scholarly journals THE PASSAGE OF NEUTRALIZING SUBSTANCE FROM THE BLOOD INTO THE CEREBROSPINAL FLUID IN ACTIVELY IMMUNIZED MONKEYS

1918 ◽  
Vol 28 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss
Keyword(s):  
Cerebrospinal Fluid ◽  
Horse Serum ◽  
Pathological Process ◽  
Immune Serum ◽  
Normal Serum ◽  
Aseptic Inflammation ◽  
Therapeutic Advantage ◽  
Inflammatory Conditions ◽  
Active Complement ◽  
Intraspinal Injection

For the neutralization of the virus of poliomyelitis by antibodies, active complement is not required. In carrying out immunity tests it is imperative to choose a virus of established grade of virulence and to make adequate control observations. The neutralizing substances pass from the blood of actively immune monkeys into the cerebrospinal fluid when the permeability of the meningeal-choroidal complex is increased by an aseptic inflammation such as that induced by an intraspinal injection of horse serum. The immunity bodies in effective neutralizing quantities can be detected in the cerebrospinal fluid as early as 12 hours and as late as 48 hours after the intraspinal injection of horse serum. Doubtless the passage continues as long as the inflammation persists. This ability of the neutralizing substances to pass from the blood into the cerebrospinal fluid under conditions of inflammation doubtless plays an important part in arresting the multiplication of the virus on which the cessation and restoration of the poliomyelitic processes depend. The widespread involvement in the inflammatory conditions of the meninges, choroid plexus, and substance of the nervous organs, accompanied by severe lesions of the blood vessels in the last structures especially, opens the way widely for the passage of antibodies into the cerebrospinal fluid, whence all parts of the nervous tissues are reached, and also, probably, for direct transudation into the affected parts of the spinal cord and brain. The neutralization of the virus on which the continuance of the active pathological process depends is thus readily accomplished. Under these circumstances the use of an alien specific immune serum to anticipate the action of the individual's own immunity products appears logical, while the employment of normal serum has no basis in experiment and would seem not to offer any therapeutic advantage whatever.

scholarly journals THE PASSAGE OF NEUTRALIZING SUBSTANCES FROM THE BLOOD INTO THE CEREBROSPINAL FLUID IN POLIOMYELITIS

1917 ◽  
Vol 25 (4) ◽  
pp. 499-505 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Serum ◽  
Inflammatory Reaction ◽  
Horse Serum ◽  
Immune Serum ◽  
Normal Serum ◽  
Aseptic Inflammation ◽  
Set Up ◽  
Acute Poliomyelitis ◽  
Intraspinal Injection

The cerebrospinal fluid taken very early and quite late in the course of acute poliomyelitis exhibits no neutralizing action on filtered poliomyelitic virus. The blood serum on the 6th day of the disease already contains the neutralizing principles. The injection of sterile horse serum into the cerebrospinal meninges in monkeys increases their permeability, so that they permit the immunity neutralizing principles passively injected into the blood to pass into the cerebrospinal fluid. The passage in passively immunized monkeys takes place during a relatively brief space of time and apparently only while the inflammatory reaction produced by the horse serum is at its height. It is established for monkeys and rendered probable for man that the intraspinal injection of immune serum in poliomyelitis is curative. In monkeys normal serum exerts no such action, and at present nothing can be stated definitely regarding the therapeutic effect of normal serum in man except that probably any benefits which may arise from its employment would be attributable not to the action of the serum as such, but to the escape of circulating immunity principles in the blood made possible by the aseptic inflammation set up by it in the meninges. As the immunity principles appear in the blood only after several days, and the reported favorable effects of the immune serum treatment relate to the first days of illness, the employment of normal serum is thus not indicated, while that of an immune serum is.

scholarly journals THE PASSAGE OF MENINGOCOCCIC AGGLUTININS FROM THE BLOOD TO THE SPINAL FLUID OF THE MONKEY

1919 ◽  
Vol 29 (6) ◽  
pp. 597-603 ◽  
Author(s):  
Harold L. Amoss ◽  
Frederick Eberson
Keyword(s):  
Intravenous Injection ◽  
Salt Solution ◽  
Spinal Canal ◽  
Maximum Concentration ◽  
Horse Serum ◽  
Immune Serum ◽  
Spinal Fluid ◽  
Agglutination Reaction ◽  
Normal Horse Serum ◽  
Intraspinal Injection

Agglutinins for the meningococcus were not found in the spinal fluid of normal monkeys which had received antimeningococcic serum intravenously. The intraspinal injection of isotonic salt solution, normal horse serum, or a culture of living meningococci allows agglutinins for the meningococcus to pass from the blood to the spinal fluid of the passively immunized monkey; and the rate of the passage is affected by the severity of the inflammation induced in the meninges. The rates of elimination from the blood and spinal canal of meningococcic antibodies, as shown by the agglutination reaction, were compared in monkeys treated with immune serum (a) intraspinally, (b) intravenously, and (c) intraspinally and intravenously in combination. (a) When immune serum is given intraspinally the agglutinins are very much diminished after 8 hours and practically disappear at 12 hours. They appear in the blood at the 4th hour after injection and quickly diminish. (b) After intravenous injection of immune serum, when the meninges are inflamed, agglutinins appear in the spinal fluid in small amounts in about 12 hours and increase to the 25th hour. More than one-half of the agglutinins disappear from the blood within 8 hours and remain in low concentration at 25 hours. (c) After combined intraspinal and intravenous injection the agglutinins remain in higher concentration in the spinal fluid and for a longer time than by method (a) or (b). The curve descends after 12 hours, and agglutinins are present at 25 hours. They remain in maximum concentration in the blood for 25 hours.

scholarly journals STUDIES ON VIRULENCE

1932 ◽  
Vol 56 (1) ◽  
pp. 13-25 ◽  
Author(s):  
Lloyd D. Felton
Keyword(s):  
Skeletal Muscle ◽  
Horse Serum ◽  
Immune Serum ◽  
Normal Serum ◽  
Long Period ◽  
Tissue Extracts ◽  
Normal Horse Serum ◽  
Antibody Solution ◽  
Transfer Device ◽  
Made In

From the study of different tissue extracts as media for the growth of pneumococci used in an automatic transfer device, certain inferences are warranted: 1. Media made from calf lung or heart, or from horse skeletal muscle maintain virulence over a long period of time. Conversely, media made from calf spleen lead to a decrease in virulence. 2. Lung medium causes an increase in virulence of seven strains of pneumococci. 3. Virulence is maintained in normal horse serum; but, it rapidly decreases in immune serum, or in pneumococcus antibody solution, a finding which confirms the work of Stryker. Immune serum freed from protective antibody gives results similar to normal serum. 4. Rabbit medium made from the entire animal apparently is less suitable for the maintenance of virulence of pneumococci than medium made in the same way from guinea pig.

scholarly journals LOCALIZATION OF THE VIRUS AND PATHOGENESIS OF EPIDEMIC POLIOMYELITIS

1914 ◽  
Vol 20 (3) ◽  
pp. 249-268 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss
Keyword(s):  
Spinal Cord ◽  
Choroid Plexus ◽  
Horse Serum ◽  
Lymphatic Invasion ◽  
Immune Serum ◽  
The Body ◽  
Ependymal Cells ◽  
Intracerebral Injection ◽  
Aseptic Inflammation ◽  
Set Up

The virus of poliomyelitis is capable of penetrating the retina without producing apparent injury, to reach the central nervous organs. The virus injected into the blood is deposited promptly in the spleen and bone marrow, but not in the kidneys, spinal cord, or brain. Notwithstanding the affinity which the nervous tissues possess for the virus, it is not removed from the blood by the spinal cord and brain until the choroid plexus and blood vessels have suffered injury. The intervertebral ganglia remove the virus from the blood earlier than do the spinal cord and brain. An aseptic inflammation produced by an intraspinous injection of horse serum facilitates and insures the passage of the virus to the central nervous organs, and the production of paralysis. The unaided virus, even when present in large amounts, passes inconstantly from the blood to the substance of the spinal cord and brain. When the virus within the blood fails to gain access to the central nervous organs, and to set up paralysis, it is destroyed by the body, in course of which destruction it undergoes, as a result of the action of the spleen and, perhaps, other organs, diminution of virulence. The histological lesions that follow the intravenous injections of the virus in some but not in all cases differ from those which result from intraneural modes of infection. In escaping from the blood into the spinal cord and brain, the virus causes a lymphatic invasion of the choroid plexus and widespread perivascular infiltration, and from the latter cellular invasions enter the nervous tissues. A similar lymphoid infiltration of the choroid plexus may arise also from an intracerebral injection of the virus. The histological lesions present in the central nervous organs in human cases of poliomyelitis correspond to those that arise from the intraneural method of infection in the monkey. The virus in transit from the blood through the cerebrospinal fluid to the substance of the spinal cord and brain is capable of being neutralized by intraspinous injection of immune serum, whereby the production of paralysis is averted. Carmin in a sterile and finely divided state introduced into the meninges and ventricles sets up an aseptic inflammation, but is quickly taken up by cells, including ependymal cells. When an aseptic inflammation has been previously established by means of horse serum, or when the nervous tissues are already injured by the poliomyelitic virus, the pigment appears to enter the ependymal cells more freely. The experiments described support the view that infection in epidemic poliomyelitis in man is local and neural, and by way of the lymphatics, and not general and by way of the blood. Hence they uphold the belief that the infection atrium is the upper respiratory mucous membrane.

scholarly journals THE RELATION OF THE MENINGES AND CHOROID PLEXUS TO POLIOMYELITIC INFECTION

1917 ◽  
Vol 25 (4) ◽  
pp. 525-537 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Lumbar Puncture ◽  
Horse Serum ◽  
Immune Serum ◽  
The Body ◽  
Protective Function ◽  
Morphological Alterations ◽  
Normal Monkey ◽  
Subcutaneous Tissues

Among the mechanisms which defend the body from infection with the virus of poliomyelitis is the meningeal-choroid plexus complex, which normally is capable of excluding the circulating virus from the central nervous organs. The complex plays a part also in preventing infection from virus present upon the nasal mucosa. Aseptic fluids which irritate, inflame, or even slightly alter the integrity of the meninges and choroid plexus diminish or remove their protective function. Normal monkey or horse serum, isotonic salt solution, and Ringer's and Locke's solutions, when injected into the meninges, promote infection with the virus of poliomyelitis introduced into the blood, the nose, or the subcutaneous tissues. Simple lumbar puncture and the withdrawal and return of the cerebrospinal fluid in normal monkeys, hemorrhage having been absolutely avoided, do not promote infection with virus injected into the blood; while the replacement of the cerebrospinal fluid of one monkey with that of another does in some instances lead to infection. Simple lumbar puncture attended with even very slight hemorrhage opens the way for the passage of the virus from the blood into the central nervous tissues, and thus promotes infection. Hence, changes in the structure or function of the meningealchoroid plexus complex, too slight to be detected by chemical and cellular changes in the cerebrospinal fluid or by morphological alterations, suffice to diminish in an essential manner its protective powers. Of all the irritant fluids tested, immune serum alone injected into the meninges is not succeeded by infection from the virus introduced into the blood. The protective property of the immune serum is capable of overcoming the promoting action of normal monkey and horse serum and the other irritants mentioned. The importance first of the meningeal-choroid plexus complex in preventing infection with the virus of poliomyelitis, and next of immune serum in offsetting the disadvantages and dangers arising from defects in the mechanism is apparent, as is the bearing of the experiments reported on the serum therapy of epidemic poliomyelitis.

Quantitative Nephelometric Microdetermination of Alpha-Globulins in Serum and Cerebrospinal Fluid

1956 ◽  
Vol 2 (3) ◽  
pp. 195-213 ◽  
Author(s):  
Abraham Saifer ◽  
Michael C Zymaris
Keyword(s):  
Cerebrospinal Fluid ◽  
Quantitative Determination ◽  
Salt Concentration ◽  
Protein Fraction ◽  
Specific Interaction ◽  
Normal Serum ◽  
Electrophoretic Method ◽  
Serum Fractions ◽  
Standard Serum

Abstract 1. A micronephelometric method is presented for the quantitative determination of total α-globulins in both serum and cerebrospinal fluid. The method is based on the relatively specific interaction of this protein fraction with the cationic detergent, Octab, at pH 6.65 in collidine-NaCl (.08M) buffer. 2. The various Cohn's protein fractions (Method 6) (25) were investigated with the nephelometric procedure. In comparison with normal serum, Fractions IV-6, IV-1, and IV-4, respectively showed the greatest detergent reactivity per milligram of α-globulin. 3. The variations of such factors as the concentrations of reagents, protein/detergent ratio, and salt concentration were reinvestigated. 4. Analysis of 14 normal and 33 pathologic sera gave excellent checks with the total α-globulin values obtained with the Tiselius electrophoretic method. 5. Application of the procedure to the analysis of the α-globulin content of cerebrospinal fluid required the addition of standard serum to 0.5-ml. aliquots of spinal fluid for stoichiometric results.

scholarly journals EXPERIMENTAL INFECTION WITH INFLUENZA A VIRUS IN MICE

1941 ◽  
Vol 73 (1) ◽  
pp. 43-55 ◽  
Author(s):  
R. M. Taylor
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Lethal Dose ◽  
Virus Titer ◽  
Immune Serum ◽  
Normal Serum ◽  
Sublethal Dose ◽  
Virus Content ◽  
Proportional Increase ◽  
Intranasal Instillation

Following intranasal inoculation of influenza A virus (strain PR8) there is a rapid increase of the virus in the lungs which with large doses reaches a maximum within 24 hours. With smaller doses, although the proportional increase is greater, the maximum concentration is not reached until 48 hours following inoculation. If a lethal dose is administered, the ultimate concentration of the virus in the lungs is the same, irrespective of the size of the dose. If a sublethal dose is given, the titer of the virus in the lungs does not achieve the titer reached in mice receiving a lethal dose. Within 48 hours following inoculation of a sublethal dose the lungs of a mouse may contain at least 76,000 M.L.D., yet the mouse survives. The intranasal instillation of sterile fluid (distilled water, varying concentrations of NaCl, broth, or 10 per cent normal serum) into a mouse sublethally infected produces a sharp rise in the virus content of the lung usually followed by death within 3 to 8 days. If, however, the instillate consists of 10 per cent immune serum, there is no rise in the virus titer, and no apparent harm results from the instillation. The implications of these phenomena are discussed and an hypothesis presented to explain their occurrence.

scholarly journals Elevated Pro-Inflammatory Cell-Free MicroRNA Levels in Cerebrospinal Fluid of Premature Infants after Intraventricular Hemorrhage

2020 ◽  
Vol 21 (18) ◽  
pp. 6870 ◽  
Author(s):  
Zsolt Fejes ◽  
Judit Erdei ◽  
Marianna Pócsi ◽  
Jun Takai ◽  
Viktória Jeney ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Preterm Infants ◽  
Intraventricular Hemorrhage ◽  
Inflammatory Cell ◽  
Cell Culture Supernatant ◽  
Protein Biomarkers ◽  
Choroid Plexus Epithelial Cell ◽  
Soluble Adhesion Molecules ◽  
Inflammatory Conditions

Intraventricular hemorrhage (IVH) represents a high risk of neonatal mortality and later neurodevelopmental impairment in prematurity. IVH is accompanied with inflammation, hemolysis, and extracellular hemoglobin (Hb) oxidation. However, microRNA (miRNA) expression in cerebrospinal fluid (CSF) of preterm infants with IVH has been unknown. Therefore, in the present study, candidate pro-inflammatory cell-free miRNAs were analyzed in CSF samples from 47 preterm infants with grade III or IV IVH vs. clinical controls (n = 14). miRNAs were quantified by RT-qPCR, normalized to “spike-in” cel-miR-39. Oxidized Hb and total heme levels were determined by spectrophotometry as well as IL-8, VCAM-1, ICAM-1, and E-selectin concentrations by ELISA. To reveal the origin of the investigated miRNAs, controlled hemolysis experiments were performed in vitro; in addition, human choroid plexus epithelial cell (HCPEpiC) cultures were treated with metHb, ferrylHb, heme, or TNF-α to replicate IVH-triggered cellular conditions. Levels of miR-223, miR-155, miR-181b, and miR-126 as well as Hb metabolites along with IL-8 were elevated in CSF after the onset of IVH vs. controls. Significant correlations were observed among the miRNAs, oxidized Hb forms, and the soluble adhesion molecules. During the post-IVH follow-up, attenuated expression of miRNAs and protein biomarkers in CSF was observed upon elimination of Hb metabolites. These miRNAs remained unaffected by a series of artificially induced hemolysis, which excluded red blood cells as their origin, while stimulation of HCPEpiCs with oxidized Hb fractions and heme resulted in increased extracellular miRNA levels in the cell culture supernatant. Overall, the hemorrhage-induced CSF miRNAs reflected inflammatory conditions as potential biomarkers in preterm IVH.

The in vitro action of immune pig serum on second - and third-stage Ascaris suum larvae

Parasitology ◽  
1961 ◽  
Vol 51 (3-4) ◽  
pp. 327-334 ◽  
Author(s):  
L. F. Taffs
Keyword(s):  
Excretory Pore ◽  
Animal Health ◽  
Small Degree ◽  
Immune Serum ◽  
Normal Serum ◽  
Second Stage ◽  
Third Stage ◽  
Antigenic Material ◽  
Pig Serum

Third and artificially hatched second-stage larvae of A. suum were exposed to the action of saline and normal and homologous immune pig serum. Precipitates developed at the mouth, excretory pore, anus and around the cuticle of third-stage larvae when they were placed in immune pig serum, but not in saline or normal serum. Precipitate was most evident at the excretory pore and was often the first precipitate to form. It is suggested that the excretory products may play an important role in stimulating the production of antibody in the host. A relationship was noted between the antibody titre of the serum and the amount of precipitate, the life span of the larvae, their activity, and the rate at which precipitates formed. It is concluded that the titre of the serum was in some degree a measure of the ability of the host to resist reinfection.Circumlarval precipitates did not form when second-stage larvae were placed in samples of the same immune serum. It is pointed out that this may be due to the lack of sufficient antigenic material available to react with antibody in the antisera. It is also suggested that an absence of sufficient larval antigen may also partly account for the small degree of resistance exhibited by the resistant host within the first 2 or 3 days of reinfection.The work, which is abstracted from a Ph.D. thesis, was carried out in 1957 under the tenure of an Animal Health Trust Wellcome Fellowship. I am grateful to Dr Soulsby, under whose guidance this work was carried out.

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