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

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.

1918 ◽  
Vol 28 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss

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.


1914 ◽  
Vol 20 (3) ◽  
pp. 249-268 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss

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.


1919 ◽  
Vol 29 (6) ◽  
pp. 597-603 ◽  
Author(s):  
Harold L. Amoss ◽  
Frederick Eberson

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.


1932 ◽  
Vol 56 (1) ◽  
pp. 13-25 ◽  
Author(s):  
Lloyd D. Felton

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.


1931 ◽  
Vol 54 (6) ◽  
pp. 859-873 ◽  
Author(s):  
S. T. Walton

These experiments show: 1. That the surface tension of normal blood serum is considerably lowered by standing undisturbed for a period of 1 hour (time-drop). 2. That the greatest time-drop recorded is with serum diluted approximately 10,000 times in fresh serum, and 50,000 times in heated serum. 3. That immune serum is not affected in the same manner by heat as is normal serum. Syphilitic serum and anti-sheep cell rabbit serum behave similarly in this respect. 4. That serum albumin is much more readily soluble in alkaline buffer solutions than globulin is, and that globulin from normal serum ionizes more than that from syphilitic serum. Further investigations are being made in an effort to determine why the proteins aggregate or dissociate under the influence of the factors under consideration.


2002 ◽  
Vol 60 (2B) ◽  
pp. 395-399 ◽  
Author(s):  
Luís R. Machado ◽  
José A. Livramento ◽  
Adelaide J. Vaz ◽  
Ednéia C. Bueno ◽  
Sylvia R. Mielli ◽  
...  

We analyzed cerebrospinal fluid (CSF) and blood serum from 55 patients with neurocysticercosis (NC) at different clinical stages. According to inflammatory activity in the CSF, three stages were identified: (1) reactive, when there was at least an increase in the number of cells; (2) weakly reactive, when significant alterations were found in the CSF, including an increase in gamma globulins, albeit without hypercytosis; (3) non-reactive, when there was neither hypercytosis nor increase in gamma globulins. Nineteen patients had the reactive form; 18 had the weakly reactive form; 18 displayed the non-reactive form. Local immunoproduction was intense in the reactive group, moderate in the weakly reactive group, and absent in the non-reactive group. The specific antibody index was raised in approximately 2/3 of patients with the reactive form, 2/3 in those with the weakly reactive form, and 1/3 in those with the non-reactive form. In conclusion: (1) the classical CSF syndrome in NC can present both in complete and partial modes; (2) local immunoproduction can occur in weakly reactive forms; (3) a raised specific antibody index can occur in the absence of an inflammatory reaction in the CSF.


1917 ◽  
Vol 25 (4) ◽  
pp. 525-537 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss

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.


1973 ◽  
Vol 30 (01) ◽  
pp. 093-105 ◽  
Author(s):  
C.H.J Sear ◽  
L Poller ◽  
F.R.C Path

SummaryThe antiheparin activity of normal serum has been studied by comparing the antiheparin activities of sera obtained from normal whole blood, platelet-rich plasma and platelet-’free’ plasma with a purified platelet extract during differential isoelectric precipitation and by gel filtration chromatography.The mean values for the activity of PRP-serum and PFP-serum were 106% (S.D. 11) and 10% (S.D. 3) of untreated whole blood respectively. The activity of whole blood serum, PRP serum and whole blood serum plus platelet extract precipitated under identical physical conditions, i.e. pH 7.0, I =0.008, indicating that the activities of the three samples are probably associated with PF4. PF4 precipitated from human platelet extract at pH 4.0, but this is probably due to the difference in the two biochemical environments investigated, i.e. serum and platelet extract.The gel filtration experiments revealed striking similarities between the major antiheparin activities of serum and platelet extract. At physiological pH and ionic strength both activities were associated with high molecular weight material, but at physiological pH and elevated ionic strength both activities behaved as much smaller entities of molecular weight between 25,000 and 30,000 daltons and it seems very likely that both activities are associated with the same molecule, i.e. PF4.


2021 ◽  
Vol 70 (5) ◽  
pp. 23-36
Author(s):  
Ekaterina A. Kondratyeva ◽  
Alina O. Ivanova ◽  
Maria I. Yarmolinskaya ◽  
Elena G. Potyomkina ◽  
Natalya V. Dryagina ◽  
...  

BACKGROUND: Consciousness is the state of being awake and aware of oneself and the environment. The disorders of consciousness result from pathologies that impair awareness. The development of effective comprehensive personalized interventions contributing to the recovery of consciousness in patients with chronic disorders of consciousness is one of the most pressing and challenging tasks in modern rehabilitation. AIM: The aim of this study was to understand structural problems of the pituitary gland, blood levels of gonadotropins and melatonin as well as brain damage markers in the blood and cerebrospinal fluid in patients with chronic disorders of consciousness and to analyze the levels of the above markers among different groups of patients depending on the level of impaired consciousness. MATERIALS AND METHODS: We examined 61 chronic disorders of consciousness patients and identified three groups depending on the level of consciousness including 24 patients with unresponsive wakefulness syndrome, 24 patients with a minus minimally conscious state, and 13 patients with minimally conscious state plus. We performed magnetic resonance imaging of chiasmatic-sellar region and determined blood serum levels of follicle-stimulating and luteinizing hormones and melatonin, as well as urinary level of 6-sulfatoxymelatonin and the content of brain derived neurotrophic factor (BDNF), apoptosis antigen (APO-1), FasL, glutamate, and S100 protein in the blood serum and cerebrospinal fluid. RESULTS: The patients were examined in the age ranging from 15 to 61 years old. Patient groups were homogeneous by the level of consciousness in terms of age and duration of chronic disorders of consciousness by the time of examination. The patients did not differ in the pituitary volume regardless of the level of consciousness. No significant differences were found between the groups with different levels of consciousness when studying the levels of melatonin in the blood serum and its metabolite in the urine. A peak in melatonin secretion was detected at 3 a.m. in 54.5 % of the patients, which can be considered as a favorable prognostic marker for further recovery of consciousness. Hypogonadotropic ovarian failure was found in 34 % of the patients, with normogonadotropic ovarian failure in the remaining patients. Serum APO-1 and BDNF levels were significantly higher in patients with minimally conscious state relative to those with unresponsive wakefulness syndrome. Significantly lower levels of glutamate in the cerebrospinal fluid were detected in women with unresponsive wakefulness syndrome compared to patients with minimally conscious state. CONCLUSIONS: Further in-depth examination and accumulation of data on patients with chronic disorders of consciousness may provide an opportunity to identify highly informative markers for predicting outcomes and to develop new effective approaches to rehabilitation of consciousness in this category of patients.


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