bluuebunny/crossref_metadata_2025 huggingface dataset:
DEMONSTRATION OF AN EPITHELIAL ANTIGEN IN COLON BY MEANS OF FLUORESCENT ANTIBODIES FROM CHILDREN WITH ULCERATIVE COLITIS
Authors: Broberger Ove , Perlmann Peter
Published: June 2004

Thirteen sera from children with ulcerative colitis were examined for antibodies reacting with constituents of human colonic tissue by means of immunofluorescent methods. 3 out of 10 sera reacted positively when tested by the direct staining method while 6 out of 13 reacted positively when tested by the indirect method with conjugates of rabbit anti-human gamma globulin. The specificity of the reactions could be confirmed by inhibition tests. 16 sera from healthy children and adults yielded completely negative results. The staining capacity of various sera was correlated to their hemagglutinating titer when they were tested with sheep erythrocytes, coated with phenol-water extract of human colon. Absorption experiments indicated that the stainable antigen was also present in the extracts used for the hemagglutination experiments.

In unfixed tissue sections, fluorescent antibodies were adsorbed onto the epithelial cells of the mucosa. Adsorption on epithelial basement membranes could not be demonstrated. Fluorescent H agglutinins, isolated from eel serum, were adsorbed onto the same mucosal structures of human colon (blood group O) as the antibodies in the sera of patients with ulcerative colitis. However, any immunological relationship between H substance and the colonic antigen of ulcerative colitis could be ruled out by cross-inhibition and hemagglutination inhibition experiments.

Fluorescent serum from patients with rheumatoid arthritis also stained sections of human colon but the localization of the stainable antigens was different from that visualized with the ulcerative colitis sera. Inhibition experiments indicated that the rheumatoid arthritis serum contained antibodies staining colon antigens different from those reacting with antibodies in the ulcerative colitis sera. Sera from patients with systemic lupus erythematosus or with the nephrotic syndrome, which all hemagglutinated erythrocytes coated with colon extract, did not stain the sections of the colon tissue either because of suboptimal antibody concentration or because of a difference in type or localization of the antigen.
STUDIES ON NATURAL ANTIBODIES TO GRAM-NEGATIVE BACTERIA
Authors: Michael J. Gabriel , Whitby James L. , Landy Maurice
Published: June 2004

A study was made of the origin, occurrence, and properties of natural antibodies to Gram-negative bacteria in the normal serum of several species. Antibody was measured by a procedure based on the bactericidal reaction carried out under conditions in which activity was a function of the amount of antibody contributed by the test serum.

Antibody to seven genera of the family Enterobacteriaceae were demonstrated in normal human serum. The specificity of these antibodies was affirmed by absorption with homologous bacteria and by inhibition of bactericidal activity with purified homologous somatic antigen. Absorption with graded amounts of bacterial suspensions showed that a large excess of bacteria led to non-specific removal of antibodies. Analogous findings were also made with immune antibody.

As determined by quantitative absorption tests no difference could be found in the avidity of natural and immune antibody. Natural antibody in the serum of various species differed considerably as regards their lability to heat, but in parallel tests immune antibody of each species was significantly more heat-stable.

The time and appearance of the antibodies varied in young animals, of different species. Mice developed these antibodies at the earliest age, with guinea pigs, rats, and rabbits following in that order.

Serum from germ-free rats and chickens had no demonstrable antibodies to E. coli or S. typhosa whereas these antibodies were present in the serum of litter mates reared under conventional conditions. On the other hand germ-free and conventional mice did not differ appreciably as regards the levels of these same antibodies.
AUTORADIOGRAPHIC STUDIES ON THE IMMUNE RESPONSE
Authors: Mäkelä O. , Nossal G. J. V.
Published: June 2004

The DNA-synthesizing capacity of single antibody-forming cells was tested by a combination of micromanipulatory and autoradiographic techniques. Rats were immunized with S. adelaide flagellin, a protein antigen known to contain significant contamination with somatic (O) antigen. Single cells from secondarily immunized rats were tested for production of anti-H and anti-O antibodies by previously described and newer techniques. Positive antibody producers were transferred onto clean dry slides by micromanipulation, and autoradiographs were performed. When rats had received tritiated thymidine 1 hour before killing, labeling of antibody-forming cells was taken to imply that the cell was preparing for further mitotic division. It was found that on the 2nd and 3rd day of a secondary response, many of the antibody-producing cells in the nodes (chiefly plasmablasts) were incorporating tritiated thymidine. At the height of the cellular response, however, at 4 and 5 days, the majority of active antibody producers (chiefly mature plasma cells) were incapable of DNA synthesis. There appeared to be an inverse relationship between the antibody-forming and DNA-synthesizing capacities of the cell population under study; as more of the cells studied formed detectable antibody, fewer of them incorporated the DNA precursor.

The age of plasma cells was also studied. Animals were killed at the height of the cellular immune response, having previously received an injection of tritiated thymidine 1 to 48 hours before killing; i.e., at 63 to 110 hours after their secondary stimulus. As the interval between isotope injection and killing increased, the proportion of antibody-forming cells showing labeling increased. With an interval of 30 hours, about half the antibody-forming cells were labeled and of 48 hours, over 95 per cent were labeled. This was taken as evidence that, few, if any, antibody-forming cells found at the height of a secondary response were more than 48 hours old.

On the basis of these experiments and those reported in the accompanying paper, a simplified scheme showing the development of an antibody-forming clone in the secondary response was proposed.
IMMUNE CYTOLYSIS: ELECTRON MICROSCOPIC LOCALIZATION OF CELLULAR ANTIGENS WITH FERRITIN-ANTIBODY CONJUGATES
Authors: Easton John M. , Goldberg Burton , Green Howard
Published: June 2004

Immune gamma globulin has been coupled to ferritin by the diisocyanate method of Singer. The final product ("ferroglobulin") had approximately 13 per cent of its gamma globulin coupled to ferritin, and roughly half of its ferritin coupled to gamma globulin. The uncoupled gamma globulin could be removed by ultracentrifugal sedimentation of the free ferritin and the ferritin-antibody conjugates. The characteristics of the native antibody were retained by the ferritin-antibody conjugates, for they could be precipitated by anti-gamma globulin antisera, and when used as antibodies, they reacted specifically with soluble and cellular antigens.

Ferroglobulin preparations made from rabbit antisera against whole ascites tumor cells were incubated with the cells, and the location of ferritin determined by electron microscopy of thin-sectioned material. It was found that the immune ferroglobulins localized specifically on antigens of the cell membrane. Some of the ferritin label entered the cells by pinocytosis, but the ferritin-antibody units did not appear able to pass directly through the cell membrane into the cytoplasmic matrix.

When cells were incubated with ferritin-labeled antibody and complement, antibody could be located in the cytoplasmic matrix, and it therefore appeared that complement action was required before antibody could pass directly through the cell membrane. This finding was consistent with previous observations that the plasma membrane of an antibody-complement treated cell becomes permeable to large molecules.

In broken cell preparations incubated with ferroglobulin, antibody combined with amorphous material and with structures derived from cell membranes and from smooth membranes of the endoplasmic reticulum. The data favor the concept that antigens contained within the membranous structures are most important in the formation of cytotoxic antibodies.

The reported experiments support the view that cytotoxic antibodies fix primarily to surface antigens of the cell membrane. The subsequent action of complement establishes the permeability defect that induces the osmotic lysis of the cell and permits antibody to pass into the cell where it may act in a similar fashion on intracellular organelles.
THE LOCALIZATION OF IN VIVO BOUND COMPLEMENT IN TISSUE SECTIONS
Authors: Lachmann P. J. , Müller-Eberhard H. J. , Kunkel H. G. , Paronetto F.
Published: June 2004

A technique has been described for the demonstration of a human complement component by an immunofluorescent method. The component detected is ß1C-globulin, a moiety of the third complement component, which has previously been obtained in pure form and to which a specific antiserum has been prepared.

It has been shown in a model system that the binding of ß1C-globulin as shown by immunofluorescence is strictly equivalent to complement fixation as assessed by standard serological methods.

This technique has been applied to the detection of in vivo bound complement in pathological human tissues. It was found that in vivo complement binding occurs in the lesions of several human diseases, but not elsewhere in the same tissues. In a rather limited survey of diseases that has been carried out, in vivo complement binding was found particularly in systemic L.E., various nephritides, and amyloidosis, as well as in single cases of some other diseases.

The spectrum of in vivo complement binding has been compared with that of γ-globulin binding (7S and 19S types) and with the demonstration of in vitro complement fixation and rheumatoid factor fixation. It was distinct from each of these. Rheumatoid factor fixation, detected by anti-19S antiserum showed promise as a method for the detection of antigen-antibody complexes and aggregated γ-globulin in tissue sections.

The interpretation of these findings in regard to the nature of the binding sites, and their possible significance in regard to pathogenic mechanisms have been discussed.
IMMUNOHISTOCHEMICAL LOCALIZATION OF HUMAN CHORIONIC GONADOTROPIN
Authors: Midgley A. R. , Pierce G. B.
Published: June 2004

Through the use of immunohistochemical techniques, human chorionic gonadotropin has been localized to syncytiotrophoblastic cells of immature placenta, hydatidiform mole, chorioadenoma destruens, and choriocarcinoma. No gonadotropin has been detected in cytotrophoblast. Evidence is discussed which suggests that syncytiotrophoblast is the cell of origin of human chorionic gonadotropin.

The observation that formalin fixation did not alter the ability of human chorionic gonadotropin to react with its specific antibody permitted the study of formalin-fixed paraffin-embedded tissues stored in the tissue collection. In addition, the excellence of histologic preparations following formalin fixation facilitated cytologic identification.
PROPERTIES OF ACATALASIC CELLS GROWING IN VITRO
Authors: Krooth Robert S. , Howell R. Rodney , Hamilton Howard B.
Published: June 2004

Acatalasia, a disease due to homozygosity for a Mendelian gene, is characterized by the absence of the enzyme catalase from the tissues of the human body. Red cells from heterozygotes have enzyme activities about one-half normal. In this paper, the development of cell lines from skin biopsies on an affected homozygote, a heterozygote, and eight control patients is described. The cell type is the euploid "fibroblast."

It was found that acatalasic cells lacked the enzyme, even after growing for many months in a medium rich in catalase. The control lines all had mean catalase activities double or more that of the heterozygous line. Selection experiments, in which the growth of cells exposed for 20 minutes to varying concentrations of hydrogen peroxide was measured, did not provide a system for preferentially eliminating acatalasic cells.

Certain other experiments bearing on the enzymatic defect in this disease were performed.
PLASMA CELL NEOPLASIA IN A SINGLE HOST: A MOSAIC OF DIFFERENT PROTEIN-PRODUCING CELL TYPES
Authors: Potter Michael
Published: June 2004

The peritoneal plasma cell neoplasias that develop in strain BALB/c mice after the injection of adjuvant-staphylococcus mixtures or mineral oil alone appear in the form of multiple nodules in the mesentery and on peritoneal surfaces. Experiments were done to determine if these nodules were metastases or multiple primary neoplasms. Nodules or pieces of masses were transplanted subcutaneously by the trochar method or by insertion of tissue under the kidney capsule from 6 primary cases and parallel transplant lines were established. The serum and urinary protein abnormality (a stable heritable characteristic) of each of the various transplant lines was characterized by agar gel electrophoresis and immunoelectrophoresis. Different protein-producing lines were found in 3 cases; in one case 5 different protein-producing lines were isolated. Two different lines were found for each of the other 2 cases. When transplantation studies were begun early, it was demonstrated that the nodules were multiple primary plasma cell neoplasms; when delayed, only one protein-producing plasma cell neoplasm was found.
THE ROLE OF IMMUNITY IN THE PATHOGENESIS OF EXPERIMENTAL HEMATOGENOUS PYELONEPHRITIS
Authors: Sanford Jay P. , Hunter Betty W. , Souda Lona L.
Published: June 2004

Hematogenous pyelonephritis was produced in rats utilizing multiple strains of Escherichia coli, a strain of Klebsiella pneumoniae, and a strain of Proteus mirabilis.

Three patterns of hematogenous pyelonephritis occurred which represent an interrelationship between an immune response to the infecting bacteria and the development of obstructive uropathy as a consequence of infection. First, the course of pyelonephritis due to strains of Escherichia coli was acute, self-limited, and associated with the development of circulating agglutinins. Following healing, this pattern of infection was associated with acquired resistance to reinfection with the same bacterial strain. Second, the course of pyelonephritis due to a strain of Klebsiella pneumoniae type C was chronic. This infection was not associated with the production of circulating agglutinins against encapsulated strains. Acquired resistance to reinfection by the homotypic strain could not be demonstrated following eradication of infection but was produced by the passive transfer of concentrated antiserum. Third, pyelonephritis due to Proteus mirabilis was associated with circulating agglutinins and resistance to reinfection with the same organism following eradication of infection, yet the course was chronic. The chronicity appeared to be the consequence of obstructive uropathy resulting from calculi which developed during the course of the infection.

Resistance to reinfection was demonstrated in infections with strains of E. coli and P. mirabilis. The resistance is associated with specific immunity as demonstrated by the observation that: (a) it is type-specific, (b) it is of at least 3 months' duration, and (c) it can be passively transferred by means of rabbit antiserum. Since K. pneumoniae failed to evoke capsular antibodies in the rat, resistance to infection with K. pneumoniae was produced only by means of passively transferred concentrated rabbit antiserum and not by prior infection.

Immunity can be demonstrated to have a significant role in the pathogenesis of experimental hematogenous pyelonephritis only in the absence of obstructive uropathy.
CYTOCHEMICAL AND ELECTRON MICROSCOPIC STUDIES OF RAT LIVER WITH REDUCED CAPACITY TO TRANSPORT CONJUGATED BILIRUBIN
Authors: Goldfischer Sidney , Arias Irwin M. , Essner Edward , Novikoff Alex B.
Published: June 2004

Although the livers of rats treated with agents known to suppress bilirubin transport appeared relatively normal on routine histological sections, cytochemical and electron microscopic preparations revealed marked changes in: (a) levels of alkaline phosphatase and apparent ATPase activities of the cell membrane at the sinusoids, bile canaliculi, and between adjacent cells; (b) morphology of the bile canaliculi such as dilatation, fragmentation, vesiculation and reduced numbers of microvilli; (c) the number of lysosomes and their distribution within the cell. Similar changes in the cytochemistry of the liver cell were induced by extrahepatic obstruction.
ESCHERICHIA COLI ASSOCIATED WITH COLOSTRUM-FREE NEONATAL PIGS RAISED IN ISOLATION
Authors: Lecce James G. , Reep Bryan R.
Published: June 2004

Escherichia coli 08 was the most frequent coliform isolated from the blood and liver of morbid and dead neonatal, colostrum-free piglets raised under extremely sanitary conditions. This strain accounted for 67 per cent of the typable E. coli. The next most numerous strain occurred at a frequency of 6 per cent. Hence, E. coli 08 was considered the main coli enteropathogen in our experimental, isolated environment.

In random samples of the feces of healthy and diarrhetic neonatal piglets, 24 per cent of the typable E. coli was type 08. When a directed effort was made to isolate E. coli 08 from the feces of neonatal piglets in a healthy, colostrum-free litter, this strain was isolated from 17 per cent of the total E. coli colonies examined. Thus, the enteropathogen E. coli 08 was ubiquitous in the feces of piglets in our environment, making up approximately 20 per cent of the fecal E. coli.

85 per cent of the bacteremia and death in which E. coli was isolated from blood or liver occurred in piglets fed diets void in bovine and porcine gamma globulin.

Tube agglutination tests demonstrated that agglutinins to E. coli 08, and other serotypes as well, were present in bovine colostrum and to a lesser extent in porcine colostrum. These agglutinins were practically lacking in solutions of porcine and bovine gamma globulin.

Feeding 109 E. coli 08 bacteria to 2-week-old, colostrum-free, gamma globulin-free, 08 agglutinin-free piglets did not produce visible disease.
THE ROLE OF INTERFERON IN VACCINIA VIRUS INFECTION OF MOUSE EMBRYO TISSUE CULTURE
Authors: Glasgow Lowell A. , Habel Karl
Published: June 2004

The production of an interferon-like substance by vaccinia virus is described. The physical properties of vaccinia interferon are shown to be similar to those of previously reported interferons.

Data defining the role of vaccinia interferon in cell resistance and in establishment and maintenance of a carrier culture are presented.

Elimination of virus from an infected culture is demonstrated and the role of interferon in the recovery process is considered.
AN IMMUNOLOGIC STUDY OF TWO METABOLICALLY ACTIVE PEPTIDES FROM THE ANTERIOR PITUITARY GLAND
Authors: Friesen Henry , Irie Minoru , Barrett Richard J.
Published: June 2004

Peptides I and II, two metabolically active peptides from porcine pituitary glands, stimulated antibody production in rabbits. The antiserum obtained had antibodies which interacted with peptides I and II from porcine pituitaries, peptides I and II from human pituitaries, and fraction H prepared by Rudman from hog pituitaries. None of the other pituitary preparations tested showed any interaction with peptides I and II.

All three preparations stimulated the release of free fatty acids from rabbit adipose tissue in vitro. Antiserum inhibited this biological action to a different extent in each of the three preparations. Following an intravenous injection of peptides I and II there was a rapid rise in the plasma concentration of free fatty acids in rabbits. Injection of antiserum together with peptides I and II failed to block the rapid increase in free fatty acids. However, an injection of at least ten times the minimal amount of peptides I and II which raised the plasma free fatty acid concentration produced no increase in a rabbit with a high antibody titer to these peptides.
QUANTITATIVE STUDIES OF THE SENSITIVITY OF NORMAL AND NEOPLASTIC MOUSE CELLS TO THE CYTOTOXIC ACTION OF ISOANTIBODIES
Authors: Möller Erna , Möller Göran
Published: June 2004

Experiments were performed to study the mechanisms of the sensitivity of normal and neoplastic mouse cells to the cytotoxic action of humoral isoantibodies.

A quantitative in vitro absorption procedure was used to compare the residua] hemagglutinin titer of a certain isoantiserum after the absorption of a known volume with known cell numbers. The cell numbers were adjusted so as to yield the same average total cell surface area. Lymph node cells and various solid and ascites tumor cells of strain A and C3H origin were used. It was found that different cell types differed with regard to their concentration of isoantigenic surface receptors. High correlation coefficients were found between the cytotoxic sensitivity and the concentration of isoantigenic receptors.

It was shown that tumor cells which were partially or completely resistant to a single isoantiserum could be made sensitive to humoral isoantibodies provided that they were treated with mixtures of antisera, produced in different donor genotypes against the same target genotype, since each individual genotype reacts against a different antigen combination. This supports the concept that cytotoxic sensitivity is related to the surface concentration of reactive sites.

Hematopoietic liver cells of newborn mice, which are completely resistant to isoantibodies, and spleen and lymph node cells of adult animals which are highly sensitive, were compared with regard to their ability to take up fluorescein-conjugated normal mouse serum in vitro. No differences were found between their visible pinocytotic uptake. Similar experiments were performed with various ascites tumor cells having different cytotoxic sensitivity. All tumor cells studied had a low pinocytosing ability which was not correlated to their sensitivity to humoral isoantibodies.
ON THE RELATION OF NECROSIS AND INFLAMMATION TO DENATURATION OF PROTEINS
Authors: Opie Eugene L.
Published: June 2004

Necrosis of the skin was produced by the injection of measured quantities of electrolytes and of amino compounds into the dermis, and the relative ability of these substances to produce it was determined. Inflammation characterized by edema and accumulation of leucocytes accompanied necrosis.

The ability of electrolytes to produce necrosis was found to increase with the valence of their basic ion, and in this respect was in accord with their ability to denature proteins.

The quantity of different electrolytes needed to produce necrosis varied in the same order as the molar concentration of these electrolytes, that is isotonic with liver or kidney cells. Necrosis caused by amino compounds occurred with similar relation to the isotonicity of liver cells. In this as in other relations the cells acted as osmometers.

The foregoing relations indicate that denaturation of proteins, necrosis of living tissue, and osmotic activity of liver or kidney cells are determined by molecular weight, valence, and ion-dissociation of electrolytes, that is, by the factors that determine the colligative properties of electrolytes.

Agents such as turpentine, mustard, or croton oil and some halogen substitution compounds of methyl that are insoluble in water and soluble in lipoids have produced skin necrosis and inflammation.
POLYFUNCTIONAL DINITROPHENYL HAPTENS AS REAGENTS FOR ELICITATION OF IMMEDIATE TYPE ALLERGIC SKIN RESPONSES
Authors: Parker Charles W. , Kern Milton , Eisen Herman N.
Published: June 2004

Dinitrophenyl derivatives of differing molecular weights and degrees of substitution have been contrasted with respect to their ability to elicit immediate type allergic responses and their capacity to induce antibody formation in the guinea pig. In contradistinction to dinitrophenyl-proteins, bis-DNP-lysine and DNP-polylysines (including a 100,000 molecular weight derivative) failed to induce antibody detectable by guinea pig passive cutaneous anaphylaxis. Dinitrophenyl-polylysines evoked urticarial responses non-specifically, but after succinylation were about as effective as dinitrophenyl-proteins in eliciting specific cutaneous reactions. An important factor influencing the effectiveness of bis-DNP-lysine in evoking specific wheal-and-erythema responses is antibody affinity for the dinitrophenyl-lysyl determinant.
HYPERSENSITIVITY TO PENICILLENIC ACID DERIVATIVES IN HUMAN BEINGS WITH PENICILLIN ALLERGY
Authors: Parker Charles W. , Shapiro Jack , Kern Milton , Eisen Herman N.
Published: June 2004

Multifunctional derivatives of penicillenic acid are effective elicitors of wheal-and-erythema skin responses in humans allergic to penicillin. Of the effective derivatives, penicilloyl-polylysines are particularly attractive as skin test reagents because they appear to be incapable of inducing antibody formation. The skin responses are specifically inhibitable in most instances by homologous unifunctional haptens. The penicillenic acid derivatives which appear to be determinants of human allergic reactions to penicillin are: penicilloyl, penicillenate, and groups of the penamaldate-penilloaldehyde type. Of these, the most significant appears to be the penicilloyl-lysyl determinant.
SARCOMAS IN HAMSTERS AFTER INJECTION WITH ROUS CHICKEN TUMOR MATERIAL
Authors: Ahlström C. G. , Forsby Nils
Published: June 2004

Newborn hamsters were injected subcutaneously with a suspension of finely minced Rous chicken sarcoma (Schmidt-Ruppin strain). After an interval of about 2 weeks, progressively growing sarcomas developed at the site of injection in almost all animals. Also in adult hamsters inoculated intramuscularly with the same material sarcomas developed at the site of injection within 2 to 4 months. Secondary growths appeared on the peritoneal surface, in the retroperitoneal and mediastinal lymph nodes and in the lungs. The sarcomas usually had a pleomorphic appearance and showed a certain resemblance to rhabdomyosarcoma, but sometimes they had the character of spindle cell sarcomas of varying degree of maturity. Sarcomas were not only obtained in hamsters injected with cellular material from the Rous chicken sarcoma but were also seen in hamsters which were injected at birth or when 2 months' old with supernatant fluid obtained by repeated centrifugation of suspensions of homogenized chicken sarcoma, and presumed to be cell-free.

The hamster sarcoma was transplanted to a newborn hamster and could then without difficulties be passed in series in hamsters. All attempts to transfer the sarcoma from hamster to hamster by means of cell-free material from the hamster sarcoma failed. On the other hand, material from the hamster sarcomas inoculated into chickens induced rapidly growing Rous sarcomas at the site of inoculation. This proved possible not only with material from the first but also from later passages of the tumor in hamsters.

It is concluded that the strain of Rous virus used has the capacity to induce sarcomas not only in chickens but also in hamsters.
RETICULOENDOTHELIAL CLEARANCE OF CIRCULATING FIBRIN IN THE PATHOGENESIS OF THE GENERALIZED SHWARTZMAN REACTION
Authors: Lee Leung
Published: June 2004

Intravenous injections of endotoxin or infusions of thrombin in the rabbit initiate intravascular coagulation but do not usually result in massive deposition of fibrin. It has been proposed that the reticuloendothelial system may function efficiently in the removal of circulating fibrin; its blockade permits reproduction of all of the features of the generalized Shwartzman reaction by infusions of thrombin. In the rabbit the reticuloendothelial system may constitute the major protective mechanism against the vasculo-occlusive lesions of the generalized Shwartzman reaction, which appears to be the direct consequence of intravascular fibrin formation and deposition.
PASSIVE TRANSFER OF TRANSPLANTATION IMMUNITY
Authors: Najarian John S. , Feldman Joseph D.
Published: June 2004

Passive transfer of tritiated thymidine labeled lymphoid cells sensitized to homologous tissues into non-sensitized isologous hosts resulted in accelerated rejection of homologous skin grafts in the recipients. Despite 33 per cent label of the suspension, only rare labeled sensitized lymphoid cells could be found at the site of rejection.

Passive transfer of sensitized lymphoid cells in millipore chambers implanted subcutaneously or intraperitoneally in non-sensitized isologous hosts resulted in accelerated homograft rejection in the recipients. Transfer of transplantation immunity could not be accomplished with serum from sensitized hosts.

The rejection of homologous tissues without the physical presence of the sensitized cell at the graft site suggested that a humoral agent produced by the cell was capable of rejecting the homograft.
A STUDY OF THE MECHANISMS OF DNA AND THYMINE DEGRADATION IN CULTURED HUMAN CELLS INFECTED WITH A LIPOVIRUS
Authors: Chang R. Shihman , Liepins H.
Published: June 2004

DNA and thymine degradation on cultured human, mouse, and chick cells were studied. Significant increase in DNA-degrading activity was demonstrated in human embryonic cells killed by freeze-thawing, liver cells killed with mitomycin C, mouse embryonic cells infected with encephalomyocarditis virus, and in all cells killed by the lipovirus. Twelve other viral agents, actinomycin D, and 5-fluorodeoxyuridine failed to produce a similar increase.

Thymidine-2-C14-labeled cultures, either live, killed, or infected by 19 different physical-chemical and biological agents, did not release detectable quantity of C14C2. Following infection with the lipovirus 20 to 60 per cent of the total radioactivity of thymidine-2-C14-labeled cultures was liberated as C14O2. It was postulated that the lipovirus introduced into the host cells the missing genetic information necessary for the synthesis of one or more enzymes responsible for the reductive catabolism of thymine.
THE CHARACTERIZATION OF STAPHYLOCOCCAL TOXINS
Authors: Kumar Surendra , Lindorfer Robert K.
Published: June 2004

The continuous flow paper electrophoretic methods used to isolate alpha hemolysin are presented.

The purity of the alpha hemolysin preparation is demonstrated by double agar diffusion, immunoelectrophoretic, and ultracentrifugation techniques.

Indirect evidence of purity is provided by the fact that rabbits immunized with purified alpha hemolysin produced detectable antibody only to alpha hemolysin.

Direct support is given to the "unitarian theory" by the demonstration that purified alpha hemolysin also possessed dermonecrotic, lethal, and leucocidal activities.

Further studies dependent on the availability of purified alpha hemolysin are outlined.
STUDIES OF THE GENERALIZED SHWARTZMAN REACTION PRODUCED BY DIET
Authors: Kaunitz Hans , Malins Donald C. , McKay Donald G.
Published: June 2004

By molecular distillation of oxidized cod liver oil a partial isolation of the lipid species responsible for the diet-induced generalized Shwartzman reaction in pregnant rats has been achieved.

Molecular distillation produced three fractions and a residue. Qualitative and quantitative differences in each fraction were shown by determining iodine and saponification numbers and by thin layer chromatography on silicic acid.

The incidence of the Shwartzman reaction was higher with fraction III than with either of the other two fractions, the residue, or the original oxidized cod liver oil. It is evident that the toxic factor or factors can be concentrated by molecular distillation.

The high temperatures used in the molecular distillation destroy peroxides in the lipids. Therefore, in spite of the fact that oxidation of dietary fats is necessary to produce the reaction, peroxides in the dietary lipid are not necessary for the development of the tissue reaction.

The residue fraction contains high molecular weight polymers and the incidence of the Shwartzman reaction is low in animals fed this material. It is unlikely that high molecular weight polymers are responsible for the tissue reaction.

Animals that do not gain weight at a rate close to that of the normal pregnant rat do not develop the reaction.

Conversion of fraction III into its ethyl esters increased the incidence of the Shwartzman reaction in two experiments. Esterification appears to "unmask" a certain amount of the active factor.

The specific lipid material or materials responsible for the development of the generalized Shwartzman reaction remains to be found.
STUDIES OF THE GENERALIZED SHWARTZMAN REACTION PRODUCED BY DIET
Authors: McKay Donald G. , Wong Ting-Chao
Published: June 2004

A 4-fold reduction in the death rate of pregnant rats subjected to a diet capable of inducing the generalized Shwartzman reaction was obtained by the administration of oral absorbable and non-absorbable antibiotics. The possible mechanisms of this partial protection have been discussed.
THE SITE OF SYNTHESIS OF THE 19S γ-GLOBULINS IN DYSGAMMAGLOBULINEMIA
Authors: Cruchaud Andre , Rosen Fred S. , Craig John M. , Janeway Charles A. , Gitlin David
Published: June 2004

Lymph nodes and splenic tissue from patients with congenital agammaglobulinemia and dysgammaglobulinemia and from normal subjects were studied with the use of immunofluorescence and histochemical stains to determine the site of synthesis of the 19S γ1-globulins. The two patients with dysgammaglobulinemia had high serum concentrations of the 19S γ1-globulins and a marked deficit of the 7S γ-globulins. These patients, as well as agammaglobulinemic children, had only rare or no plasma cells in their tissues. Cells were identified in sections of spleen from a dysgammaglobulinemic child as well as from normal individuals which exhibited specific fluorescence with an anti-19S γ-globulin antiserum adsorbed with 7S γ2-globulins and which stained positively with PAS and methyl green pyronine. These cells resembled the transitional cells described by Fagraeus.
ANTIBODY-PRODUCING CAPACITY OF ADULT CHICKEN SPLEEN CELLS IN NEWLY HATCHED CHICKS
Authors: Papermaster Ben W. , Bradley S. Gaylen , Watson Dennis W. , Good Robert A.
Published: June 2004

1. To evaluate the effect of primary in vitro antigenic stimulation on a population of immunologically competent cells, a homologous cell transfer system was used, with adult chickens as the spleen cell donors, killed Brucella abortus as the antigen, and newly hatched chicks as the recipients.

2. The distribution of antibody titers in recipients of cells from random donors was bimodal, with about 30 per cent showing no detectable titer and the remainder distributed normally.

3. Variability of titer was reduced significantly in subgroups receiving cells from a single donor, indicating that the primary source of variability was the genetic capacity of discrete cell populations to respond to antigen.

4. In serial passage studies, activity of donor cell populations was lost rapidly: antibody was not demonstrated after the second passage, and the graft versus host reaction (splenomegaly) was not demonstrated after the third passage. Results were similar with in vitro antigenic stimulation at the time of the first passage only and with additional stimulation at the time of subsequent transfers.

5. The thesis that,the homograft reaction of the newly hatched recipients had contributed significantly to the variability in the single transfer studies and to the rapid loss of activity in the serial transfer experiments was confirmed by the results of transfers following alteration of the lymphoreticular system of the host by thorotrast administration, splenectomy, and treatment with 19-nortestosterone during embryogenesis. All three favored the survival and function of transferred cells, raising the average antibody titer and virtually eliminating the no-response category. The inhibition of homograft immunity was most pronounced in the 19-nortestosterone group.
THE COMPLEMENT-DEPENDENT BACTERIOLYTIC ACTIVITY OF NORMAL HUMAN SERUM
Authors: Wardlaw Alastair C.
Published: June 2004

The bacteriolytic activity of normal human serum on a rough strain of E. coli has been studied by a turbidimetric method.

Bacteriolysis was found to be markedly dependent on ionic strength and pH, with optima at µ = 0.06 and pH 8.3–8.5, respectively. The method of cultivating the cells also influenced the rapidity of lysis.

Lysis was temperature-dependent and was exhibited by all samples of human serum tested. Microscopically, organisms incubated with serum were observed to swell, loose their rod shape and eventually burst, leaving remnants of the cell membrane in suspension. Sphaeroplasts were obtained by brief exposure of cells to serum followed by dilution into 5 per cent sucrose.

The bacteriolytic reaction was shown to require complement. No definite requirement for properdin or specific antibody in this system could be demonstrated by the absorption of serum with zymosan and with homologous cells respectively. The latter procedure was found to reduce bacteriolytic activity by removal of serum lysozyme. Absorption of serum with bentonite also led to loss of bacteriolytic activity which could be restored with lysozyme. The organism was not lysed by lysozyme alone, but lysis occurred with lysozyme + EDTA in tris buffer.

The possibility of complement acting independently of antibody or properdin, in certain instances, is discussed in relation to bacterial cell wall structure. Data are presented supporting the hypothesis that the "substrate" of complement in cell membranes is a lipid or lipoprotein.
PRIMARY IMMUNIZATION OF LYMPH NODE CELLS IN MILLIPORE CHAMBERS BY EXPOSURE TO HOMOGRAFT ANTIGEN
Authors: Dvorak Harold F. , Waksman Byron H.
Published: June 2004

Normal Dutch rabbit lymph node and spleen minces, lymph node cell suspensions, and residues from lymph node cell suspensions were cultured in Millipore chambers with slices of autologous or homologous (New Zealand) ear skin. for varying time intervals. Lymphoid cells exposed to New Zealand ear skin for more than 4 days were found capable of producing typical "transfer reactions" in the specific New Zealand ear skin donor, similar in every way to reactions produced by cells from lymph nodes sensitized in the intact Dutch animal. Heat-killed cells and cells exposed to New Zealand ear skin for less than 4 days (in chambers or in the intact animal) or to Dutch ear skin for any period of time were incapable of eliciting such reactions. It is concluded that normal lymphoid tissues undergo primary sensitization when exposed to homografts in Millipore chambers for suitable periods of time.
LACK OF SPECIES SPECIFICITY OF ANTIBODY TO AN ENZYME
Authors: Bollet Alfred Jay , Davis John S. , Hurt John O.
Published: June 2004

Antibodies to crystalline bovine hepatic L-glutamic dehydrogenase were induced in rabbits. These antibodies inhibited the bovine glutamic dehydrogenase used as antigen, and also inhibited glutamic dehydrogenases from rat, rabbit, human, pigeon, and frog livers, as well as frog renal and muscle glutamic dehydrogenase. The antibody did not inhibit yeast glutamic dehydrogenase which differs from the animal enzymes in cofactor requirement. The kinetic characteristics of the inhibition of the bovine glutamic dehydrogenase indicate mixed competitive and non-competitive inhibition, suggesting reaction with multiple antigenic sites; the data indicate competitive inhibition of the enzyme from other species, suggesting reaction with the catalytic site.
ANALYSIS OF THE EXPERIMENTAL LESION OF CONNECTIVE TISSUE PRODUCED BY A COMPLEX OF C POLYSACCHARIDE FROM GROUP A STREPTOCOCCI
Authors: Schwab John H.
Published: June 2004

Specific antibody and a glucosaminidase enzyme react with the serologically active sites on C polysaccharide, and local injection of these reagents will neutralize the toxic effect of C polysaccharide complexes even after an interval of 24 to 72 hours.

The cell wall lysins in S. albus filtrate and from phage-lysed Group C streptococci, break down the cell wall structure of Group A streptococci but leave the serological reactive sites of the C polysaccharide intact. These reagents lose much of their ability to neutralize the C polysaccharide toxin when superinjected after an interval of 4 hours following toxin injections.

Toxic C polysaccharide cannot be recovered from an injection site by intercellular perfusion of the excised skin area after an interval of 1 to 4 hours following toxin injection.

It is concluded that toxic particles of C polysaccharide complexes combine firmly with the dermal tissue of rabbits within 1 to 4 hours following intracutaneous injection. The cell wall lysins neutralize the toxin by reducing the particle size of C polysaccharide complexes. This minimum particle size is required for the initial reaction with tissue and when this has occurred these reagents are no longer able to influence the development of the lesion.
COLLAGEN METABOLISM IN OSTEOLATHYRISM IN CHICK EMBRYOS: SITE OF ACTION OF ß-AMINOPROPIONITRILE
Authors: Smiley J. Donald , Yeager Henry , Ziff Morris
Published: June 2004

Chick embryos were sacrificed at intervals after simultaneous injection of BAPN and proline-C14, the collagen separated into neutral salt-extractable and residue fractions, and total hydroxyproline and hydroxyproline specific radioactivity determined in each fraction. Extractable collagen, measured as hydroxyproline, increased markedly and had a higher specific activity in BAPN-treated embryos than in corresponding controls. Hydroxyproline of the residue collagen in the treated animals, however, had a lower specific activity.

When proline-C14 was injected 24 hours prior to BAPN, the specific radioactivity of the soluble collagen of treated embryos was similar to that of controls, in spite of the fact that the specific activity of the residue fraction was higher than that of the soluble fraction at the time of BAPN administration.

These results suggest that the increased amount of soluble collagen in lathyrism induced by administration of BAPN does not arise from the collagen insoluble prior to administration of the drug, but rather that BAPN acts by blocking the formation of mature collagen fibers, perhaps by preventing the formation of cross-linkages between α-collagen chains.
AN INTRACELLULAR DEFECT IN PROTEIN SYNTHESIS INDUCED BY CARBON TETRACHLORIDE
Authors: Smuckler Edward A. , Iseri Oscar A. , Benditt Earl P.
Published: June 2004

The morphological and certain metabolic effects of carbon tetrachloride intoxication were studied in the rat with emphasis on liver alterations. Morphological changes were investigated by histological and electron microscopical means. Functional changes were investigated using histochemical and amino acid incorporation, techniques. The liver constituents were examined chemically. Plasma volume alterations were measured using dye and homologous protein dilution techniques.

The histological appearance of the liver of treated animals included cellular swelling, dispersal of the cytoplasmic basophilia, and necrosis. Electron micrographs showed an early (3 hours following carbon tetrachloride administration) and widespread dislocation of the ribonucleoprotein particles from the membranes of the rough endoplasmic reticulum, but no apparent alteration in the mitochondrial structure. Histochemical examination of two mitochondrial enzyme systems, α-ketoglutarate dehydrogenase and succinic dehydrogenase, revealed no alterations in activities until a later time (6 to 12 hours following carbon tetrachloride administration). ATPase showed a gross quantitative decrease in activity at 6 and 12 hours, but not earlier.

There was a decreased amino acid incorporation into two liver-produced proteins, viz., albumin and fibrinogen. This decrease is not explicable on the basis of the inability of the liver to take up the amino acid, an altered dilution volume into which the amino acid or formed protein is placed, or an impaired capacity of the liver to excrete protein once formed. It is concluded that the decreased amino acid incorporation rate reflects depressed synthesis of protein by the liver. Other pathological changes in the liver, including necrosis, fatty change, and mitochondrial alterations may be dependent upon severe impairment of protein synthesis.
STUDIES ON THE MODE OF ACTION OF LATHYROGENIC COMPOUNDS
Authors: Levene C. I.
Published: June 2004

The lathyrogenic effect of INAH in the chick embryo may be measured by the increase in the extractibility of collagen from the bones with 1 M NaCl. Incubation of these bones in vitro with carbonyl compounds diminishes the amount of extractible collagen; with D-L-glyceraldehyde the reversal of the INAH effect is complete. This reversal effect is dependent on the time and temperature of incubation and on the quantity of D-L-glyceraldehyde, but is independent of the pH of the incubating medium, the optical form of the glyceraldehyde, or the metabolism of the cells; this suggests that it depends on a simple chemical combination. D-L-glyceraldehyde also reverses completely the extractibility of collagen from the bones of embryos rendered lathyrogenic with BAPN, semicarbazide, and hydrazine hydrate.

The hypothesis has been advanced "that lathyrogenic agents act by blocking carbonyl groups on the collagen molecule, thus preventing cross-linking essential to normal maturation; normal maturation may be restored by the addition of carbonyl groups which act by competing either for the lathyrogen or for functional sites on the collagen molecule."

In support of this hypothesis, it has been shown that purified lathyritic guinea pig collagen takes up lesser amounts of 2,4-dinitrophenylhydrazine—a compound which combines with carbonyl groups—than does normal collagen; it has been shown that lathyritic collagen still possesses the ability to form segment-long-spacing (SLS) collagen, but that these fibres are much thinner than normal; this is due perhaps to blockade of groups essential for lateral cross-linking of the tropocollagen unit.

It has also been shown that normal, purified guinea pig collagen which has been pretreated with INAH, takes up lesser amounts of 2,4-dinitrophenylhydrazine and forms much thinner SLS fibres than the untreated controls.
ROLE OF THE THYMUS IN IMMUNE REACTIONS IN RATS
Authors: Waksman Byron H. , Arnason Barry G. , Janković Branislav D.
Published: June 2004

In rats thymectomized at birth, there was a profound depletion of small lymphocytes in various lymphatic organs. In the spleen, these cells were completely lacking from the Malpighian bodies and splenic white pulp. Empty reticular structures remained surrounding the white pulp arterioles. In the lymph nodes, large masses and nodules of small lymphocytes (primary lymphoid nodules) were either markedly depleted or absent, as were the zones of these cells normally surrounding germinal centers. In both spleen and nodes, germinal centers appeared normal in size, number, and cellular make-up; and plasma cells were found in normal or even increased number in their customary position. Rats which in spite of thymectomy developed intense Arthus or delayed reactivity showed incomplete depletion of the lymphoid tissue. It is concluded that small lymphocytes of the spleen and lymph nodes may come, in large part, directly from the thymus and are not derived from medium and large lymphocytes of the germinal centers. It is suggested that there may be a second population of small lymphocytes whose function is unrelated to the thymus lymphocytes.
URINARY CALCULI IN GERMFREE RATS
Authors: Gustafsson Bengt E. , Norman Arne
Published: June 2004

In a colony of germfree rats 50 per cent of the males had urinary calculi composed of calcium citrate and calcium oxalate. Genetically closely related conventional animals on the same sterilized diet did not present a single case of stone formation. The tendency to calculus formation disappeared when germfree animals were contaminated with the intestinal flora from conventional rats.

The calculus formation can readily be explained by the high calcium, high citrate, and high pH of the urine. This pattern was changed to that of conventional rats when the germfree rats were infected with intestinal microorganisms.