bluuebunny/crossref_metadata_2025_split huggingface dataset:
STRUCTURAL STUDIES OF HUMAN IMMUNOGLOBULINS
Authors: Frangione Blas , Franklin Edward C. 
Published: June 2004

1. Comparison of peptide maps of the Fc fragments of normal G immunoglobulins and 11 G myeloma proteins of the We (b) type showed them to be very similar except for differences associated with the Gm type. Some additional differences were noted, however, in the Fc fragments of three Vi (c) myeloma proteins.
2. Peptide maps of heavy chains from the same G myeloma proteins differed from each other and from normal heavy chains. In general, the myeloma chains contained a larger number of well defined spots; some of these were common to normal heavy chains while others were unique to each protein. Others, present in normal heavy chains, were lacking in the myeloma proteins.
3. Comparison of the heavy chains and Fc fragments from the same protein suggests that much of the variability of different myeloma proteins and, presumably, antibodies resides in the Fd fragment.
4. Further support for this is given by the finding that the antigenic specificity of 3 myeloma proteins also appeared to reside in the Fd fragments.
ANTAGONISTIC EFFECTS OF HUMORAL ISOANTIBODIES ON THE IN VITRO CYTOTOXICITY OF IMMUNE LYMPHOID CELLS
Authors: Möller Erna 
Published: June 2004

The ability of specifically immunized lymphoid cells to kill H-2 incompatible target tumor cells in tissue culture was shown to depend on the source of the lymphoid tissue (spleen versus lymph nodes). Marked cytotoxic effects were obtained with regional lymph node cells 7 to 10 days after primary immunization, whereas spleen cells from the same animals had little or no effect. Hyperimmunization did not decrease the cytotoxic efficiency of lymph node cells. Experiments were performed to test the possibility that the weak effect of spleen cells is a result of humoral antibody production, antagonizing the cell-bound immunity.
Humoral antibodies were cytotoxic in vitro in the presence of complement only. Their effect was manifested after 2 hours, whereas immune lymph node cells did not require complement and cytotoxicity was not expressed until 24 to 48 hours' incubation. Tumor cell cultures treated with specific humoral antibodies in the absence of complement became resistant to the cytotoxic effect of subsequently added immune lymph node cells, while no such protection was seen when normal serum was added. Thus, humoral antibodies led to an "efferent" inhibition of cell-bound immunity in vitro, in analogy with previous results in vivo.
AUTOIMMUNE DISEASE IN NZB/BL MICE
Authors: Mellors Robert C. 
Published: June 2004

This study, based upon 528 laboratory examinations and 16 complete autopsies of NZB/Bl mice, deals with autoimmune manifestations (as shown by hypergammaglobulinemia, Coombs positive hemolytic anemia, and the occasional presence of lupus- and rheumatoid-like factors) and mainly with the pathology and the pathogenesis of glomerulonephritis in these mice, a model system of membranous glomerulonephritis with spontaneous and insidious onset, progression through chronic stages, and almost certainly induced by immunological, and autoimmune, mechanisms. The earliest and lasting histological change was hyaline thickening of the capillary walls and adjacent intercapillary regions of the glomerular tufts, corresponding in location to polysaccharide-rich capillary basement membrane and mesangial materials. Distributed focally and diffusely in the glomerular tuft and eventually sparing no glomerulus, hyaline, granular, and fibrillar ("spongy fiber") materials produced narrowing of capillary lumens by concentric or eccentric encroachment upon them. In the later stages hyaline lobulation and sclerosis of the glomerular tufts occurred. Thus the lesions corresponded to those seen in human focal and diffuse membranous, chronic lobular, and lastly (intracapillary) sclerosing glomerulonephritis.
In all instances of glomerulonephritis the glomerular tufts contained selective localizations of mouse immunoglobulins corresponding in distribution to that of the hyaline and (PAS-positive) polysaccharide-rich materials in the focal and diffuse membranous and lobular lesions and in amounts increasing with the severity of glomerular disease. The mouse immunoglobulins were extracted from frozen sections of glomerulonephritic kidneys and were then capable of recombination with glomerular tufts in sections of autologous or isologous glomerulonephritic kidneys from which in vivo localized immunoglobulins had been extracted. The pattern of recombination with glomerular tufts was similar to that of in invo localized immunoglobulins. The extracted immunoglobulins did not show affinity for mouse red cells (in the indirect Coombs test) nor for autologous or isologous cell nuclei (in the immunofluorescence test). The serum of mice with severe glomerulonephritis contained immunoglobulins with in vitro affinity for extracted autologous or isologous glomerular tufts. Thus circulating as well as localized antibodies were demonstrated. The immunogenic materials (autoantigens) may have been formed in the glomerular tufts or accumulated in them from some other source, such as the circulating plasma; however they corresponded in location to polysaccharide-rich capillary basement membrane and mesangial materials.
The spleen was identified at the cellular level as the main site of formation of autoantibodies to red cells, as well as the main site of red cell destruction. Some evidence was brought forth suggesting that these autoantibodies were "heavy" or γM-globulins. More studies are in progress.
PATHOGENIC FACTORS IN VASCULAR LESIONS OF EXPERIMENTAL SERUM SICKNESS
Authors: Kniker William T. , Cochrane Charles G. 
Published: June 2004

The present studies suggest that polymorphonuclear leukocytes (PMN's) are essential for the development of cardiovascular lesions in serum sickness. In the absence of PMN's, necrotic vascular lesions were never seen and endothelial proliferation in arteries was inhibited. Zones of fibrinoid deposits did not occur. By contrast, at least two-thirds of the control animals exhibited endothelial proliferation, and half had necrosis of arterial walls, usually with fibrinoid deposits. In arterial lesions that involved the intima and media, the internal elastic lamina was disrupted. This was associated with accumulations of PMN's and was prevented when PMN's were depleted. The observations suggested that the elastic lamina acts as a barrier to the outward spread of inflammation in arteries and that it is an important substrate of PMN action. Although glomerulitis and proteinuria developed in PMN-depleted animals, no conclusions could be drawn concerning the pathogenic role of PMN's in renal lesions, since PMN depletion could not be effected before the onset of immune elimination without influencing the immune response itself.
Host complement (ß1C-globulin) was localized along with the antigen and rabbit gamma globulin in glomeruli and arteries showing lesions. In the glomeruli these deposits formed a granular lining along the area of the basement membrane. In arteries the fluorescent amorphous particles were in the intima and media of inflamed vessels.
The immune response to BSA and the incidence and severity of cardiovascular and renal lesions were enhanced by the intravenous administration of pooled rabbit antiserum to BSA given 18 hours before BSA antigen and by injecting endotoxin along with the BSA. These additions to the usual procedure of inducing serum sickness did not appear to change the quality of the disease.
In normal rabbits, the peak incidence of cardiovascular lesions was early in immune elimination of antigen, at a time when levels of circulating complexes was maximal. Conversely, the severest renal injury was noted several days later, at the completion of immune elimination.
THE ROLE OF SERUM COMPLEMENT IN CHEMOTAXIS OF LEUKOCYTES IN VITRO
Authors: Ward Peter A. , Cochrane Charles G. , Müller-Eberhard Hans J. 
Published: June 2004

By the use of chambers containing two compartments with an interposed micropore filter, chemotaxis of polymorphonuclear leukocytes (PMN's) in vitro was studied employing various agents that fixed serum complement (C'). Antigen-antibody complexes, zymosan, and aggregated human gamma globulin, in the presence of fresh rabbit, guinea pig, or mouse serum resulted in the migration of PMN's through the micropore filter. Pepsin-degraded rabbit antibody or unaltered duck serum containing antibody did not exhibit such activity after addition of antigen. Heating of the serum before treatment or the presence of EDTA prevented the generation of the chemotactic factor. The chemotactic factor could not be generated in whole serum from rabbits genetically deficient in C'. However, the defect in this rabbit serum could be corrected by addition of rabbit or human C'6. Serum of B10·D2 mice deficient in hemolytic C' also yielded poor chemotactic activity.
Interaction of the first four reacting components of guinea pig C' did not result in significant chemotactic activity unless guinea pig euglobulin with heat labile components was also present. In rabbit serum, C'5 and C'6, when "activated" by interaction with the first four reacting components, behaved like a protein-protein complex and exhibited marked chemotactic activity. By employing conditions favoring dissociation of the complex, the individual components were isolated and shown to be chemotactically inactive. Upon recombination of the two components, however, activity reappeared. Using another approach, the C'5–C'6 complex was isolated intact, and shown to be chemotactically active while other fractions not containing these components were not active. It is postulated that the C'5–C'6 complex is the active chemotactic factor generated in serum after the addition of C'-fixing agents.
ON THE ACTION OF COLCHICINE
Authors: Malawista Stephen E. 
Published: June 2004

The effect of colchicine was studied on the rapid, reversible darkening of frog skin under the influence of melanocyte-stimulating hormone (MSH). Darkening is due to dispersion of melanin granules in melanocytes and is thought to be accompanied by a gel-to-sol cytoplasmic transformation. After subsequent washing, the skin lightens, with aggregation of melanin granules and cytoplasmic gelation.
Preincubation of skin with colchicine had the following effects:
1. Darkening induced by MSH was increased in comparison to control skins, and on removal of MSH, lightening was inhibited. Inhibition was a function of both concentration (1 x 10–5 to 9 x 10–5 M) and exposure time (2 to 30 minutes). Once established, inhibition was maintained throughout the remainder of the experiment. 2. The same effects were noted (a) when darkening was effected by agents other than MSH (ATP) 0.9 x 10–3 M; caffeine, 5.2 x 10–3 M; ethyl acetate, 0.8 x 10–2 M), and (b) when lightening was effected by addition of chemical agents (melatonin, 4.3 x 10–10 M; hydrocortisone, 1 x 10–3 M; norepinephrine, 1 x 10–3 M), instead of by washing. 3. Colchicine alone produced a gradual, irreversible, dosage-dependent darkening over several hours. This darkening was inhibited by melatonin, 4.3 x 10–10 M.
The melanocyte model is used to construct a general theory of colchicine action on living cells, an action resulting in decreased protoplasmic viscosity. In this formulation colchicine lowers the potential limit of protoplasmic gelation, and does it rapidly, reversibly, in low concentration, in a dosage-dependent manner, and without killing the cell. The theory allows interpretation of "synergism" and "antagonism" to colchicine by other substances. It suggests a tentative approach to the understanding of colchicine action in acute gouty arthritis, where interference with ameboid activities of polymorphonuclear leukocytes is one possible aspect of the anti-inflammatory effect of colchicine. Finally, the colchicine-treated melanocyte is viewed as a good, live physical model that can be used to elucidate some fundamental biological properties.
THE IN VITRO DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES
Authors: Cohn Zanvil A. , Benson Belinda 
Published: June 2004

Mouse mononuclear phagocytes cultivated in 50 per cent newborn calf serum medium pinocytize actively and form large numbers of phase-dense granules as well as three hydrolytic enzymes. When such cells are then placed in 1 per cent newborn calf serum they illustrate (a) a low level of pinocytic activity, (b) a shrinkage in granule size, and (c) a loss in cell protein, acid phosphatase, ß-glucuronidase, and cathepsin. Examination of the extracellular medium revealed no detectable hydrolase activity. The reintroduction of cells into high levels of serum again resulted in granule and enzyme formation.
Cells rapidly incorporated fluorescein-conjugated calf serum proteins into the phase-dense granules. The fluorescence of labeled granules was lost during an 18 hour period in non-fluorescein-containing medium.
Crystalline egg white lysozyme was concentrated in the macrophages. Approximately 80 per cent of the cell-associated enzyme was lost during a 24 hour washout period in either 1 or 50 per cent serum medium. No enzymatic activity could be recovered in the medium.
Colloidal gold was taken up and concentrated in macrophage granules. Quantitative assays revealed this particle to be conserved during a 24 hour washout period.
HUMORAL AND CELLULAR ASPECTS OF THE IMMUNE RESPONSE TO THE SOMATIC ANTIGEN OF SALMONELLA ENTERITIDIS
Authors: Landy Maurice , Sanderson Ronald P. , Jackson Anne L. 
Published: June 2004

A study was made of the cellular and humoral aspects of the immune response of the rabbit to the somatic polysaccharide of Salmonella enteritidis. The response to a single intravenous injection was characterized by the appearance of elevated titers of bactericidal antibody between 2 and 3 days later. The maximum titer was dose-dependent and occurred between 5 and 7 days, thereafter declining rapidly during the first month. The significant stabilized levels which then persisted for at least 1 year were also dose-dependent. Most of the antibody produced (&gt;99 per cent) was associated with the macroglobulin fraction of serum.
Plaque-forming cells (PFC) elaborating antibody specific for this somatic antigen were detected and enumerated by the technique of localized hemolysis in gel employing polysaccharide-coated sheep erythrocytes. Significant numbers of PFC were encountered in the spleen as early as 14 to 18 hours after a single intravenous injection of antigen; after 36 hours the number of PFC rose rapidly and culminated in a maximum population at 5 days, followed by a rapid decline and plateau similar to that for circulating antibody. The spleen was the principal organ involved in the systemic response, but other lymphoid tissues including bone marrow, peripheral blood leucocytes, and thymus contributed significantly.
After an interval of 3 months the effect on humoral antibody titers of a second injection of antigen was dependent on the amount of polysaccharide administered; markedly greater titers were now obtained with 0.02 to 0.002 µg, whereas 0.2 to 20 µg resulted in a duplication of the initial humoral response. The cellular response to a second dose of 5 µg was accelerated; larger numbers of PFC appeared more rapidly, attained a maximum population by day 3, and exceeded the primary response by a factor of two. This acceleration in the attainment of maximum numbers of PFC and the increased bactericidal antibody titers following a second injection of limiting amounts of antigen suggest that these somatic polysaccharides may in fact evoke a "secondary" type of response in the rabbit.
HOMOGRAFT IMMUNITY IN PREGNANCY
Authors: Lanman Jonathan T. , Herod Llewellyn 
Published: June 2004

The mammalian fetus affixed to the uterine wall in some ways resembles a homograft, but maternal homograft immunity even when specifically directed against her fetuses fails to destroy them. The placental barrier appears to be critical in protecting the fetus against maternal immunologic attack. In order to evaluate the means by which it affords protection, we have measured in rabbits the transfer of cytotoxic antibody from mother to fetus. When the offspring were not the specific targets for maternal antibody, we found titers of cytotoxic antibody in the newborn animals at or near maternal levels in 16 of 18 cases (89 per cent), demonstrating the ability of this antibody to cross the rabbit placenta. When the offspring were appropriate targets for antibody, however, 11 of 18 newborn animals (61 per cent) had no demonstrable titer. We believe that in these latter cases, antibody had become fixed to antigenic sites and thereby had been removed from the fetal circulation. There was, however, no evidence of harm to any of the fetuses, either in survival (as demonstrated in a previous study) or in spleen or thymus weights or peripheral leukocyte and mononuclear cell counts.
Cytotoxic antibody appears to reach the embryo early in gestation, since we found antibody in 8-day-old blastocyst fluid in each of 2 trials.
We conclude that the fetus neither receives nor requires protection against cytotoxic antibody, and believe that fetal protection against maternal homograft immunity is afforded by a placental barrier to maternal mononuclear leukocytes.
THE EFFECTS OF THYMUS AND OTHER LYMPHOID ORGANS ENCLOSED IN MILLIPORE DIFFUSION CHAMBERS ON NEONATALLY THYMECTOMIZED MICE
Authors: Osoba David 
Published: June 2004

When neonatally thymectomized CBA mice were implanted at 9 to 12 days of age with Millipore diffusion chambers (pore size, 0.1 µ) containing either syngeneic or allogeneic neonatal thymus, they were subsequently found to have the capacity to reject skin homografts and to form antibodies to sheep erythrocytes. In spite of displaying restored immune reactivity, thymectomized mice bearing thymus-filled diffusion chambers still had a lymphopenia and diminished numbers of small lymphocytes in their spleens, lymph nodes and Peyer's patches. Comparison of the lymphoid organs of these mice with those of the thymectomized control mice did not reveal any appreciable difference in the numbers of primary follicles or small lymphocytes. It is postulated that the thymus humoral factor induced immunological competence in lymphoid cells which had left the thymus prior to neonatal thymectomy. The paucity of circulating and tissue small lymphocytes in thymectomized animals, the immune reactivity of which was restored by thymus tissue in diffusion chambers, argues against the theory that the thymus humoral factor has a lymphocytosis-stimulating effect.
There was no restoration of immune reactivity in those neonatally thymectomized mice which had been implanted with diffusion chambers containing neonatal or adult spleens, or adult lymph nodes. Thus, the competence-inducing factor is elaborated by the thymus but not by the spleen or lymph nodes.
Allogeneic (C57Bl) neonatal thymus tissue, enclosed within diffusion chambers, had the capacity to restore the immune reactivity of totally thymectomized CBA mice, not only to skin homografts of a totally unrelated strain (Ak), but also to grafts isogeneic with the donor of the allogeneic thymus. Therefore, there is no strain barrier to the action of thymus humoral factor.
To explain the apparent lack of full participation of thymus lymphocytes in immune reactions it is postulated that thymus lymphocytes are functionally immature in situ, and that they leave the thymus before attaining immunological competence. In the periphery, they undergo further maturation under the influence of the competence-inducing factor produced by the thymus.
COLONIZATION OF THE MOUSE INTESTINE WITH ESCHERICHIA COLI
Authors: Mushin Rose , Dubos Rene 
Published: June 2004

Young albino Swiss mice, of the NCS and NCS-D colonies, proved highly susceptible to the establishment of intestinal infection with an enteropathogenic strain of E. coli administered per os or by stomach tube.
The period of highest susceptibility was rather short, extending from the day of birth to approximately 2 weeks of age. Adult NCS and NCS-D mice failed to become experimentally colonized with E. coli, even when large doses were administered per os on 3 consecutive days.
The extent of colonization of the various parts of the gastrointestinal tract was related to the size of the infective dose. Many of the young mice died within 2 to 3 days following per os infection with large doses of enteropathogenic E. coli. However, practically all the animals which survived cleared their intestinal infection at approximately the same age. For example, in mice infected with 23 x 106 bacteria, colonization of the intestinal tract usually came to an abrupt end when the animals were 24 to 28 days old, irrespective of the age at which they had been infected.
There is suggestive evidence that the acquisition of resistance with age, and the ability of adult animals to control the intestinal infection, are related to the development in the gastrointestinal tract of a microbiota which is antagonistic to E. coli.
DISTRIBUTION AMONG THE γ-GLOBULIN MOLECULES OF DIFFERENT GENETICALLY DETERMINED ANTIGENIC SPECIFICITIES IN THE GM SYSTEM
Authors: Mårtensson Lars , Kunkel Henry G. 
Published: June 2004

Isolated myeloma proteins and anti-Rh antibodies were utilized for determination of the distribution among the γ-globulin molecules of various Gm(b) and Gm(f) determinants. All of these genetic factors are as a rule inherited together in Caucasians, but not in other races. The Gm(b) determinants, except (b2), were found together in the same Caucasian myeloma globulins of the Vi H chain group, which never carried Gm(f) or (b2). The Gm(f) and (b2) determinants were found together in other myeloma globulins, of the We group. Anti-Rh antibody molecules appeared to be similar to myeloma molecules in these respects. A few myeloma proteins and anti-Rh antibodies were encountered which reacted with some but not other anti-Gm(b) or anti-Gm(f) reagents; the only available Vi type myeloma protein from a Negro, specifically lacked the Gm(b3) factor.
The observations might be explained by the following hypothesis: In Caucasians with the common Gmf Gmb gene complex the Gm(b) antigenic determinants, except (b2), co-occur in certain molecules, which contain a polypeptide chain determined by the Gmb gene; the Gm(f) and (b2) determinants co-occur in other molecules, which contain a polypeptide chain determined by the Gmf gene. Individuals that lack some Gm(b) or Gm(f) determinants most likely have a gene partly different from Gmb or Gmf.
The value of studies with myeloma proteins from individuals of different racial groups was apparent from this study. One myeloma protein from a Chinese was unique in that it was both Gm(a+) and Gm(f+).