bluuebunny/crossref_metadata_2025_split huggingface dataset:
CATABOLIC ORIGIN OF A BENCE JONES PROTEIN FRAGMENT
Authors: Cioli D. , Baglioni C. 
Published: June 2004

Gel filtration analysis of the urinary proteins of some patients with myeloma has shown the presence of "fragments" of Bence Jones proteins which correspond to the variable half of these proteins. Experiments have been carried out to establish the origin of a "fragment" observed in a patient who excreted a large amount of this protein. Labeled homologous Bence Jones protein has been injected into this and other control patients. Excretion of labeled "fragment" has been observed in all. Analysis by peptide mapping and radio-autography of this labeled "fragment" isolated from the urine showed that the invariable half of the Bence Jones protein was not excreted; it seemed thus likely that the invariable half was metabolized to small peptides and free amino acids.
A labeled Bence Jones protein which was excreted without any accompanying "fragment" was injected into the patient who excreted large amounts of "fragment." No excretion of labeled "fragment" was observed. It was thus concluded that the property of being degraded to "fragment" is characteristic of some "fragile" Bence Jones proteins and is not determined by the patient. Incubation with serum or urine of the "fragile" Bence Jones protein failed to produce any "fragment." "Fragments" of Bence Jones proteins are thus most likely formed during excretion of these proteins through the kidney and are products of the catabolism of Bence Jones proteins.
CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE
Authors: Mitchell G. F. , Miller J. F. A. P. 
Published: June 2004

The number of discrete hemolytic foci and of hemolysin-forming cells arising in the spleens of heavily irradiated mice given sheep erythrocytes and either syngeneic thymus or bone marrow was not significantly greater than that detected in controls given antigen alone. Thoracic duct cells injected with sheep erythrocytes significantly increased the number of hemolytic foci and 10 million cells gave rise to over 1000 hemolysin-forming cells per spleen. A synergistic effect was observed when syngeneic thoracic duct cells were mixed with syngeneic marrow cells: the number of hemolysin-forming cells produced in this case was far greater than could be accounted for by summating the activities of either cell population given alone. The number of hemolytic foci produced by the mixed population was not however greater than that produced by an equivalent number of thoracic duct cells given without bone marrow. Thymus cells given together with syngeneic bone marrow enabled irradiated mice to produce hemolysin-forming cells but were much less effective than the same number of thoracic duct cells. Likewise syngeneic thymus cells were not as effective as thoracic duct cells in enabling thymectomized irradiated bone marrow-protected hosts to produce hemolysin-forming cells in response to sheep erythrocytes.
Irradiated recipients of semiallogeneic thoracic duct cells produced hemolysin-forming cells of donor-type as shown by the use of anti-H2 sera. The identity of the hemolysin-forming cells in the spleens of irradiated mice receiving a mixed inoculum of semiallogeneic thoracic duct cells and syngeneic marrow was not determined because no synergistic effect was obtained in these recipients in contrast to the results in the syngeneic situation. Thymectomized irradiated mice protected with bone marrow for a period of 2 wk and injected with semiallogeneic thoracic duct cells together with sheep erythrocytes did however produce a far greater number of hemolysin-forming cells than irradiated mice receiving the same number of thoracic duct cells without bone marrow. Anti-H2 sera revealed that the antibody-forming cells arising in the spleens of these thymectomized irradiated hosts were derived, not from the injected thoracic duct cells, but from bone marrow.
It is concluded that thoracic duct lymph contains a mixture of cell types: some are hemolysin-forming cell precursors and others are antigen-reactive cells which can interact with antigen and initiate the differentiation of hemolysin-forming cell precursors to antibody-forming cells. Bone marrow contains only precursors of hemolysin-forming cells and thymus contains only antigen-reactive cells but in a proportion that is far less than in thoracic duct lymph.
QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS
Authors: Wilson Darcy B. , Blyth Janet L. , Nowell Peter C. 
Published: June 2004

The proliferative interaction of cultured rat lymphocytes of immunogenetically disparate origin—the mixed lymphocyte interaction—was employed as an experimental model to examine the initial stages of the immune response mechanism. Using mixed cultures of cells derived from parental strain and F1 hybrid rats, in which only the parental lymphocytes respond, the following observations were made on the magnitude and kinetics of the reaction.
After initiation of the cultures, there was a latent period of approximately 40 hours during which time no mitotic activity was detected.
This inactive phase was followed by a period of proliferation in which previously nondividing cells entered the mitotic cycle for the first time. Activity in the cultures, as detected by incorporation of radioactive thymidine and measured by radioautography or scintillation spectrometry, increased exponentially with a doubling time (T2) of 9–10 hr.
In this exponential proliferative phase, lasting approximately 100 hr, the dividing cells underwent a series of rapid sequential divisions with a generation time (Tc) of 8 hr, and few, if any, dropped out of the mitotic cycle.
In addition to the cells which first entered mitosis at the beginning of the proliferative phase and then proceeded through multiple divisions, significant numbers of new, previously nondividing cells continued to enter the mitotic cycle during the entire exponential growth phase. The total number of these newly responsive, first division cells throughout the total culture period amounted to 1–3% of the original parental cell inoculum. This is a surprisingly large proportion of peripheral blood lymphocytes with demonstrable reactivity to a particular antigen system, if it is assumed that these first division cells in vitro are functionally related to the hypothetical antigen-sensitive cells which proliferate and differentiate into immunological effector cells. At present there is no entirely satisfactory explanation for this large number of reactive cells in the mixed lymphocyte interaction.
THE INDIVIDUAL ANTIGENIC SPECIFICITY OF ANTIBODIES TO STREPTOCOCCAL CARBOHYDRATES
Authors: Braun Dietmar G. , Krause Richard M. 
Published: June 2004

Although a single electrophoretically uniform antibody component with specificity for the group carbohydrate may comprise the bulk of the γ-globulin in rabbits immunized with streptococcal vaccines, this is not always the case. Not infrequently, electrophoresis may reveal multiple antibody components. Nevertheless, it has been feasible by various preparative procedures to isolate from a single antiserum at least two antibody components with similar reactivity for the carbohydrate both of which are electrophoretically monodisperse. Light chains from such antibodies reveal a restricted pattern when examined by disc electrophoresis.
Antibodies to streptococcal carbohydrates have been examined for their individual antigenic specificity. Goats were immunized with isolated Group C and Group A-variant antibodies raised in rabbits. Individual antigenic specificity of these antibodies was brought out by absorption of the goat anti-antiserum with Fr II of pooled normal rabbit sera. Additional absorption of the goat anti-antisera with Fr II diminished but did not eliminate the reactivity for the homologous antibody.
Immunoelectrophoretic studies with papain fragments of purified streptococcal antibodies localized the specificity to the Fab fragment. Specificity was not confined to the isolated light chains of the antibody.
A SUBCLASS OF HUMAN γA-GLOBULINS (γA2) WHICH LACKS THE DISULFIDE BONDS LINKING HEAVY AND LIGHT CHAINS
Authors: Grey Howard M. , Abel Carlos A. , Yount William J. , Kunkel Henry G. 
Published: June 2004

The γA2-subgroup of γA-globulins, previously delineated by antigenic studies, was found to differ strikingly from other immunoglobulins in the manner in which the polypeptide chains are bound together. The heavy and light chains were not linked to each other by disulfide bonds. Instead the light chains were disulfide linked to one another, and were present in the γA2-molecule as disulfide bridged L-L dimers.
Antisera specific for γA2-proteins indicated the occurrence of two different antigenic types in all normal sera as well as saliva and colostrum. Both of these showed the unique interchain disulfide linkage. Quantitative analyses indicated higher levels of γA2-proteins in external secretions.
HISTOPATHOLOGICAL EFFECTS IN MICE OF HETEROLOGOUS ANTILYMPHOCYTE SERUM
Authors: Taub Robert N. , Lance Eugene M. 
Published: June 2004

The effects of heterologous rabbit anti-mouse lymphocyte antiserum on the morphology of lymphoid and other tissues was investigated in CBA mice.
The lymphoid tissues exhibited characteristic changes specific for ALS treatment, which were an invariable accompaniment to its immunosuppressive effects. These consisted of peripheral lymphopenia occurring at some time during a course of ALS treatment and persistent depletion of small lymphocytes in lymph node paracortical areas and splenic follicular periarteriolar zones. The thymic histology was generally well preserved.
It is suggested that the relevant lesions reflect a rapid depletion of the pool of recirculating lymphocytes, possibly by a primary cytotoxic effect exerted on cells peripheral to lymphoid tissue.
Other histologic features attendant to the administration of ALS were accounted for as consequences of immunization of ALS recipients to rabbit serum constituents or by the deleterious effects of antibodies directed against tissues other than lymphoid cells.
CELLULAR DIFFERENTIATION AND THE AGING PROCESS IN CARTILAGINOUS TISSUES
Authors: Shulman Herbert J. , Meyer Karl 
Published: June 2004

Primary cell cultures of differentiated chondrocytes were shown to produce chondroitin-4-sulfate as the predominant mucopolysaccharide, with suggestive evidence for the synthesis of keratan sulfate and possibly chondroitin-6-sulfate.
Chicken embryonic cartilage was shown to be composed mainly of chondroitin-4-sulfate, with a small amount of chondroitin-6-sulfate, but essentially no keratan sulfate.
These findings were compared to the data of others, and a hypothesis explaining the aging process in cartilage in terms of cellular differentiation was presented.
STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS
Authors: Macher Egon , Chase Merrill W. 
Published: June 2004

In light of knowledge of the rate and route of dispersal of allergenic chemicals from ear sites (0.25 µg of picryl chloride, or 2:4 dinitrochlorobenzene in 0.25 µg and 5.0 µg amounts), dispersal was interrupted at selected times by ear excision. The animals exposed in this manner to different, tiny amounts of allergen were tested for development of contact type hypersensitivity.
Both of these allergenic chemicals left the local ear site in about three phases of successively lengthening "half-lives." In the first phase, the escape rate was high. The principal pathway of escape was not via the lymphatics but via the blood vessels. Ear excisions made at 24 hr after injection of 0.25 µg of picryl chloride (PCl) or at 12 hr after injection of 5.0 µg of dinitrochlorobenzene (DNCB) essentially blocked onset of delayed type hypersensitivity, hence the first fraction to escape (80% of PCl, 98% of DNCB) was not used for sensitization. This large fraction serves rather to set up a state of specific tolerance, for these individuals showed extensive deficits in their ability to respond to a later sensitizing course. Also the ability to form hapten-specific antibody appeared nearly completely suppressed. Injections of allergen into the blood stream or directly in auricular nodes, in an amount approximating that which escaped early from the ear, also led to the same degrees of unresponsiveness—sometimes full, sometimes partial tolerance. The same types of specific tolerance were secured also by injecting subsensitizing doses into the ear, without excision, or into the flank and by contact tests applied to the flank.
The allergen remaining in the ear after the early outflow, particularly between 12–24 hr and 3–4 days, appeared to constitute the sensitizing depot. The longer this depot was available to the animals the greater the immunological "information" for sensitization was picked up until the depot had served its full function around the 4th day. "Peripheral sensitization" was clearly demonstrable.
The eventual degree of sensitivity attained by the animals was a resultant of two immunologic processes which occurred independently—tolerogenic effects of escaped chemical on the one hand and on the other the sensitizing effect of the local sensitizing depot of allergen bound in the ear tissue.
IMMUNOLOGICAL INDUCTION OF INCREASED VASCULAR PERMEABILITY
Authors: Henson P. M. , Cochrane C. G. 
Published: June 2004

Passive cutaneous anaphylaxis (PCA) reactions were produced in rabbits by antibodies to bovine serum albumin. Two types of antibodies were found, each inducing increased vascular permeability, but by means of different mediation systems.
One of these antibodies required the presence of complement, platelets, and neutrophils for the induction of the PCA reaction, which was inhibited by antihistamine. This antibody was heat stable, sedimented in the 7S region, and was found in both fast and slow electrophoretic fractions of rabbit γ-globulin.
Homocytotropic antibody was also detected. The PCA reactions induced by this type of antibody did not require platelets or neutrophils and were not inhibited in rabbits depleted of C3 with cobra venom factor. The lesions were, however, prevented by administration of antihistamine.
CELL SEPARATION ON ANTIGEN-COATED COLUMNS
Authors: Wigzell Hans , Andersson Birger 
Published: June 2004

Glass and plastic bead columns coated with antigenic protein molecules were used as an immunological filter for cell populations containing immune cells of relevant specificity. A selective elimination of these immune cells from the passing cell suspension was regularly noted and it approached, in some experiments, complete abolition of the specific immune reactivity of the filtered cell population. This specific retention of immune cells by antigenic columns could be selectively blocked by the presence of free antigen molecules in the medium during filtration. The results obtained support the concept of a cell-associated antigen-specific receptor being present on the outer surface of immune cells, displaying the same antigen-binding specificity as the potential product of the cell, the humoral antibody. Using the present bead column system, results were obtained indicating that this receptor was an active product of the immune cells and not any passively adsorbed, cytophilic antibody.
Antigenic bead columns may very well constitute a tool for the production in vitro of cell populations being specifically deprived of immune reactivity and allow detailed analysis of the characteristics of the cell-associated antibody of immune cells.
LYSOSOMAL AND ULTRASTRUCTURAL CHANGES IN HUMAN "TOXIC" NEUTROPHILS DURING BACTERIAL INFECTION
Authors: McCall Charles E. , Katayama Isao , Cotran Ramzi S. , Finland Maxwell 
Published: June 2004

"Toxic" neutrophils from humans with severe bacterial infections, identified by the presence of Döhle bodies, "toxic" granules, and vacuoles were shown to differ from normal neutrophils both in ultrastructure and in lysosome activity.
Döhle bodies were identified as lamellar aggregates of rough endoplasmic reticulum. Toxic granules corresponded to the azurophilic granules usually identified by Romanowsky stains only in neutrophil precursors. By electron microscopy such granules were large, electron-dense, and peroxidase positive; they could usually be distinguished from the smaller, less dense, "specific" granules also present in control neutrophils, but in the latter they became visible by light microscopy only after prolonged staining or following fixation with glutaraldehyde. These observations suggest that toxic granules represent an abnormal staining reaction of the large dense granules in the toxic cells, and not phagocytized material, newly formed abnormal granules or autophagic bodies.
Alkaline phosphatase activity was significantly greater in toxic neutrophils than in normal ones; 80% of the activity of both was located in the lysosome fraction. Beta glucuronidase was normal. Total acid phosphatase was normal, but the percentage located in the nonlysosome fraction of toxic neutrophils was increased, suggesting that lysosomes were "labilized."
Formation of neutral red vacuoles in supravitally stained preparations, an index of lysosome activity, occurred more rapidly in toxic neutrophils. This reaction paralleled degranulation and the formation of clear vacuoles in unstained wet mounts and could be blocked by colchicine, a lysosome stabilizer, or enhanced by procedures which activate lysosomes. "Autophagic" vacuoles were observed by electron microscopy in some toxic neutrophils.
These observations are discussed in relation to the concept that the "toxic" neutrophils in severe bacterial infection reflect cellular immaturity and/or stimulation or degeneration.
IMMUNOCHEMICAL STUDIES OF FOOT-AND-MOUTH DISEASE
Authors: Cowan K. M. 
Published: June 2004

Three antigenic variants of foot-and-mouth disease virus, type A, strain 119, were demonstrated in Ouchterlony analyses utilizing serum collected from guinea pigs 7 days postinfection (DPI). Such antisera contain antibodies of the 19S class. Guinea pig antisera that contained antibodies of the 7S class were unable to distinguish between the antigenic variants. Similarly, 19S antibody was able to demonstrate antigenic differences in trypsin- and chymotrypsin-treated viruses that were not detected by 7S antibody-containing antisera.
One of the antigenic variants of virus is apparently the wild type and is tentatively considered to have two antigenic determinant groupings termed the a- and b-sites (140S-ab). The 140S-ab variant was the sole or predominant antigenic type produced in guinea pigs and in large plaque-forming- and tissue culture-low passage sources of the virus. Another antigenic variant appears to possess only the b-site (140S-b) and was the major constituent in tissue culture-high passage virus preparations. The third variant, a small plaque former, was also devoid of the a-site and contains an antigenic determinant that is related to, but not identical with, the b-site. This variant appears to be a minor constituent of tissue culture-high passage virus.
7-DPI serum could be absorbed with a suitable concentration of tissue culture-high passage virus to remove antibody reactive with the b-determinant site. This absorbed serum still precipitated 140S-ab virus by virtue of still containing antibody reactive with the a-determinant site; however, the neutralizing activity was eliminated. This suggests that the b-site is critical with respect to neutralization while the a-site is noncritical.
ANTIGEN-REACTIVE CELLS IN NORMAL, IMMUNIZED, AND TOLERANT MICE
Authors: Armstrong W. D. , Diener E. , Shellam G. R. 
Published: June 2004

The numbers of antigen-reactive cells (ARC) responding to a purified protein, the polymer of S. adelaide flagellin, have been assayed in cell populations derived from several lymphoid tissues of mice. The assay, which employs the cell transfer into lethally irradiated mice, indicates that there is a response of ARC in bone marrow in the absence of thymus cells. This suggests that the immune response to this protein antigen is not thymus dependent.
The presence of relatively large numbers of ARC in Peyer's patches argues for their direct participation in the immune response in the adult mouse.
The kinetics of ARC and antibody-forming cells in the early primary response employing the transfer system is described. The numbers of ARC declined during the first 2 days of the immune response, but by day 6 had increased to about five times the number in unprimed spleen cells. The rise is believed to be a result of the primary injection of antigen and therefore may be described as memory; however, these experiments have not been able to further elucidate any specific qualities of the "memory cell."
Tolerance induction in C57BL/Brad mice produced by repeated injections of a cyanogen bromide digest of the antigen is described. The ARC or its precursor is shown to be the site of the lesion of tolerance by direct investigation.
THE BACTERIAL INDUCTION OF HOMOGRAFT SENSITIVITY
Authors: Rapaport Felix T. , Markowitz A. S. , McCluskey Robert T. 
Published: June 2004

Immunization of rabbits with Group A Type 12 streptococcal cell membranes has elicited serum antibodies which have the ability to cause rapid rejection of skin allografts in guinea pigs. Intradermal injection of such antisera has resulted in skin reactions characterized by prominent polymorphonuclear leukocyte infiltrates, similar to those noted in the Arthus reaction. The combined use of membrane antisera and epinephrine has resulted in hemorrhagic necrosis of the skin of guinea pigs.
The ability of membrane antisera to exert these effects appears to be dependent upon the presence in the host tissues of antigen(s) shared by or cross-reacting with streptococcal membrane antigens. Such cross-reacting antigens may have a group distribution in the outbred guinea pig population.
The results highlight the potential biological importance of antigens present in the Group A streptococcal membrane in the induction of altered tissue reactivity in the mammalian host.
STUDIES ON THE ENTRY OF VIRUSES INTO THE CENTRAL NERVOUS SYSTEM OF MICE VIA THE CIRCULATION
Authors: Sellers Margret I. 
Published: June 2004

The inhalation of CO2 exerted a selective action on the entry of viruses into the CNS of mice via the circulation. In 6 wk old animals, the infectivity of poliovirus, vaccinia, and vesicular stomatitis viruses was enhanced, whereas the entry of herpesviruses and of a neurotropic influenza virus was not affected. However, in 3 to 4 wk old mice, inhalation of the gas enhanced the infectivity of all the viruses. To explain the relationship of age to the animals' response to CO2, it was proposed that CO2 inhalation, by increasing the rate of cerebral blood flow, served to increase the exposure of some extraneural cell(s) to virus, possibly the cerebrovascular endothelial cell, in which virus replicated and reached the brain parenchyma by direct extension of the infectious process. Consequent to maturation, the postulated target cell developed resistance to certain viruses, while its susceptibility to others remained unchanged.
Inoculation of adrenalin or serotonin simultaneously with virus into the circulation enhanced the CNS infectivity of all the viruses tested in both 4 wk and 6 wk age groups of mice. The enhancing effects were completely inhibited by the action of an α-adrenergic blocking agent; it was therefore concluded that hemodynamic changes produced by the contractile response of the smooth muscle cells in the vessel walls mediated the enhancing effect. It was suggested that a vasopressor response invoked in the peripheral vessels, with a consequent increase in cerebral blood flow, increased virus dosage to the CNS. In addition, a direct effect of the vasoactive amine on the cerebral vessels, resulting in the disruption of an anatomical "barrier", was considered as a contributory factor in increasing the transfer of virus to the CNS from the circulation.