Fall In Titer Research Articles

Evaluation of rosette inhibition test in renal transplantation.

Serial rosette inhibition tests were performed on 11 renal transplant patients in an attempt to predict graft rejection. The rosette inhibition titre was higher in immunosuppressed patients than in normal subjects. The test was of predictive value in only two out of 12 rejection episodes, where a fall in titre to normal levels occurred 48 hours and 24 hours, respectively, before biochemical evidence of rejection. In two further rejection episodes the titre fell at the time of rejection. The titre changes in all tests were small and there were frequent inconsistencies in the results of individual tests. A study of the variables was undertaken, with standardization of the technique, and improvements were made in reading the test. Despite these changes the test was still not sufficiently accurate or reliable to be used as the basis of treatment of rejection episodes.

Evaluation of Streptozyme and Antistreptolysin O Tests in Streptococcal Pyodermal Nephritis

The evaluation of the streptozyme test in sera from 34 patients with streptococcal pyodermal nephritis was studied. Ninety-seven percent of the patients developed high titers of antistreptozyme antibodies on the first bleeding after hospitalization, in contrast to only 40% of patients who developed elevated antistreptolysin O titers. The high antistreptozyme titers declined during convalescence and reached normal levels in the sixth month after onset of the disease. The most significant fall in titers occurred between 1 and 2 months from the onset of disease. The streptozyme test may be particularly helpful as a rapid screening test for antibodies in streptococcal pyodermal nephritis.

The Effects of Killing or Removal of Animals Affected with Foot-and-Mouth Disease on the Amounts of Airborne Virus Present in Looseboxes

Pigs or cattle which had been infected with foot-and-mouth disease virus were held in looseboxes and the amount of virus present in the air after killing or removal of the animals was measured. Killing or removal of pigs led to a reduction of twenty-five fold or more in virus recovered but virus persisted in the looseboxes for at least 24 hours although only to 1/5000th of that originally present. Removal of cattle from the box did not lead to any significant fall in virus recovery. Epithelium was collected from lesions on pigs’ feet at intervals up to 24 hours after killing, but no fall in titre was found. These results are discussed in relation to the source of airborne virus from the animal, and to the measures taken in the field in the control of disease by slaughter. Les cochons ou le bétail infectés par le virus de la fièvre aphteuse étaient gardés dans des box et on a mesuré la quantité de virus presents dans l’air après abbatage ou enlèvement des animaux. L’abattage ou l’enlèvement des cochons provoquait une réduction de 25 fois ou plus du nombre de virus mais les virus persistaient dans les box 24 heures au moins quoiqu’à raison de 1/5000 ème seulement de ceux présents à l’origine. L’enlèvement du bétail du box ne provoqua aucune diminution significative de la quantité de virus récupérés. On préleva l’épithelium des lésions des pieds de cochons à intervalles allant jusqu’à 24 heures après abattage, mais on ne constata aucune diminution du titre. Ces résultats sont discutés par rapport à la source de virus d’origine atmosphèrique provenant de l’animal et en fonction des mesures prises au champ pour contrôler la maladie par abattage. Schweine oder Rinder, die mit Maul- und Klauenseuche-Virus infiziert waren, wurden in “loose-boxes” gehalten und die Menge der in der Luft suspendierten Viren nach Schlachtung oder Entfernung der Tiere gemessen. Schlachtung oder Entfernung von Schweinen führte zu einer 25 fachen oder grösseren Verminderung der Virusmenge, doch waren Viren in den “loose-boxes” für wenigstens 24 Stunden nachweisbar, obwohl nur in 1/5000 der ursprünglichen Menge. Entfernung von Rindern führte zu keiner signifikanten Verminderung der gefundenen Viren. Von erkrankten Stellen an den Füssen der Schweine wurde Epithel entnommen, bis zu 24 Stunden nach der Schlachtung, doch wurde keine Verminderung des Titers gefunden. Diese Ergebnisse werden in Beziehung auf die in der Luft suspendierten Viren und ihre Herkunft von den Tieren erörtert. Die vorbeugenden Massnahmen gegen die Krankheut in Form von Tötung der Tiere werden besprochen. Los cerdos y ganado vacuno que habían sido infectados por los virus de la fiebre aftosa fueron mantenidos en sus establos y se procedió a la medida de virus presentes en el aire después de sacrificar ο retirar a los animales de dichos establos. El sacrificio ο retirada de los cerdos condujo a una reducción del orden del 25 por ciento ó más de los virus recogidos, aunque los virus persistieron en los establos por lo menos durante 24 horas, aunque sólo a 1/5000 de las cifras originales. La retirada del ganado vacuno de los establos no condujo a ninguna reducción significativa en la recogida de virus. Se recogieron muestras del epitelio procedente de lesiones en las patas de los cerdos a intervalos de 24 horas después de haber sacrificado a los animales, sin obtenerse ninguna reducción en el título. Se discuten estos resultados en relación al origen de los virus aereos procedentes de los animales y a las medidas tomadas en el campo en el control de la enfermedad por el sacrificio de los animales.

Serological Diagnosis of Fowl Spirochetosis

SUMMARY An almost pure particulate spirochetal antigen was prepared for the macroplate-agglutination reaction. The antigen did not react with sera of apparently healthy birds, nor did it cross-agglutinate with immune sera against fowl pox and coccidiosis. The antigen was stable for three months at room temperature. Agglutinins first appeared in the sera on the 4th day of infection, reaching a peak titer of 1:156.4 on 11th day. This titer was maintained to the 27th day, and then declined rapidly to 1:17.8 by the 58th day. The fall in titer thereafter was slow, reaching 1:6.7 by the 152nd day.

Ihalation, persistence and dispersal f foot-and-mouth disease virus by man.

Sampling of human subjects, who had been in contact with animals infected with foot-and-mouth disease (FMD) virus, showed that virus could be recovered from the nose, throat, saliva and from air expelled during coughing, sneezing, talking and breathing. The amounts of virus recovered paralleled those collected with a large-volume sampler and multistage impinger and these findings confirmed that the highest recovery of airborne virus was from infected pigs followed by cattle and sheep. More virus was found in the noses of those examining infected animals than in those operating the samplers, but there was variation between the subjects. In the majority there was a 1.8 log fall in titre by 3.5 hr., but virus persisted in the nose of one subject for 28 hr. Nose blowing or washing the nostrils did not remove virus completely, nor were cloth or industrial masks completely effective in preventing inhalation of virus. It was possible to transmit virus from infected subjects to others on one occasion. No clinical cases of FMD in man resulted from exposure, nor was there any rise in antibody. Use was made of these findings in determining sites of aerosol excretion in animals, and the results are discussed in relation to FMD in man and to the spread of respiratory viruses by the airborne route.

Characteristics of the Serum Vibriocidal and Agglutinating Antibodies in Cholera Cases and in Normal Residents of the Endemic and Non-Endemic Cholera Areas

Abstract Vibriocidal and agglutinating antibodies in sera from acute cholera cases, normal residents of endemic and non-endemic cholera areas and maternal and cord blood were characterized by 2-mercaptoethanol (2-ME) sensitivity and density gradient fractionation. In acute cholera there was a rapid and parallel rise in whole serum and 2-ME-resistant vibriocidal and agglutinating antibodies, peaking in 7 to 10 days, and then a parallel fall in titers in whole serum and 2-ME-resistant antibodies. Density gradient studies confirmed this pattern, demonstrating the rise and fall of vibriocidal and agglutinating titers in both the IgM and IgG-IgA fractions. The apparent independence of the vibriocidal and agglutinating activity in the IgG-IgA fractions suggested that IgA as well as IgG might be contributing to the agglutinating titers. The presence of vibriocidal and agglutinating titers on admission in many adult cholera cases, coupled with a rapid rise in IgG antibody, indicates that this is a secondary response in individuals already primed by natural infection or cholera vaccine. Most residents of the endemic cholera area (East Pakistan) had high vibriocidal and agglutinating titers with activity in both IgM and IgG, in contrast to sera from residents of non-endemic areas (U. S. A. and Czechoslovakia) who had non-detectable or low titers with vibriocidal activity in most cases exclusively in IgM. Transplacental transfer of IgG vibriocidal antibody was demonstrated.

Secondary antibody-forming potential of mice in relation to age—Its significance in senescence

A primary antibody response profile analogous to a damped harmonic motion was observed when BC3F1 mice were injected i.p. with 1.5 × 10 8 rat red blood corpuscles when they were 1 month old and their agglutinin response was followed throughout their life-span. There were six cycles of rise and fall in titer, and the length of each in sequence was 3, 23, 24, 16, 24, and 16 weeks. The spleen cell mass, indicative of the total number of cells per spleen, increased exponentially between 1 week and 2 months after birth with a T 2 of ∼1 month and then increased gradually throughout the life-span. The primary antibody-forming potential (PAFP) per spleen increased 10-fold to a maximum level between 1 and 4 months of age, remained at this level for the next 3–4 months, and then decreased slowly in apparently an exponential manner with a T 1 2 of ∼10 months until at least 31 months of age. When 1-month-old mice were primed with an adequate dose of antigen their secondary antibody-forming potential (SAFP) per spleen increased 32-fold during the first week after priming and another 3-fold to a maximum level during the subsequent 3 months. It then decreased in an apparently exponential manner with a T 1 2 of ∼10 months until at least 27 months of age. The SAFP per mouse also increased rapidly during the first month after priming and then slowly during the next 2 months to a maximum level. During this interval the SAFP per mouse increased 25-fold in contrast to a 100-fold increase in the SAFP per spleen. The SAFP per mouse remained at this maximum level for the next 2–4 months before it too began to decrease exponentially with a T 1 2 of 6 months until at least 27 months of age. The results are discussed in terms of a change in immunologically competent cells and homeostatic factors regulating the expression of these cells. A brief discussion is also made of the significance of senescence of immune potential to the life expectancy of an individual.

Serologic Tests for Arizona Group Infections

Agglutination tests have been used by several researchers for the detection of Arizona group (AG) carrier turkeys. Hinshaw and McNeil (9) reported that survivors from AG infection at the poult age reacted to 0 or H agglutination with very low frequency. Frequency of Arizona isolation was considerably higher among reactors necropsied (8). Goetz (7) used H agglutination for the detection of carrier birds. The present authors found well developed agglutinins of both somatic and flagellar types in inoculated turkeys, but the levels decreased rapidly. Naturally infected birds had the same tendency toward a rapid fall in titer of agglutinins. Within 14 weeks, the tendency was more evident in H agglutinins. Almost all birds observed had no H agglutinins after surviving systemic infection, even though the birds harbored AG (unpublished data). This study was done primarily to determine the character of agglutinins, especially 0 agglutinins, for AG in turkeys. In addition, indirect hemagglutination and antiglobulin tests were investigated to determine if these procedures were more sensitive than the standard saline test.

Autoimmune Hemolytic Anemia in NZB/B1 Mice Treated with the Corticosteroid Drug Betamethasone

Abstract A controlled therapeutic trial of the corticosteroid drug betamethasone phosphate in the autoimmune hemolytic anemia of the NZB/Bl inbred strain of mice is described. In the treated group, in contrast to the controls, anemia was improved, positive Coombs tests became weaker or negative and there was a fall in titer of circulating antibody. The similarity of this disease in the mouse and in man is discussed. It is concluded that the NZB/Bl mice will prove useful in investigating the effectiveness and mode of action of therapeutic agents in autoimmune hemolytic anemia.

Blood groups and abortions

Although fetal loss has an established relationship to ABO incompatibility, the question has been whether the loss is due to infertility or to abortion. The hypothesis has been presented that the outcome of an incompatible pregnancy is determined by the mother's antibody titer. As a first step in testing this hypothesis, blood groups of aborted tissues were tested. A distribution of blood groups of the aborted tissues different from that of the general population would imply that ABO incompatibility is a factor in abortion. A method has been described whereby tissue ABO antigens can be identified in secretors. Tissue antigens agglutinate the corresponding antibodies from serum of known titer: a fall in titer indicates the blood group of the tissue. Testing of the fetal side of the placenta appears to give the blood group of the fetus. Analysis of results for whites and Negroes showed an unusually large proportion of abortuses having B antigen, supporting the hypothesis that ABO incompatibility is a cause of spontaneous abortion. Analysis of 27 mother-abortus pairs showed a relatively large proportion to be ABO incompatible. Particularly outstanding was the large number of incompatibilities due to antigen B, a finding which may contribute to the concept of balanced polymorphism of blood groups.

Studies on Enteroviruses of the Pig: VII.—Some Properties of a Porcine Enterovirus (F7)

A porcine enterovirus (F7) grew and produced cytopathic effects in cultures of pig cells. In the supernatant fluid of infected pig-kidney tissue cultures a rapid increase of virus titre was found between 10 and 20 hours after infection; peak titres were reached between 50 and 70 hours after infection. Filtration studies indicated that the diameter of the virus was about 3.5mμ. It was resistant to ether and to sodium desoxycholate. Ninety per cent of the virus was inactivated by 0.009 per cent formaldehyde at 36°C. in 13 hours, and by ultra-violet irradiation at an intensity of 99 μ watts/cm.2 in 0.8 minute. The virus was stable for periods of 42 to 67 days when stored in buffered solutions having pH values beween 4 and 9. No fall in titre was detected after storage for 650 days at −70°C. At 4°C., 36°C. and at room temperatures the 90 per cent inactivation times were 393, 4.3 and 51.3 days respectively. At 56°C. the 90 per cent inactivation time was 5.3 minutes, but some virus persisted for more than 1 hour. No virus was detected after heating at 65°C. for 2 minutes. Nineteen young pigs were inoculated by the intracerebral, intravenous or oral and intranasal routes with tissue culture fluid containing F7 virus. No clinical signs of infection were observed, but in 10 out of 13 pigs killed between 10 and 18 days after inoculation a non-suppurative encephalomyelitis was detected histologically. No lesions were detected in 4 pigs killed 4 days after inoculation, and only slight lesions were detected in 1 of 2 pigs killed 22 days after inoculation. There was no evidence that F7 virus was pathogenic for mice or chicken embryos. F7 virus was serologically distinct from the Talfan and Konratice strains of Teschen virus; the S180/4 and T52A strains of porcine encephalomyelitis virus; the PE-1 porcine enterovirus and from a number of human enteroviruses. The use of sera of high titre suggested a minor antigenic relationship between F7 and the T80 porcine enterovirus.

The growth in vitro of vaccinia virus in chick embryo chorio-allantoic membrane, minced embryo and cell suspensions.

The growth curve of rabbit skin-adapted vaccinia virus in the chick chorioallantoic membrane incubated in Hanks' solution showed a drop in titre of virus for about 10 hr. followed by growth. At least 25% of virus, sometimes more, remained infective. A similar fall in titre was observed in heated membranes in which the virus did not grow and this occurred also when membranes, either normal or heated, were infected and disintegrated before incubation.The growth curve of virus in minced chick-embryo was similar to that in chorioallantoic membrane.Virus in cell suspensions prepared from chick embryo and incubated in a nutrient medium showed only a small loss of infectivity before growth in some experiments and rarely dropped below 65–70 % of the original titre in others.These results throw considerable doubt on the view that loss of infectivity preceding growth of vaccinia virus should be interpreted as an essential part of a growth cycle.

ANTIBODY RESPONSES TO NATURALLY OCCURRING POLIOMYELITIS INFECTIONS IN CHILDREN

Serums collected over an 18-month period from children with a clinical diagnosis of poliomyelitis were studied by means of the complement fixation test. Test antigens were prepared from the nutrient fluid of tissue cultures infected with each of the 3 known types of poliomyelitis viruses. Results were compared with those obtained from neutralization tests on the same serums. The complement fixation test was of little diagnostic help in these patients; a high titer, a rise in titer, and a fall in titer were all inconstant findings. A complement fixing antibody titer persisting beyond 100 days was more indicative of the immunologic type of the infecting virus than any other feature of the complement fixing antibody response. The multitypic nature of the complement fixing antibody response was discussed in relation to the complex antigenic structure of poliomyelitis viruses.

THE EFFECTS ON BIOLOGICAL MATERIALS OF FREEZING AND DRYING BY VACUUM SUBLIMATION

The infectivity titre of influenza virus-infected allantoic fluid was determined after a variety of procedures involving cyclic slow freezing and thawing, freezing at various rates with subsequent storage at different temperatures freezing at various rates with subsequent dehydration at various temperatures, and different degrees of dehydration. All these factors were found to influence the survival rate of the virus particles. Five freeze-thaw cycles resulted in a fall in titre from 10(-8.6) to 10(-0.8) cycles 2, 3, and 4 causing much greater losses than cycles 1 and 5. Rapid cooling to -40 degrees C. or slow cooling to -80 or 190 degrees C. did not cause significant titre loss, but rapid cooling to temperatures above -40 degrees or slow cooling to temperatures above -80 degrees C. caused definite titre loss. Loss of titre on storage occurred only at temperatures above -40deg;C. The effect of lyophilization depends both on the preliminary treatment and on the dehydration temperature. Better conservation of titre was obtained after preliminary cooling to -190 or -80 degrees C. than after preliminary cooling to higher temperatures. The most effective sublimation temperatures were 0 and -80 degrees .; the least effective was +20 degrees C. Titre losses in suspensions sublimated at -10, -30, and -60 degrees C. were in general intermediate. No loss in titre occurred after preliminary cooling to -80 or -190 degrees C. and subsequent dehydration at -80 or 0 degrees C. The degree of dehydration definitely affects the survival of virus on storage at 0 degrees C., but sublimation for 4 hours at 0 degrees C. gave complete protection against titre loss on storage at this temperature. Possible explanations of the observations made are suggested, based on known physiochemical phenomena such as supercooling, vitrification, variations in size and shape of ice crystals with different freezing speeds, differential enzyme inactivation, changes in salt concentration, and changes in energy levels.

Attempt to prevent erythroblastosis foetalis by use of cortisone during pregnancy.

Since the discovery by Landsteiner and Wiener (1940) of the rhesus factor great advances have been made in the understanding of erythroblastosis foetalis, and it is now firmly established that the condition results from the development in the pregnant woman of immune antibodies capable of crossing fhe placental barrier and causing excessive red-cell destruction in the foetus. This recent knowledge has led to several attempts to inhibit the development of such antibodies. Thus Wiener and Sonn (1946) gave injections of typhoid and pertussis vaccines during pregnancy in the hope that the administration of a strong antigen might interfere with the development of antibodies in response to the weaker (Rh) antigen. Kariher (1947), acting upon reports that ethylene disulphonate was alleged to be of value in allergic conditions, administered this substance in minute amounts to pregnant women who had pre viously given birth to infants with haemolytic disease. His results suggested that such treatment may have some effect in lowering the antibody titre in the maternal serum. Carter (1947, 1949) claimed to have isolated from human Rh-positive red cells a fraction containing an Rh hapten, and reported that injections of this frac tion into Rh-sensitized pregnant women resulted in a fall in titre of the circulating Rh antibodies. Other workers, notably Howe and Rustigian (1950), and Spurling et al. (1950), have failed to produce results comparable to those of Carter. So far no widely accepted therapeutic procedure has resulted from these attempts to inhibit Rh antibodies. At the present time the effects of cortisone and A.C.T.H. upon immunity reactions are incompletely understood. The available reports indicate a species difference: cf. guinea-pig (Dews and Code, 1951), rabbit (Germuth and Ottinger, 1950), and man (Mirick, 1951). In man A.C.T.H. and cortisone apparently do not inhibit the development of antibodies (Havens et al., 1951) but are able to prevent hypersensitivity reactions (Long and Favour, 1950). It seems that in man the adrenal agents prevent either the union of antigen and antibody or the tissue injury which results from such union.

Experimental hypersensitivity in the rabbit; effect of inhibition of antibody formation by X-radiation and nitrogen mustards on the histologic and serologic sequences, and on the behavior of serum complement, following single large injections of foreign Proteins.

X-radiation and nitrogen mustard administration inhibit the formation of precipitins for whole bovine serum and bovine serum gamma globulin in the rabbit. When specific antibody formation is inhibited by these agents, intravenous injection of a single large dose of bovine serum gamma globulin is not usually followed by the development of tissue lesions 9 to 11 days later, as occurs fairly regularly in control animals. A fall in titre of serum complement to very low levels for 3 to 5 days is closely correlated in time with the disappearance of antigen from the circulation following the intravenous injection of single large doses of bovine serum albumin and bovine serum gamma globulin. A rise in complement titre to normal levels occurs as antibodies appear in the serum. This sudden fall in complement titre is correlated with the development of characteristic lesions, and does not occur when antibody formation is inhibited. The data presented are interpreted as evidence in favor of the concept that the lesions are due to a reaction between antigen fixed in or on tissue cells and circulating antibody. The possible significance of serum complement in the pathogenesis of anaphylactic tissue lesions is discussed.

POLIOMYELITIS IN FAMILIES ATTACKED BY THE DISEASE

A study has been made concerning the presence, and persistence of neutralizing antibodies to poliomyelitis virus in six individuals. Five individuals had poliomyelitis; the remaining subject was a familial contact. Neutralizing antibodies do appear in the serums of patients convalescent from poliomyelitis. In this study neutralizing antibodies, as a rule, appeared during the first ten days of illness. There is the suggestion that these antibodies appear rapidly, quickly reach their highest level, and that there is little if any fall in titer during the ensuing year. The neutralizing antibody titer may not reach a high level in a considerable number of patients.

Results of Heterophile Antibody Agglutination and Kahn Tests in Patients with Viral Hepatitis.

SummaryHeterophile antibody agglutination, Kahn, and cold agglutinin tests were performed in 2 groups of patients with viral hepatitis. Sixteen out of 508 patients (3%) developed positive heterophile antibody tests with titers of 1:56 which were reduced to 1:7 or negative by absorption on boiled guinea pig kidney. A rise and/or fall in titer of antibody was demonstrable in serial weekly determinations. Out of 388 patients who were known not to have syphilis, 6 (1.5%) developed positive Kahn tests, and 10 others (2.5%) had doubtful tests. Two out of 323 patients had cold agglutinins present in a titer of 1:32.The relatively small number of positive heterophile antibody agglutination and Kahn tests is in contrast to reports of others25 who have found a considerably higher percentage of positive tests.

THE COMPLEMENT FIXATION REACTION IN MONKEY MALARIA

1. A specific complement fixation reaction test for Plasmodium knowlesi malaria in rhesus monkeys is reported with details involved in the preparation of the antigen and procedures employed in setting up the test. 2. It was found that specific complement-fixing antibodies appeared early in the course of the experimental disease and persisted during the course of the chronic infection. 3. The first appearance of complement-fixing antibodies was generally followed by a temporary fall in titer. During the first 2 months of infection there was no apparent relationship between the number of circulating parasites and the changes in complement fixation titer. 4. During the stage of chronic infection there was a fall in the titer of complement-fixing antibodies preceding each parasitic relapse, and after the relapse had terminated, there was an elevation of the complement-fixing titer.

Antistreptolysin Titers in Rheumatoid Arthritis

The findings of Todd, Coburn and Pauli, and others indicate that the antistreptolysin test furnishes an accurate method for determining the presence of recent infection with hemolytic streptococci of group A. Coburn and Pauli showed that, following hemolytic streptococcal infections, the antistreptolysin titer of the serum rises rapidly, remains elevated for a variable number of months and gradually tends to return to normal values. In nearly all cases in their series there was an appreciable fall in titer within 6 months and within 2 years over half the cases had reached natural levels. Myers and Keefer studied the antistreptolysin titer in 13 cases of active rheumatoid arthritis and found that, although the titers varied considerably, the average was not greater than in normal individuals. They stated that “in most of these patients the disease had existed for many months.” Blair and Hallman determined the antistreptolysin titer in 45 patients with rheumatoid arthritis and found it to be above the normal range (over 100 units per cc.) in one-third of the cases. In their report no reference was made to the duration of the disease at the time of the observations or to the nature of the onset. We have determined the antistreptolysin titer in 219 cases of rheumatoid arthritis, including 22 cases of rheumatoid spondylitis (Marie-Strümpell). Preliminary observations, indicated that in the great majority of well established cases the titer was within normal limits, irrespective of the degree of clinical activity present. However, when the sera of early cases with acute onset were examined quite different results were obtained. In the present report, therefore, the cases are divided into 2 groups, “early” and “late” cases. For convenience, cases of less than one year's duration are considered as “early” and those of longer duration are considered as “late”. In addition, the nature of onset, whether acute, subacute or insidious, has been recorded in each instance.