scholarly journals The Active Immunization of Guinea-Pigs Passively Immunized with Homologous Antitoxic Serum

1955 ◽  
Vol 53 (2) ◽  
pp. 172-179 ◽  
Author(s):  
J. H. Mason ◽  
Mary Robinson ◽  
P. Agerholm Christensen
Keyword(s):  
Guinea Pigs ◽  
Diphtheria Toxin ◽  
Active Immunization ◽  
The Other ◽  
Control Groups ◽  
Large Measure ◽  
Primary Stimulus ◽  
Serum Titre ◽  
Secondary Stimulus

SummaryGroups of guinea-pigs were passively immunized against diphtheria toxin with homologous antitoxic serum so that their sera contained, at the start of the experiment, 1·0, 0·1, 0·01 or 0·001 unit/ml, respectively. They were then actively immunized with one, or two spaced, injections of 0·1 Lf of A.D.F. Two control groups were included, one passively immunized only and the other actively immunized only.Passively produced serum titres of 0·01 and 0·001 unit/ml. did not interfere with active immunization in any demonstrable way.A titre of 0·1 unit/ml. did interfere with active immunization, markedly 4 weeks after the primary, slightly 2 weeks after the secondary, and markedly 14 weeks after the secondary, stimulus.A titre of 1·0 unit/ml. interfered with active immunization, markedly 4 weeks after the primary, and 2 and 14 weeks after the secondary, stimulus. This titre, however, did not completely annul the effect of the primary stimulus. The highest observed serum titre was obtained at the 32nd, instead of at the 4th week, as in the guinea-pigs actively immunized only.In large measure the results confirm those of Barr and her colleagues who found that, in human babies, an initial ‘passive’ titre of 0·04 unit/ml. serum did not interfere with active immunization, whereas a titre of 0·1 unit/ml, led to unsatisfactory immunization.

scholarly journals The Schick Dose of Diphtheria Toxin as a Secondary Stimulus

1922 ◽  
Vol 21 (1) ◽  
pp. 104-111 ◽  
Author(s):  
A. T. Glenney ◽  
K. Allien
Keyword(s):  
Guinea Pig ◽  
Positive Reaction ◽  
Guinea Pigs ◽  
Diphtheria Toxin ◽  
Primary Stimulus ◽  
Active Immunity ◽  
G 21 ◽  
Detectable Quantity ◽  
G 34 ◽  
Secondary Stimulus

The injection of the small amount of diphtheria toxin used in the Schick test may act as a secondary stimulus.A Schick test may therefore cause a great and rapid increase in the immunity of the animals tested.Examples are quoted of six rabbits and twelve guinea-pigs in Tables II to VII.2. A fraction of a Schick dose may act as a secondary stimulus. Rabbit G 23 quoted in Table IV, injected with 1/10 of a Schick dose, showed an immunity response, the antitoxic content of its blood rising from 1/50 to nearly 1/10 unit per c.c. in six days.3. The action of a Schick dose as a secondary stimulus may cause an animal to give a negative reaction when tested seven days or more after the first positive reaction.This is illustrated by rabbits G 7 in Table III, G 31 in Table II, G 32 and G 34 in Table V and four guinea-pigs in Table VI.4. The antigenic value of a Schick dose of toxin as a secondary stimulus may be as high as that of a reasonable dose of a toxin-antitoxin mixture suitable for human immunisation. Examples are given comparing the results of the injection of a Schick dose of toxin and of a toxin-antitoxin mixture in the same rabbit in Table III, in different rabbits, G 20 and G 22 in Table IV and reference is made to the companion rabbits to those quoted in Table V.5. The antigenic value of a Schick dose as a secondary stimulus can be demonstrated:A. In animals which have not produced a detectable quantity of antitoxin (that is less than 1/2000 of a unit per c.c.) as the result of a primary stimulus.See both rabbits in Table II, rabbit G 20 in Table IV, both rabbits in Table V, and guinea-pig FF 19. v in Table VII. The four guinea-pigs in Table VI probably come under the same heading.B. In animals whose actively produced antitoxin has fallen below a de tectable level.See rabbit G 7 in Table III.(These results add further confirmation to the phenomenon reported in the paper “Active immunity to diphtheria in the absence of detectable antitoxin” (Glenny and Allen, 1922).6. A Schick dose of toxin which gives a positive reaction may, by acting as a secondary stimulus, produce a rapid increase in the antitoxic value of animals already containing some actively produced antitoxin.See guinea-pig LL 17. vi in Table VII.7. A Schick dose of toxin which causes no reaction may, by acting as a secondary stimulus, produce a rapid increase in the antitoxic value of animals already containing some actively produced antitoxin.See guinea-pigs in Table VII.8. A Schick dose of toxin may fail as a secondary stimulus if the antitoxic content at the time of injection is comparatively high.See rabbit G 21 in Table IV.

scholarly journals CARRIER FUNCTION IN ANTI-HAPTEN IMMUNE RESPONSES

1970 ◽  
Vol 132 (2) ◽  
pp. 261-282 ◽  
Author(s):  
David H. Katz ◽  
William E. Paul ◽  
Edmond A. Goidl ◽  
Baruj Benacerraf
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Guinea Pigs ◽  
Association Constant ◽  
Gamma Globulin ◽  
Active Immunization ◽  
Antibody Responses ◽  
The Other ◽  
Immunoglobulin Class ◽  
Freund's Adjuvant

Preimmunization of either guinea pigs or rabbits to bovine gamma globulin (BGG) prepares the animals for markedly enhanced antibody responses to 2,4-dinitrophenyl-BGG (DNP-BGG). This phenomenon is observed both in the primary anti-DNP antibody response to DNP-BGG and in the secondary anti-DNP antibody response to DNP-BGG in animals primed with DNP-ovalbumin (DNP-OVA). The BGG preimmunization is most effective if the antigen is administered as a complete Freund's adjuvant emulsion; in rabbits, a dose of 1 µg of BGG is more effective than a dose of 50 µg, whereas the reverse is true in guinea pigs. Transfusion of homologous anti-BGG sera fails to replace active immunization with BGG in the preparation of animals for these enhanced anti-DNP antibody responses. Both the immunoglobulin class and the average association constant for ϵ-DNP-L-lysine of the anti-DNP antibody produced in these enhanced responses is determined by the mode and time of immunization with haptenic conjugates and is not appreciably influenced by the nature of the carrier preimmunization. These studies indicate that the carrier specificity of hapten-specific anamnestic antibody responses is largely due to the interaction of two independent cell associated recognition units, one specialized for carrier and the other specific for haptenic determinants.

scholarly journals Notes on the Production of Immunity to Diphtheria Toxin

1921 ◽  
Vol 20 (2) ◽  
pp. 176-220 ◽  
Author(s):  
A. T. Glenny ◽  
H. J. Südmersen
Keyword(s):  
Latent Period ◽  
Diphtheria Toxin ◽  
Single Injection ◽  
Passive Immunity ◽  
Primary Stimulus ◽  
Immunity Response ◽  
Striking Contrast ◽  
Secondary Stimulus

(a) Primary Stimulus. In animals possessing no normal antitoxin a single injection of toxin either “attenuated” or under cover of antitoxin, whether injected previously or at the same time or present in the form of passive immunity maternally transmitted, is followed by a latent period of about three weeks, and the maximum immunity is reached in about eight weeks.(b) Secondary Stimulus. In immune animals, whether naturally immune or artificially immunised, a single injection of toxin or of a toxin-antitoxin mixture is followed by a latent period of about four days and the maximum immunity is reached in about ten days; the great and rapid immunity response to the secondary stimulus offers a striking contrast to the small and gradual response to the primary stimulus.(c) Intermediate Stimulus. In partially immune animals the response to an injection of toxin is in magnitude and rapidity of a character intermediate between the responses following a primary and a secondary stimulus.

Hepatocyte Alterations in Guinea Pigs FED Polychlorinated Biphenyls (PCBs), Dibenzodioxins (PCDD), AND DIBENZOFURANS (PCDF)

1982 ◽  
Vol 40 ◽  
pp. 56-57
Author(s):  
J. N. Turner ◽  
D. N. Collins
Keyword(s):  
Guinea Pigs ◽  
Room Temperature ◽  
Dose Group ◽  
Methyl Cellulose ◽  
Uranyl Acetate ◽  
Target Organ ◽  
Office Building ◽  
Lead Citrate ◽  
Control Groups ◽  
Cooling Fluid

A fire involving an electric service transformer and its cooling fluid, a mixture of PCBs and chlorinated benzenes, contaminated an office building with a fine soot. Chemical analysis showed PCDDs and PCDFs including the highly toxic tetra isomers. Guinea pigs were chosen as an experimental animal to test the soot's toxicity because of their sensitivity to these compounds, and the liver was examined because it is a target organ. The soot was suspended in 0.75% methyl cellulose and administered in a single dose by gavage at levels of 1,10,100, and 500mgm soot/kgm body weight. Each dose group was composed of 6 males and 6 females. Control groups included 12 (6 male, 6 female) animals fed activated carbon in methyl cellulose, 6 males fed methyl cellulose, and 16 males and 10 females untreated. The guinea pigs were sacrificed at 42 days by suffocation in CO2. Liver samples were immediately immersed and minced in 2% gluteraldehyde in cacadylate buffer at pH 7.4 and 4°C. After overnight fixation, samples were postfixed in 1% OsO4 in cacodylate for 1 hr at room temperature, embedded in epon, sectioned and stained with uranyl acetate and lead citrate.

scholarly journals A SOLUBLE ANTIGEN OF LYMPHOCYTIC CHORIOMENINGITIS

1940 ◽  
Vol 72 (4) ◽  
pp. 389-405 ◽  
Author(s):  
J. E. Smadel ◽  
M. J. Wall
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Lymphocytic Choriomeningitis ◽  
The Other ◽  
Soluble Antigen ◽  
Soluble Substance ◽  
Other Hand ◽  
The Times

Anti-soluble substance antibodies and neutralizing substances, which develop following infection with the virus of lymphocytic choriomeningitis, appear to be separate entities. The times of appearance and regression of the two antibodies are different in both man and the guinea pig; the antisoluble substance antibodies appear earlier and remain a shorter time. Moreover, mice develop them but no demonstrable neutralizing substances. Injection of formalin-treated, virus-free extracts containing considerable amounts of soluble antigen fails to elicit anti-soluble substance antibodies and to induce immunity in normal guinea pigs; administration of such preparations to immune pigs, however, is followed by a marked increase in the titer of anti-soluble substance antibodies in their serum. On the other hand, suspensions of formolized washed virus are effective in normal guinea pigs in stimulating both anti-soluble substance antibodies and protective substances, and in inducing immunity to infection.

scholarly journals Using historical data to facilitate clinical prevention trials in Alzheimer disease? An analysis of longitudinal MCI (mild cognitive impairment) data sets

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Manfred Berres ◽  
Andreas U. Monsch ◽  
René Spiegel
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Performance ◽  
Placebo Treatment ◽  
Drug Trial ◽  
The Other ◽  
Data Sets ◽  
Control Groups ◽  
Community Needs ◽  
Clinical Prevention

Abstract Background The Placebo Group Simulation Approach (PGSA) aims at partially replacing randomized placebo-controlled trials (RPCTs), making use of data from historical control groups in order to decrease the needed number of study participants exposed to lengthy placebo treatment. PGSA algorithms to create virtual control groups were originally derived from mild cognitive impairment (MCI) data of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. To produce more generalizable algorithms, we aimed to compile five different MCI databases in a heuristic manner to create a “standard control algorithm” for use in future clinical trials. Methods We compared data from two North American cohort studies (n=395 and 4328, respectively), one company-sponsored international clinical drug trial (n=831) and two convenience patient samples, one from Germany (n=726), and one from Switzerland (n=1558). Results Despite differences between the five MCI samples regarding inclusion and exclusion criteria, their baseline demographic and cognitive performance data varied less than expected. However, the five samples differed markedly with regard to their subsequent cognitive performance and clinical development: (1) MCI patients from the drug trial did not deteriorate on verbal fluency over 3 years, whereas patients in the other samples did; (2) relatively few patients from the drug trial progressed from MCI to dementia (about 10% after 4 years), in contrast to the other four samples with progression rates over 30%. Conclusion Conventional MCI criteria were insufficient to allow for the creation of well-defined and internationally comparable samples of MCI patients. More recently published criteria for MCI or “MCI due to AD” are unlikely to remedy this situation. The Alzheimer scientific community needs to agree on a standard set of neuropsychological tests including appropriate selection criteria to make MCI a scientifically more useful concept. Patient data from different sources would then be comparable, and the scientific merits of algorithm-based study designs such as the PGSA could be properly assessed.

scholarly journals EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS

1930 ◽  
Vol 51 (5) ◽  
pp. 769-776 ◽  
Author(s):  
Max B. Lurie
Keyword(s):  
Guinea Pigs ◽  
Wire Mesh ◽  
The Other ◽  
Tuberculous Infection ◽  
Source Of Infection ◽  
Natural Modes ◽  
The Difference ◽  
The One ◽  
Portal Of Entry ◽  
Human Autopsy Material

Under conditions closely simulating the natural modes of tuberculous infection in man normal guinea pigs have acquired tuberculosis by being exposed under two degrees of crowding to tuberculous cage mates in ordinary cages, where the food became soiled with excreta, bearing tubercle bacilli, and in special cages, with wire-mesh floors, where this source of infection was almost entirely eliminated. Guinea pigs were also exposed in the same room but not in the same cage with tuberculous animals. It was found that the relative tuberculous involvement of the mesenteric and tracheobronchial nodes showed a gradation of change from an almost completely alimentary infection to a completely respiratory infection. The disease involved the mesenteric nodes predominantly in the crowded ordinary cages, with much less or no affection of the tracheobronchial nodes. It was similarly, but less markedly, enteric in origin in the less crowded ordinary cages, the mesenteric nodes again being larger than the tracheobronchial nodes, but the difference in size was not so great. In the more crowded special cages the relative affection of these two groups of nodes alternated, so that in some the mesenteric, in some the tracheobronchial nodes were more extensively tuberculous. A disease characterized by less or no affection of the mesenteric nodes and by extensive lesions of the tracheobronchial nodes was seen in the less crowded special cages. Finally there was a massive tuberculosis of the tracheobronchial nodes with usually no affection of the mesenteric nodes in the frankly air-borne tuberculosis acquired by guinea pigs exposed in the same room but not to tuberculous cage mates. This gradation in the rô1e played by the enteric and respiratory routes of infection, as first the one and then the other becomes the more frequent channel of entrance for tuberculosis, would indicate that the penetration of tubercle bacilli by the one portal of entry inhibits the engrafting of tuberculosis in the tissues by way of the other portal of entry. It is apparent that in the special cages the opportunities for inhaling tubercle bacilli are at most equal to if not much less than in the ordinary cages; for in the latter dust from the bedding, laden with tubercle bacilli, is stirred up almost constantly by the animals, whereas in the special cages there is no bedding at all, and therefore, presumably, no more tubercle bacilli in the air than may occur in any part of the room. Nevertheless the route of infection was predominantly the respiratory tract in the special cages, especially in the less crowded, apparently because the enteric route had been largely eliminated. The greater predominance of the respiratory route amongst guinea pigs that acquired tuberculosis in the less crowded ordinary cages as compared to the lesser significance of this route in the more crowded ordinary cages would point in the same direction. These observations are in harmony with our knowledge that tuberculosis once implanted in an organism confers a certain degree of immunity to the disease. It is noteworthy that in a study of human autopsy material Opie (3) has found that when healed lesions are present in the mesentery focal tuberculosis in the lungs is seldom found, and that when first infection occurs by way of the lungs it tends to prevent the engrafting of the disease by way of the intestinal tract.

scholarly journals THE PATHOLOGIC EFFECTS OF STREPTOCOCCI FROM CASES OF POLIOMYELITIS AND OTHER SOURCES

1917 ◽  
Vol 25 (4) ◽  
pp. 557-580 ◽  
Author(s):  
Carroll G. Bull
Keyword(s):  
Spinal Cord ◽  
Guinea Pigs ◽  
The Other ◽  
Laboratory Animals ◽  
Histological Changes ◽  
Other Hand ◽  
Brain And Spinal Cord ◽  
The Brain

Streptococci cultivated from the tonsils of thirty-two cases of poliomyelitis were used to inoculate various laboratory animals. In no case was a condition induced resembling poliomyelitis clinically or pathologically in guinea pigs, dogs, cats, rabbits, or monkeys. On the other hand, a considerable percentage of the rabbits and a smaller percentage of some of the other animals developed lesions due to streptococci. These lesions consisted of meningitis, meningo-encephalitis, abscess of the brain, arthritis, tenosynovitis, myositis, abscess of the kidney, endocarditis, pericarditis, and neuritis. No distinction in the character or frequency of the lesions could be determined between the streptococci derived from poliomyelitic patients and from other sources. Streptococci isolated from the poliomyelitic brain and spinal cord of monkeys which succumbed to inoculation with the filtered virus failed to induce in monkeys any paralysis or the characteristic histological changes of poliomyelitis. These streptococci are regarded as secondary bacterial invaders of the nervous organs. Monkeys which have recovered from infection with streptococci derived from cases of poliomyelitis are not protected from infection with the filtered virus, and their blood does not neutralize the filtered virus in vitro. We have failed to detect any etiologic or pathologic relationship between streptococci and epidemic poliomyelitis in man or true experimental poliomyelitis in the monkey.

Geography and the Gerrymander

1918 ◽  
Vol 12 (3) ◽  
pp. 403-426 ◽  
Author(s):  
C. O. Sauer
Keyword(s):  
Public Opinion ◽  
Major Part ◽  
The Other ◽  
European Countries ◽  
Large Measure ◽  
Adequate Knowledge ◽  
Other Hand ◽  
Partial Suppression ◽  
Historical Basis ◽  
The Individual

The gerrymander is an American name for a political abuse, which, though by no means exclusively American, has been most widely practiced and generally tolerated in this country. It is a device for the partial suppression of public opinion that simulates agreement with democratic institutions. The subterfuge, therefore, has no place in countries in which oligarchic control is legitimized. Nor is it suited to European conditions, because it is difficult there to shift electoral boundaries. European electoral units in large part have a clearly defined historical basis, which in turn rests upon geographic coherence. This solidarity is commonly so great that it cannot be disregarded. American political divisions on the other hand show in major part very imperfect adjustment to economic and historic conditions, largely, because many of the divisions were created in advance of such conditions. They are, in the main, not gradual growths, but deliberate and arbitrary legislative creations, made without adequate knowledge of the conditions that make for unity or disunity of population within an area. Political divisions tend, therefore, to be less significant than in European countries and to be regarded more lightly. It is in particular the smaller unit, such as the county, that has been manipulated for electoral purposes. In spite of their poorly drawn individual boundaries, groups of counties can be organized into larger electoral units in such a manner as to represent a common body of interests predominating. On the other hand they can be so arranged as to mask these interests. The lack of proper coherence in the individual county may be rectified in large measure in the group, or it may be intensified. Gerrymandering accomplishes the latter result.

ANTIBIOTICS AND IATROGENIC DISEASE

PEDIATRICS ◽  
1958 ◽  
Vol 22 (1) ◽  
pp. 164-170
Author(s):  
T. E. Roy
Keyword(s):  
Fatal Outcome ◽  
Light Therapy ◽  
Drug Dose ◽  
Iatrogenic Disease ◽  
The Other ◽  
Clinical Use ◽  
Large Measure ◽  
Calculated Risk ◽  
Severe Infections ◽  
The Subject

THE ASSOCIATION of the term "iatrogenic disease" with the clinical use of antibiotics poses many problems. Physicians generally are familiar with most of the untoward reactions that may follow the use of antibiotics, and many excellent reviews of the subject are to be found in the literature. One cannot divorce the undesirable effects of antibiotics from the beneficial ones and, in this light, therapy becomes a calculated risk. If the probable discomforts or dangers outweigh the probable advantages, the cure may be worse than the disease, and one is then dealing with true iatrogenic disease. Probabilities of this kind cannot be assessed easily with antibiotics because reactions vary so much with type of drug, dose, course, method of giving and in different patients. Certain reports may be biased one way or the other because of personal prejudices or unusual series. Some ill effects are undoubtedly related to unwise, improper or careless use of the drug; others are not. So true incidences are not accurately known. Reactions where antibiotics are being used needlessly for trivial infections or for unnecessary prophybaxis are particularly deplorable while risks are justified when dealing with severe infections known to respond. Evaluation is difficult with infections of borderline severity and those prone to exceptionally severe secondary bacterial complications. Reactions may be mild or severe; none is negligible. Oxytetracycline, for example, is considered to be relatively harmless. Still, Jackson and his colleagues reported that 58% of patients with pneumonia showed untoward effects attributable to this antibiotic. Most reactions were mild, but the antibiotic was believed to have contributed in large measure to the fatal outcome in five of the seven patients who died in the 91 cases.

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