bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
QUANTITATIVE STUDIES ON THE BEHAVIOR OF SENSITIZED LYMPHOCYTES IN VITRO
Authors: Wilson Darcy B.
Published: June 2004

The cytocidal effect of specifically sensitized lymphoid cells on homologous target cells in culture can be inhibited by small quantities of an imidazole derivative of 6-mercaptopurine (imuran). This inhibition takes place only in the continuous presence of this drug, and at concentrations which apparently do not affect the viability of the attacking lymphoid cells. These results seem to support the contention that RNA-dependent protein synthesis on the part of the lymphoid cells is necessary for a destructive interaction between sensitized node cells and homologous target cells in vitro.
FORMATION OF CHARCOT-LEYDEN CRYSTALS IN HUMAN EOSINOPHILS AND BASOPHILS AND STUDY OF THE COMPOSITION OF ISOLATED CRYSTALS
Authors: Archer Gordon T. , Blackwood Angela
Published: June 2004

Methods are described for the isolation of human eosinophils and basophils from donor blood. Using these cell preparations Charcot-Leyden crystals were found to originate from both eosinophils and basophils when the cells were suspended in hypotonic saline solution. The crystals formed also when saline extracts of eosinophils and basophils were concentrated by ultrafiltration through dialysis tubing. Fractions of eosinophils were prepared and the crystals were obtained from the cytoplasmic fraction but not from the nuclear or granular fractions. Chemical studies showed the crystals to be protein in nature and some evidence is presented which suggests that RNA may decrease the tendency for the protein to crystallize out of solution.
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 (>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.
GENETIC CONTROL OF THE ANTIBODY RESPONSE
Authors: McDevitt Hugh O. , Sela Michael
Published: June 2004

Immunization of CBA and C57 mice with a branched, multichain synthetic polypeptide, poly (tyr,glu)-poly DL-ala--poly lys, ((T,G)-A--L), in Freund's complete adjuvant results in a tenfold or more difference in the antigen-binding capacity of sera from the two strains, although they respond equally to bovine serum albumin. Immunization of CBA x C57 F1, F1 x CBA, and F1 x C57 mice reveals definite genetic control of the response to (T,G)-A--L, which appears to be due to a single major genetic factor, with perhaps one or more modifying factors. Immunization of CBA and C57 mice with (H,G)-A--L, a synthetic polypeptide in which histidine replaces tyrosine, gives the opposite result, CBA's respond and C57's do not. From this, it appears that the genetic control of the response to (T,G)-A--L is specific for the antigenic determinant. The implications of these results are discussed.
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.
ANTIGENICITY OF POLYPEPTIDES (POLY ALPHA AMINO ACIDS)
Authors: Pinchuck Paul , Maurer Paul H.
Published: June 2004

The ability of mice to form antibodies against the random terpolymer glu57lys38ala5 is controlled by a codominant Mendelian factor. Three of 7 inbred strains were 100 per cent responders; the others were completely negative. All of these strains could make antibody to related polymers with higher alanine content (10 and 40 mole per cent). Breeding studies using the progeny of Swiss mice indicated that a similar genetic factor was involved.
FUNCTION OF THE RETICULOENDOTHELIAL SYSTEM
Authors: Normann Sigurd J. , Benditt Earl P.
Published: June 2004

The inhibitory effect of heat-aggregated albumin on carbon clearance has been studied with respect to the dose-dependent relationships involved. It has been found that the dose of aggregated albumin does not affect the degree of inhibition but does affect the duration of inhibition. Above a critical dose the duration increases exponentially with increasing albumin dose. The addition of gelatin to the carbon suspension was found to produce two effects: (a) it prolonged the inhibitory effect of a given aggregated albumin dose, and (b) it produced a slowing in the rate of carbon removal. The fact that foreign red cells inhibit carbon clearance in a manner similar to denatured albumin suggests that the relationships observed relative to denatured albumin may be generally applicable to carbon clearance and indeed may have application to phagocytic particles other than carbon.
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+).
PRODUCTION OF RUNT DISEASE IN TOLERANT MICE BY THE INJECTION OF SYNGENEIC LYMPHOID CELLS
Authors: Hilgard Henry R. , Martinez Carlos , Good Robert A.
Published: June 2004

When chimeric A strain mice tolerant of (A x C57BL/1)F1 hybrid skin grafts are injected with spleen cells from normal A donors the recipients develop weight loss, clinical evidence of runting, and death in some animals. Similar recipients injected with spleen cells from A strain donors immunized against C57BL/1 tissue show a more rapid onset of the runting process and increased mortality. Runting in. these experiments therefore results from an immune attack by the injected A strain lymphoid cells against the (A x C57BL/1)F1 hybrid tissue harbored by the chimeric recipients. Since the hybrid tissues of the chimeric recipients were derived from spleen cell populations we conclude that the immunologic rejection of lymphoid and hematopoietic tissue is sufficient to cause the runting syndrome.

C3H mice tolerant of A strain skin grafts because of the prior injection of viable or disrupted A strain spleen material were given 400 r of x-irradiation and an injection of C3H spleen cells. Only the chimeric C3H mice harboring viable A strain cells developed weight loss and clinical evidence of disease, showing again that runting occurs only when an attack can be made against viable lymphoid and hematopoietic tissue.

Normal A strain mice injected intravenously with 850 million (A x C57BL/1)F1 hybrid spleen cells reject hybrid skin grafts and do not develop runting, whereas the rejection of similar hybrid tissue present in chimeric A strain mice results in runting. It is concluded that runting will occur only when the immunologic attack is directed against lymphoid and hematopoietic tissue which has become established within host tissues. The possibility that runting may result from hypersensitivity reactions occurring in the lymphoid tissues is discussed.
ENHANCED RESISTANCE TO STREPTOCOCCAL INFECTION INDUCED IN MICE BY CELL WALL MUCOPEPTIDE
Authors: Rotta Jiri , Prendergast Thomas J. , Karakawa Walter W. , Harmon Charles K. , Krause Richard M.
Published: June 2004

The streptococcal cell wall mucopeptide when injected into mice either intraperitoneally or intravenously enhances the resitance to subsequent challenge with virulent Group A streptococci. Rabbits which are injected intravenously with solubilized mucopeptide develop a fever response which has a resemblance to that achieved with endotoxin.

Mice which survive 6 to 7 weeks after challenge with virulent Group A streptococci yield at autopsy search Group A streptococci serologically identical to the challenge organisms. A preparative dose of cell walls injected into mice prior to challenge diminished this late recovery of streptococci.

Group A-variant streptococci were recovered from mice which survived challenge and carried the organisms for several weeks. Filterable bacterial forms, which grew on L form media, were recovered from infected mice. The serologic type of the L forms was identical to that of the challenge organisms.
COLICINE K
Authors: Goebel Walther F. , Staub Anne Marie
Published: June 2004

1. The immunization of horses with the colicinogenic bacillus E. coli K235 L + O(m) stimulates antibodies which precipitate and neutralize colicine K and neutralize the heterologous colicine I as well.

2. Unlike rabbits, horses evoke predpitating antibodies for the sialic acid-containing polysaccharide colominic acid.
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Sell Stewart , Gell P. G. H.
Published: June 2004

Lymphocytes from the peripheral blood of newborn rabbits heterozygous for IgG allotypes As4 and As5, or As5 and As6, obtained at an age when only the maternal allotypic determinants are detectable in the serum, may be stimulated in vitro to transform into "blast" cells with antiallotype sera directed against the determinants contolled both by the maternal and by the paternal chromosomes. This result rules out the possibility that allotypic specificity is conferred upon lymphocytes by environmental IgG and suggests that the lymphocytes of newborn rabbits have the potential to synthesize IgG determinants either in the form of intact IgG molecules or constituent polypeptide chains.
STUDIES OF ADENOVIRUS SV40 HYBRID VIRUSES
Authors: Rowe Wallace P. , Baum Stephen G.
Published: June 2004

E46+ virus purified by limiting dilution and plaque isolation in AGMK cells consists of a mixture of hybrid and non-hybrid virus particles. Of 102 plaque isolates obtained in HEK cells, 98 contained no detectable hybrid virus, while 4 contained a small proportion of hybrid virus. Plaque isolates from AGMK cells uniformly induced SV40 neoantigen, but when these plaque isolates were plaqued in HEK cells the progeny were again non-hybrid adenovirus. It thus appears impossible to obtain a pure line of hybrid virus.

The proportion of hybrid virus produced in HEK cells fell progressively with decreasing multiplicity of infection, and plaque induction by E46+ virus in AGMK followed 2-hit kinetics, indicating that the hybrid virus particles are defective and require dual infection with non-hybrid virus for their propagation.
STUDIES ON THE MECHANISM OF ACTION OF RILEY VIRUS
Authors: Rowson K. E. K. , Mahy B. W. J. , Salaman M. H.
Published: June 2004

The level of viraemia was determined in serial blood samples obtained from 2 mice after the injection of Riley virus. The plasma virus titre rose rapidly to a peak value of 109 to 1010 ID50 per ml by 24 hours after infection, and then fell slowly to a level of 105 to 106ID50 per ml by the 10th day after infection, where it remained relatively stable.

Neither blockade of the RES with thorotrast, zymosan, or carbon, nor stimulation of the RES with stilboestrol or zymosan, before the injection of Riley virus, produced any observable alteration in the level of viraemia attained 24 hours after infection. However 10 days or more after infection with Riley virus blockade of the RES with thorotrast caused a transitory rise, and stimulation of the RES with stilboestrol caused a slight but prolonged fall, in the level of viraemia. Zymosan injection at this period of infection caused an initial rise, followed by a fall, in the level of viraemia; these changes correlated with the initial period of blockade and the subsequent period of stimulation of the RES observed in carbon clearance studies.

The clearance of injected Riley virus particles from the plasma over a period of 3 hours after injection was measured in previously uninfected mice and mice which had been infected with Riley virus for 3 weeks. The mice which had been infected 3 weeks before the test cleared rather more of the injected virus than the previously uninfected mice.

It is concluded that although the activity of the RES affects, and may determine, the level of viraemia, the permanence of the viraemia in Riley virus-infected mice does not appear to be due to a failure of the RES to clear virus particles from the plasma.
VASCULAR RESPONSE IN THE ISOLATED RAT LIVER
Authors: Nolan James P. , O'Connell Cornelius J.
Published: June 2004

Sublethal doses of E. coli endotoxin were shown to cause direct slowing of blood flow in the isolated perfused rat liver. Concentrations as low as SO ng per ml elicited this vasoconstrictive response. The decrease in flow after the initial lipopolysaccharide injection was immediate and lasted from. 5 to 15 minutes before recovering to baseline values. Succeeding injections of the same concentration, however, had little or no circulatory effects, and this tachyphylaxis persisted through 5 hours of perfusion. The replacement of the perfusate with fresh whole blood after several hours partially restored the ability of the hepatic vasculature to respond to the lipopolysaccharide. However, the presence of plasma or formed blood elements was not essential to the response, as brisk decreases occurred after endotoxin when a modified Ringer's solution was the sole perfusate. Catecholamines or serotonin did not appear to be key mediators in the primary vascular effect of endotoxin as phentolamine and methysergide administration did not appreciably modify the response. On the other hand, hydrocortisone when given in large doses with the endotoxin or in smaller doses 15 to 45 minutes prior to the lipopolysaccharide completely blocked vasoconstriction. The isolated preparation seems to be an excellent model for the study of direct circulatory effects of various substances in the liver.
IMMUNOLOGICAL STUDIES IN ULCERATIVE COLITIS
Authors: Hammarström Sten , Lagercrantz Rutger , Perlmann Peter , Gustafsson Bengt E.
Published: June 2004

Sera from patients with ulcerative colitis contain antibodies which hemagglutinate sheep red cells, sensitized with phenol-water extracts from. colon, cecum, or feces of germfree rats. Minor concentrations of such antibodies are also present in a certain fraction of normal human sera. Hemagglutination and hemagglutination inhibition experiments with human erythrocytes and with the rat extracts showed that the latter contained an antigen similar to human blood group A antigen. In contrast, a blood group B-like antigen could not be detected in these extracts. However, experiments with eel serum indicated that these extracts also contained an antigen similar to the H antigen of the human ABO system.

Absorption of ulcerative colitis sera with human A1 erythrocytes but not that with B or O erythrocytes gave, in a few cases, a slight reduction of the hemagglutinating titers against rat cecum-sensitized sheep erythrocytes. In contrast, this treatment considerably reduced such titers when found in sera from healthy persons or from patients with unrelated diseases. It could be concluded that the rat extracts also contained a "colon" antigen, detected with antibodies, present at elevated titers, in the sera of ulcerative colitis patients, but not in those of the controls. This colon antigen is immunologically distinct from the blood group antigens studied.

Hemagglutination inhibition experiments indicated that A, H and colon antigen were widely distributed throughout the gastrointestinal tract of the germfree rats. The colon antigen was found to be enriched in the extracts from colon, cecum, and feces. Fluorescent antibody staining provided evidence that both the colon antigen and the A antigen were present in similar sites of the colon and cecum mucosa, particularly in goblet cells of the crypts, and in the mucus.
GM AND INV FACTORS IN SUBCLASSES OF HUMAN IGG
Authors: Terry William D. , Fahey John L. , Steinberg Arthur G.
Published: June 2004

Human G myeloma (7S γ2-myeloma) proteins were investigated for relationships between Gm and Inv genetic factors and the different antigenic types of heavy polypeptide chains (γ-chains) and light polypeptide chains.

Myeloma proteins were isolated from the sera of 1 Chinese, 60 white and 28 Negro individuals. These 89 proteins were tested for eight Gm factors [Gm(a), Gm(x), Gm(b2), Gm(f), Gm(b1), Gm(b3), Gm(b4), and Gm(c)], and two Inv factors [Inv(l) and Inv(b)]. Results of the tests were correlated with the four γ-chain subclasses (γ2a, γ2b, γ2c and γ2d) and the two types of light polypeptide chains, κ-chains (type K or I) and λ-chains (type L or II) found in human IgG molecules.

1. Gm factors were limited to myeloma proteins with heavy polypeptide chains of the γ2b- and γ2c-subclasses. No Gm factors were detected on γ2a- and γ2d-myeloma proteins or on a "heavy-chain" disease protein of subclass γ2d.

2. γ2b-Proteins were positive for at least one Gm factor and were either Gm(a+), Gm(a + x+), or Gm(b2+ f+).

3. γ2c-Myeloma proteins, and one γ2c-"heavy-chain" disease protein, were positive for at least one Gm factor and contained various combinations of factors Gm(b1), (b2), (b4), and (c). Myeloma proteins from 3 Negroes were included in this group.

4. Inv factors (l) and (b) were limited to myeloma proteins with κ-light polypeptide chains. These Inv factors were not detected on proteins with λ-light polypeptide chains.

5. Most (70 per cent) of the γ2b- and γ2c-proteins with κ-chains were Inv(l+) or Inv(b+). None of the γ2a- or γ2d-proteins with κ-chains, however, contained these Inv factors.
ROLE OF THE THYMUS IN TOLERANCE
Authors: Isaković Katarina , Smith Stanley B. , Waksman Byron H.
Published: June 2004

Rats thymectomized and irradiated as adults were restored to immunologic reactivity by grafts of normal adult rat thymus and bone marrow. Reactivity of the delayed (cellular) type and formation of mercaptoethanol-sensitive (MES) and mercaptoethanol-resistant (MER) antibody returned within 3 weeks, while Arthus reactivity remained subnormal till 9 weeks after irradiation and grafting. When the thymus donor was tolerant to BGG, the recipient showed specific non-reactivity to this antigen 3 weeks and, to a much lesser extent, 6 weeks after grafting. This non-reactivity affected delayed responses and MER antibody. No effect was noted on Arthus reactivity and a slight effect on MES antibody. Controls showed that the non-reactivity was not due to transfer of free antigen at the time of grafting. It was concluded that different source organs are responsible for different immune functions and that specific immunologic tolerance may be induced within such an organ as the thymus.
STUDIES OF A MYXOVIRUS RECOVERED FROM PATIENTS WITH INFECTIOUS HEPATITIS
Authors: Liebhaber Harvey , Krugman Saul , McGregor Dorothy , Giles Joan P.
Published: June 2004

A virus has been isolated from the serum and urine of patients with infectious hepatitis. This virus is a member of the parinfluenza group. It is serologically distinct from the known members of the group, but apparently is antigenically related to the simian type-2 parainfluenza viruses.

A causal relationship between WB virus and infectious hepatitis has not been established.
STUDIES OF A MYXOVIRUS RECOVERED FROM PATIENTS WITH INFECTIOUS HEPATITIS
Authors: Prose Philip H. , Balk Samuel D. , Liebhaber Harvey , Krugman Saul
Published: June 2004

WB virus has been shown to have a fine structure which is characteristic of members of the mumps-NDV-parainfluenza group of viruses.

Viral internal component has been demonstrated within the cytoplasm of infected cells. The incorporation of internal component into virus filaments at the cell surface has also been demonstrated. The evidence presented suggests that virus filament formation occurs by a process of invagination of the cell membrane about the coiled strands of internal component lying beneath the membrane.
STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES
Authors: McCarty Maclyn , Avery Oswald T.
Published: June 2004

It has been shown that extremely minute amounts of purified preparations of desoxyribonuclease are capable of bringing about the complete and irreversible inactivation of the transforming substance of Pneumococcus Type III. The significance of the effect of the enzyme, and its bearing on the chemical nature of the transforming substance, together with certain considerations concerning the biological specificity of desoxyribonucleic acids in general, are discussed.
STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES
Authors: McCarty Maclyn , Avery Oswald T.
Published: June 2004

1. An improved method is outlined for the isolation and purification of the pneumococcal transforming substance. This method makes use of the fact that citrate inhibits the destructive action of the enzyme, desoxyribonuclease, which is released together with the active material during lysis of the living bacterial cells. A fivefold greater yield of purified transforming agent is obtained by the present method than by the procedure previousiy described.

2. The specific transforming substance has been isolated from pneumococci of types II and VI, in addition to Type III. In each instance the biologically active material has been found to consist of desoxyribonucleic acid.
STUDIES ON THE COMPLEMENT FIXATION ANTIGENS OF INFLUENZA VIRUSES TYPES A AND B
Authors: Wiener Maria , Henle Werner , Henle Gertrude
Published: June 2004

Two types of specific particles can be obtained from allantoic fluid preparations of influenza A and B virus. The larger particle which possesses all the attributes of the virus and which shows a sedimentation constant of about 600 S was compared with the smaller component (30 S) by complement fixation technic.

The 30 S component can be differentiated from the 600 S particle by the patterns of the optimal antigen-antibody relationships and by cross-absorption of the sera with the two particles.

Some of the 30 S-type antigen can be demonstrated in higher concentrations of the 600 S particles by the use of sera containing only anti-30 S; i.e., sera carefully absorbed with 600 S component. Also, upon sonic vibration of the 600 S particle, serologically active material was released which behaved in every respect like the 30 S antigen.

The response of human beings to these antigens was found to vary. Antibodies to the 30 S component developed in the majority of subjects exposed to active virus either under epidemic or experimental conditions, but only rarely following vaccination with three different vaccines.

In selecting sera without 30 S antibodies a fairly close correlation between the antibody titers obtained by inhibition of hemagglutination and complement fixation with the 600 S component was obtained. The presence of 30 S antibodies prevented such a correlation.

The reaction with the 30 S antigen may be of value in the diagnosis and study of the epidemiology of influenza.
PRECIPITIN REACTIONS OF HIGHLY PURIFIED INFLUENZA VIRUSES AND RELATED MATERIALS
Authors: Knight C. A.
Published: June 2004

Antisera to purified PR8 virus, to purified protein from normal allantoic fluid, and to purified normal mouse lung particles were obtained from hyper-immunized rabbits and used in quantitative precipitin tests employing various purified preparations of influenza virus and related materials as antigens. The results of those tests indicated that the most highly purified preparations of PR8 or of Lee influenza virus obtained from infectious allantoic fluid contain an antigen characteristic of normal allantoic fluid and likewise that highly purified mouse lung PR8 virus contains an antigen characteristic of normal mouse lungs. Since the infectivity of virus preparations which were ultracentrifugally and electrochemically homogeneous was precipitated by the appropriate antisera to normal antigens, it was concluded that the normal antigens constitute a part of the 100 mµ particles with which influenza virus activity is at present deemed to be associated. It was estimated from quantitative precipitin data that the most highly purified preparations of PR8 and of Lee influenza viruses obtained from infectious allantoic fluid contain at least about 20 and 30 per cent, respectively, of an antigenic structure characteristic of the sedimentable protein of normal allantoic fluid.
PERIOD OF INFECTIVITY OF PATIENTS WITH HOMOLOGOUS SERUM JAUNDICE AND ROUTES OF INFECTION IN THIS DISEASE
Authors: Havens W. Paul
Published: June 2004

1. Pooled specimens of serum obtained from 3 human volunteers three-fourths through their respective 56, 66, and 70 day incubation periods of homologous serum jaundice produced the disease in 1 out of 4 human volunteers following parenteral inoculation.

2. Serum specimens obtained from these same 3 patients during the acute, pre-icteric phase of their homologous serum jaundice produced the disease in 3 out of 4 human volunteers following parenteral inoculation.

3. These same sera, proven to be infectious by parenteral inoculation, failed to produce disease when ingested by 10 other human volunteers.

4. Pooled specimens of serum obtained in the convalescent phase (28 to 32 days after onset) of these 3 patients failed to produce apparent infection when inoculated parenterally into 5 human volunteers.

5. Pooled specimens of feces of 3 patients obtained in the acute phase of homologous serum jaundice, when virus was proven to be in the serum, were not demonstrably infectious when fed to 6 volunteers.

6. These findings are slightly different from those encountered in a similar study with infectious material from cases of infectious hepatitis.
TYPE-SPECIFIC PROTECTION AND IMMUNITY FOLLOWING INTRANASAL INOCULATION OF MONKEYS WITH GROUP A HEMOLYTIC STREPTOCOCCI
Authors: Watson Robert F. , Rothbard Sidney , Swift Homer F. ,   With the Technical Assistance of Gilbert de Mello
Published: June 2004

1. Nasopharyngeal carrier states of several weeks to several months duration were induced in the Macaca mulatta by the intranasal inoculation with matt strains of group A streptococci.

2. Following such a successful inoculation with a particular type of group A streptococcus, the animal was usually resistant to reimplantation with that same type for several months to a year or more, although reimplantation with a heterologous type could generally be easily effected.

3. This resistance was shown to be closely correlated with the antibodies directed toward the type-specific M antigen, not toward the T antigen of the strains employed.

4. A majority (83.8 per cent) of the animals in which intranasal inoculation was followed by successful implantation developed significant increases in the antistreptolysin O titres of their sera; and in a limited number of instances, type-specific agglutinins and bacteriostatic antibodies were demonstrable in the animals' sera following successful implantation.

5. Nasopharyngeal carrier states could not be induced with the glossy, avirulent variants of group A streptococci; these animals, moreover, failed to show antibody responses and were susceptible to implantation with the matt variants of the homologous glossy strains.

6. The findings are in accord with the known facts regarding immunity to group A streptococci gained through experiments on rodents; and the possible relationship of these observations to the problem of type-specific immunity in human beings is discussed.