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 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 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.

Grafting of Choroid Plexus Ependymal Cells Promotes the Growth of Regenerating Axons in the Dorsal Funiculus of Rat Spinal Cord: A Preliminary Report

2001 ◽  
Vol 167 (2) ◽  
pp. 242-251 ◽  
Author(s):  
Chizuka Ide ◽  
Masaaki Kitada ◽  
Shushovan Chakrabortty ◽  
Masanori Taketomi ◽  
Naoya Matsumoto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Choroid Plexus ◽  
Preliminary Report ◽  
Ependymal Cells ◽  
Rat Spinal Cord ◽  
Dorsal Funiculus

Demyelination and wasting associated with polyomavirus infection in nude (nu/nu) mice

1980 ◽  
Vol 14 (4) ◽  
pp. 337-345 ◽  
Author(s):  
A. Sebesteny ◽  
Rita Tilly ◽  
Frances Balkwill ◽  
D. Trevan
Keyword(s):  
Spinal Cord ◽  
Choroid Plexus ◽  
Renal Pelvis ◽  
Inclusion Bodies ◽  
Bronchial Epithelium ◽  
Intracerebral Injection ◽  
Histopathological Changes ◽  
Wild Type ◽  
Human Tumour ◽  
Virus Particles

Nude ( nu/nu) mice bearing human tumour heterografts were affected with posterior paralysis and wasting. There was demyelination and infection of the oligodendrocytes of the spinal cord with a papovavirus. Similar virus particles and inclusion bodies were found in the bronchial epithelium, which showed histopathological changes. Similar changes were shown by the epithelia of the renal pelvis, ureter and choroid plexus. The virus was found in a transplantable human tumour, and evidence of spread by contact was also obtained. Intracerebral injection of spinal cord suspension from infected mice resulted in virus infected cutaneous carcinomata, demyelination with virus particles in the oligodendrocytes and posterior paralysis with wasting in adult nude mice. The suspension injected intraperitoneally into newborn Syrian hamsters produced tumours similar to those produced by murine polyoma. No evidence of infection was found in mice from the colony of origin. The virus was identified as murine polyoma Wild Type A2.

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 A METHOD OF SERUM TREATMENT OF PNEUMOCOCCIC SEPTICEMIA IN RABBITS

1915 ◽  
Vol 22 (4) ◽  
pp. 466-474 ◽  
Author(s):  
Carroll G. Bull
Keyword(s):  
Immune Serum ◽  
The Body ◽  
Subdural Space ◽  
Body Forces ◽  
Repeated Doses ◽  
Set Up ◽  
Number Of Bacteria ◽  
Do So

The treatment of pneumococcic septicemia in the rabbits by large doses of immune serum is detrimental, since the serum causes the formation of large clumps of bacteria in the blood which are taken out chiefly by the vessels of the lungs in which they accumulate and impede the circulation. The large doses of serum are also detrimental when they follow upon small ones through which the small clumps formed are deposited in the spleen, liver, and other organs. In this instance, the large amount of serum leads to the destruction of the pneumococci under conditions which promote an intoxication. The precise mechanism of this action is not known. The treatment of pneumococcic septicemia in rabbits by small repeated doses of immune serum can be successfully carried out. The number of pneumococci capable of being brought to destruction through phagocytosis in the organs in this way is very great. Not all the rabbits treated with small repeated doses of the serum survive. Those that succumb do so not to a general infection but to a pneumococcus meningitis. The explanation of this phenomenon is simple. When the number of pneumococci originally inoculated is very great a small number penetrate into the subdural space. Those in this space do not come under the influence of the serum, hence they are not agglutinated and prepared for phagocytosis, whence they multiply and set up a fatal meningitis. The activity of the immune serum administered in this way against virulent pneumococci is so great that a revision of our notions in the limit of powers of the anti-infectious sera seems necessary. It is patent that the problem is not simply a relation between quantity of immune bodies and number of bacteria. It is more complex than that conception indicates. The factor of the leucocytes and the degree of their possible activities under the conditions of the experiment come into play. Hereafter, in defining the mode and power of action of anti-infectious sera the condition of cooperation of the body-forces will have to be more strictly considered.

scholarly journals Differentiation of choroid plexus ependymal cells into astrocytes after grafting into the pre-lesioned spinal cord in mice

Glia ◽  
2001 ◽  
Vol 36 (3) ◽  
pp. 364-374 ◽  
Author(s):  
Masaaki Kitada ◽  
Shushovan Chakrabortty ◽  
Naoya Matsumoto ◽  
Masanori Taketomi ◽  
Chizuka Ide
Keyword(s):  
Spinal Cord ◽  
Choroid Plexus ◽  
Ependymal Cells

scholarly journals Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells

2006 ◽  
Vol 293 (2) ◽  
pp. 358-369 ◽  
Author(s):  
Noritaka Masahira ◽  
Hirohide Takebayashi ◽  
Katsuhiko Ono ◽  
Keisuke Watanabe ◽  
Lei Ding ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Ependymal Cells ◽  
Embryonic Spinal Cord

Studies on Tapeworm Physiology

1949 ◽  
Vol 26 (1) ◽  
pp. 1-15
Author(s):  
J. D. SMYTH
Keyword(s):  
Bacterial Infections ◽  
Detrimental Effect ◽  
Horse Serum ◽  
Body Cavity ◽  
The Body ◽  
Nutrient Media ◽  
Medium Strength ◽  
By Products ◽  
Histochemical Examination

1. Plerocercoid larvae of the pseudophyllidean cestode Ligula intestinalis from the body cavity of roach, were cultured in vitro at 40°C. in a variety of saline and nutrient media. About 65% of such cultures were aseptic. 2. During cultivation, larvae produced acid by-products (unidentified) and the pH fell rapidly. 3. The presence of these acid by-products slowed down development, or, if present in sufficient quantity, caused death. 4. In order to obtain development in nutrient media in a period (3 days) comparable to that required in a bird (the normal host) it was necessary to renew the medium 24-hourly. 5. 6% of the eggs produced from a worm cultured in horse serum were fertile. Fertile eggs were never obtained from larvae cultured in any other media. 6. Certain bacterial infections had no apparent detrimental effect on development, but others were toxic. 7. Some larvae underwent development in non-nutrient medium (¾ strength Locke's solution). The exact conditions under which this occurred was not determined. 8. Fragments (3 cm. long), of larvae or larvae with either scolex or posterior half removed, underwent development to the stage of oviposition in nutrient media. 9. Histochemical examination revealed that the plerocercoid larvae were almost fat-free. During cultivation, very large quantities of cytoplasmic fat were produced the quantity being proportional to the duration of cultivation. Fat was produced even under starvation conditions (i.e. during cultivation in saline) and can be considered a metabolic by-product. 10. The fresh plerocercoid contained great quantities of glycogen in the parenchyma and muscle regions. After cultivation in nutrient or saline media, considerable quantities were still present.

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