunoglobulin M (IgM), IgA, and IgG antibodies within the central nervous system in 11 adult patients with acute HSV encephalitis. Serial cerebrospinal fluid (CSF) and serum specimens were sampled during the observation periods, extending up to 43 months after onset.
The clinical diagnosis of HSV encephalitis was confirmed demonstrating virus or virus antigen in the central nervous system in four patients and with significant HSV antibodies in CSF in all the patients. In acute stage CSF HSV antibodies of a significant level were demonstrated in one of four samples taken on days 3–4 after onset, and in samples taken on days 6–8 in five of nine patients. CSF HSV antibodies of a significant and high level were detected in all samples taken from day 10 after onset.
Intrathecal production of HSV IgM and IgA antibodies lasted from 7 weeks to 43 months during the observation periods. All patients had persistent intrathecal production of HSV IgG antibodies as well as of oligoclonal IgG during the total observation periods up to 43 months.     

中枢神经系统感染患儿脑脊液的TNF与IL-1β的含量变化及其临床意义

目的 :探讨中枢神经系统感染患儿脑脊液与血浆中的 TNF与 IL- 1β的含量变化。方法 :利用 EL ISA法检测了病毒性脑膜炎 ( VM)、化脓性脑膜炎 ( PM)、结核性脑膜炎 ( TM)早期、恢复期脑脊液 ( CSF)与血浆中肿瘤坏死因子 ( TNF)和白细胞介素 - 1β ( IL - 1β)的含量变化。结果 :VM、 PM、 TM早期 CSF中 TNF、 IL - 1β含量显著高于对照组 ( P<0 .0 1) ,而恢复期与对照组无显著性差异 ( P>0 .0 5 ) ,在急性期 PM、 TM的 CSF中 TNF与 IL - 1β显著高于 VM组 ,血浆中 TNF与 IL - 1β的变化无显著性差异。在早期 CSF中 TNF与 IL - 1β的含量呈直线正相关。结论 :1脑脊液的 TNF与 IL- 1β可以作为中枢神经系统感染的早期诊断指标之一。2脑脊液中 TNF与 IL- 1β是早期鉴别细菌性脑膜炎与病毒性脑膜炎的有效方法之一。 3 TNF与 IL- 1β可能协同参与中枢神经系统感染过程     

Stimulation of oxidative metabolism of granulocytes by recombinant granulocyte-macrophage-colony-stimulating-factor and a conditioned medium of a urinary bladder carcinoma cell line

Summary Neutrophils (PMN) are the major host defence cells protecting the body against invasion by microorganisms. Products of oxidative metabolism mediate PMN microbicidal and tumoricidal activity, but the mechanisms by which these pathways become activated are not well understood. The colony stimulating factors (CSF) are known to stimulate proliferation and differentiation of committed bone marrow stem cells. These regulators may probably play an important role in non specific resistance to infections. We studied the oxidative metabolism of neutrophils after stimulation with recombinant GM-CSF (r.GM-CSF) and the concentrated conditioned medium of the UBC-5637 cell line (UBC-CM) showing CSF activity. It could be demonstrated that the r.GM-CSF, as well as the UBC-CM, induce an activation of the neutrophil respiratory burst without any cofactors such as f-MLP, PMA, or zymosan. In addition, we observed an increase of the response to those stimulants in the presence of either r.GM-CSF or UBC-CM. These effects were not endotoxin-induced, since stimulation persisted after addition of Polymyxin B, which is known to inhibit the action of endotoxins.Presented at the 32nd Annual Meeting of the German Society of Hematology and Oncology, October 1986, Tübingen, Federal Republic of Germany     

Cerebrospinal fluid protein findings in cervical syndromes classified by myelography, and in multiple sclerosis

Determinations of cerebrospinal fluid (CSF) albumin, IgG, albumin blood brain barrier (BBB) permeability and local IgG synthesis indexes in CNS were carried out on 85 patients with various neck, shoulder and upper extremity pain syndromes. CSF was obtained by lumbar puncture in 29, and by lateral neck puncture in 56 of the patients. The patients were classified into 3 different groups according to varying severity of degenerative changes, or cavitation verified by myelography. CSF protein patterns in these patients were compared with lumbar CSF findings in 18 patients with multiple sclerosis. CSF protein changes in patients with abnormal myelographic findings were slight. Protein values were clearly more abnormal in lumbar CSF than in cervical CSF, probably due to a retardation of the CSF flow. Only 3 of 62 patients with a narrowing of the cervical spinal canal had pathological values for IgG synthesis or BBB permeability indexes. On the other hand, 14 of 18 patients with multiple sclerosis had abnormal, high values for the IgG index. Thus the present results suggest that investigation of the CSF protein pattern has value in differential diagnosis between patients with multiple sclerosis and degencrative diseases of the cervical spine.     

Influence of peripheral and intracerebroventricular glucose and insulin infusions on peripheral and cerebrospinal fluid glucose and insulin levels

There is much evidence that glucose and insulin are related to the regulation of food intake and the maintenance of peripheral glucose homeostasis through actions of the central nervous system. However, evidence concerning the penetration of peripheral glucose and insulin into the cerebrospinal fluid (CSF) and the relationship between both peripheral and CSF glucose and insulin levels is still missing. In the reported experiments it is shown that insulin is present in the CSF (17 +/- 3.6 microU/ml CSF versus 44 +/- 6.0 microU/ml plasma) but that CSF insulin does not follow rises of peripheral insulin to 136 microU/ml plasma during 4.5 hours. On the other hand CSF glucose (55 +/- 3.1 mg/dl CSF) follows rises of peripheral glucose levels with a delay of about 30 min. Increase of CSF glucose by infusing glucose into the third brain ventricle elicits a prolonged decrease in peripheral glucose levels. Infusion into the third ventricle of insulin only does not change peripheral glucose. However, infusion of a combination of insulin and glucose in the third ventricle leads to a gradual increase in peripheral glucose and elicits a disappearance of the decrease in peripheral glucose after glucose only infusion into the CSF. During third ventricle infusion experiments no change in peripheral insulin could be observed. It will be argued that changes in CSF glucose and insulin contribute to maintenance of peripheral glucose homeostasis.     

The generation of human innate lymphoid cells is influenced by the source of hematopoietic stem cells and by the use of G‐CSF

NK cells play a central role in the haploidentical HSC transplantation (HSCT) to cure high‐risk leukemias. Other innate lymphoid cells (ILCs) have been proposed to exert a protective role in graft‐versus‐host disease and could also contribute to anti‐microbial defence and to lymphoid tissue remodeling. Thus, we investigated the ILC differentiation potential of HSCs isolated from BM, mobilized peripheral blood (PB), and umbilical cord blood (UCB). BM CD34⁺ cells are enriched in lymphoid‐committed precursors, while PB CD34⁺ cells preferentially contain myeloid precursors. In vitro differentiation experiments revealed that the highest and the lowest CD56⁺CD161⁺ ILC recovery was detected in UCB and PB HSC cultures, respectively. Among CD56⁺CD161⁺ ILCs, the ratio between NK cells and ILC3s was similar for all HSC analyzed. ILC recovery in PB CD34⁺ cultures was lower for G‐CSF‐mobilized HSCs (good mobilizers) than for G‐CSF+plerixafor‐mobilized HSC (poor mobilizers). Moreover, G‐CSF inhibited in vitro ILC recovery and the degree of inhibition was proportional to the time of exposure to the cytokine. Thus, although all common sources of HSC for transplant differentiate towards ILCs, substantial differences exist among different sources and G‐CSF may influence ILC recovery. These data offer new clues for a better understanding of the immune reconstitution after HSCT.     

Alpha‐mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function

Alpha‐mannosidosis (AM) (OMIM 248500) is a rare lysosomal storage disease. The understanding of the central nervous system (CNS) pathology is limited. This study is the first describing the CNS pathology and the correlation between the CNS pathology and intellectual disabilities in human AM. Thirty‐four patients, aged 6–35 years, with AM were included. Data from 13 healthy controls were included in the analysis of the magnetic resonance spectroscopy (MRS). Measurements of CNS neurodegeneration biomarkers in cerebrospinal fluid (CSF), CSF‐oligosaccharides, and performance of cerebral magnetic resonance imaging (MRI) and MRS were carried out. On MRI, 5 of 10 patients had occipital white matter (WM) signal abnormalities, and 6 of 10 patients had age‐inappropriate myelination. MRS demonstrated significantly elevated mannose complex in gray matter and WM. We found elevated concentrations of tau‐protein, glial fibrillary acidic protein and neurofilament light protein in 97 patients, 74% and 41% of CSF samples, respectively. A negative correlation between CSF‐biomarkers and cognitive function and CSF‐oligosaccharides and cognitive function was found. The combination of MRS/MRI changes, elevated concentrations of CSF‐biomarkers and CSF‐oligosaccharides suggests gliosis and reduced myelination, as part of the CNS pathology in AM. Our data demonstrate early neuropathological changes, which may be taken into consideration when planning initiation of treatment.     

Granulocyte‐macrophage colony‐stimulating factor responses of oral epithelial cells to Candida albicans

Candida albicans is the principal fungal species responsible for oropharyngeal candidiasis, the most frequent opportunistic infection associated with immune deficiencies. Cytokines, such as granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), are important in the generation of effective immunity to C. albicans. The purposes of this investigation were to determine whether C. albicans triggers secretion of GM‐CSF by oral epithelial cells in vitro and to investigate mechanisms of host cell–fungal interactions that trigger such responses. Oral epithelial cell lines as well as primary oral mucosal epithelial cells were challenged with stationary phase viable C. albicans, added to human cell cultures at varying yeast:oral cell ratios. Yeast were allowed to germinate for up to 48 h and supernatants were analyzed for GM‐CSF by ELISA. Fixed organisms, germination‐deficient mutants and separation of yeast from epithelial cells using cell culture inserts were used to assess the effects of viability, germination and physical contact, respectively, on the GM‐CSF responses of these cells. Two out of three cell lines and three out of six primary cultures responded to C. albicans with an increase in GM‐CSF secretion. GM‐CSF responses were contact‐dependent, strain‐dependent, required yeast viability and were optimal when the yeast germinated into hyphae.