bluuebunny/crossref_metadata_2025_split huggingface dataset:
Murine syngeneic mixed lymphocyte response. I. Target antigens are self Ia molecules
Authors: Glimcher LH , Longo DL , Green I , Schwartz RH 
Published: June 2004

A system has been described that produces a murine syngeneic mixed lymphocyte response (MLR) comparable in magnitude to an allogeneic MLR. The responder cells in these cultures exhibit the classic immunologic characteristics of both memory and specificity. Studies using radiation-induced bone marrow chimeras of F(1) {arrow} parent type indicated that, similar to many other T cell-mediated immune responses, the response of the T lymphocytes in the syngeneic MLR was major histocompatibility complex-restricted and was determined by the environment in which the T cells matured. Using responder T cells from F(1) {arrow} parent chimeras and stimulator cells from H-2 recombinant strains, it was possible to map the genes involved in the stimulation to the K and/or I regions. In addition, blocking studies with monoclonal anti-Ia antibodies suggested that in the B10.A strain the critical molecules were products of both the I-A(k) and I-E(k) subregions.
The issue of whether the syngeneic MLR is directed solely at self I-region antigens or whether the response represents proliferation to an unknown antigen in association with self I-region determinants was also addressed. Secondary syngeneic MLR were successfully performed in normal mouse serum and with stimulator cells prepared in the absence of bovine serum albumin to rule out the possibility that xenogeneic serum antigens were involved in the stimulation. The possibility that the syngeneic MLR might represent a secondary response to environmental antigens was eliminated by using germ- free mice as a source of stimulator cells and by demonstrating that spleen cells from unimmunized, fully allogeneic chimeras (B10.A {arrow} B10) could generate a normal syngeneic MLR even though such chimeras could not be primed to respond to any foreign antigens unless supplemented in vivo with a source of antigen-presenting cells syngeneic to the B10 host. The possibility that the syngeneic MLR was a primary response to a foreign antigen was considered unlikely because by using our culture conditions we could not obtain a primary antigen response or a secondary antigen response after in vitro priming to a variety of potent foreign antigens. Finally, the possibility that the syngeneic MLR represents a response to a variety of minor histocompatibility self antigens in association with self Ia molecules was eliminated by showing that the secondary responses to H-2 compatible, non-H-2 different strain (A/J vs. B10.A and C3H, or BALB/c vs. B10.D2 and DBA/2) were comparable to the secondary responses to syngeneic stimulators. Thus, we conclude that the target antigens in the syngeneic MLR are solely determinants on self Ia molecules, although the functionally equivalent possibility of a single, nonpolymorphic, minor self antigen seen in association with self Ia molecules cannot be excluded.
A specific biosynthetic marker for immature thymic lymphoblasts. Active synthesis of thymus-leukemia antigen restricted to proliferating cells
Authors: Rothenberg E 
Published: June 2004

Large cortical thymocytes from C57BL/6-Tla(a) mice have been prepared rapidly and in high yield by a combination of centrifugal elutriation and differential binding to peanut agglutinin (PNA)-coated plates. The cells in these lymphoblast-rich fractions were clearly distinct from the majority of thymocytes, with up to 70 percent in the S or G(2) + M phases of the cell cycle and an average rate of [(35)S]methionine incorporation per cell up to 20 times higher than that of the majority population.
The populations of cells resolved in this fractionation were characterized by monitoring their rates of synthesis of specific glycoproteins, thymus- leukemia antigen (TL) and the Lyt-2, Lyt-3 complex (Lyt-2/3), relative to their total protein synthesis. Cells that bound to PNA synthesized high levels of Lyt-2/3, consistent with their identification as cortical thymocytes. Those that failed to bind made little or no Lyt-2/3, as expected for medullary cells, The fraction of dividing lymphoblasts that bound to PNA was enriched in cortical thymocyte precursors, including all the large cells detectably active in synthesizing Lyt-2. It differed sharply from the small cortical cells, however, in the synthesis of TL. Although both populations displayed abundant surface TL, the TL glycoprotein was produced actively in fractions containing dividing cells but made at a drastically reduced rate by the nondividing majority of cortical thymocytes. Thus, TL seems to be made at a narrowly circumscribed stage of early thymocyte development that is correlated with rapid proliferation. In most of the descendants of such blast cells, the TL glycoprotein is presumably retained on the cell surface as long as no substantial membrane turnover takes place. Ongoing TL synthesis may therefore serve as a marker for a unique developmental state which terminates rapidly in normal differentiation but may be extended by agents that give rise to TL(+) thymic lymphomas.
Human dendritic cells. Enrichment and characterization from peripheral blood
Authors: Van Voorhis WC , Hair LS , Steinman RM , Kaplan G 
Published: June 2004

Previous studies demonstrated that lymphoid tissues of mice and rats contain small numbers (less than 1 percent of nucleated cells) of dendritic cells (DC) with special cytologic, surface, and functional properties. We show here that similar DC represent 0.1-0.5 percent of human peripheral blood mononuclear cells. DC can be enriched to 20-60 percent purity by a multistep procedure analogous to that used in mice. Adherent peripheral blood mononuclear cells are cultured overnight, and the released cells are depleted of monocytes and B cells by readherence to plastic, rosetting with erythrocytes coated with anti-human IgG, and centrifugation in dense albumin columns. Enriched DC have similar cytologic features to rodent DC by light and electron microscopy.
DC express HLA, and HLA-DR and the leukocyte-common antigens. They lack phagocytic capacity, receptors for antibody-coated and neuraminidase-treated erythrocytes, surface and intracellular Ig, esterase, peroxidase, and azurophilic granules. DC do not react with several monoclonal antibodies directed to phagocytes (OKM 1, "mac-1," 63D3, and 61D3) and T cells (OKT 3, 6, 8). Unlike the mouse, human DC express complement receptors. When maintained in culture for 4 d, human DC did not give rise to either B cells or monocytes. Therefore, DC identified by cytologic criteria are distinct from other leukocytes.
Enriched populations of DC have been compared to fractions enriched in monocytes, B cells, and T cells in three functional assays: stimulation of the primary allogeneic mixed leukocyte reaction, stimulation of the primary syngeneic MLR, and accessory function for the proliferation of periodate- modified T cells. In each case, the DC fraction was 10-fold or more active than other cell fractions. We conclude that DC circulate in man, and represent the principal cell type required for the initiation of several immune responses.
Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice
Authors: Steinman RM , Gutchinov B , Witmer MD , Nussenzweig MC 
Published: June 2004

Clone 33D1 is a mouse-rat hybridoma that secretes a specific anti-dendritic cell (DC) monoclonal antibody (14). Because the antibody kills DC in the presence of rabbit complement, it can be used to study the functional consequences of selective DC depletion. Previous data on the cell specificity of 33D1 were first extended. By cytotoxicity (rabbit complement) and indirect immunofluorescence (biotin-avidin technique), 33D1 reacted with DC but not with macrophages nor other splenocytes. In contrast, the monoclonal antibody, F4/80 (15), reacted with macrophages but not DC.
The functional assay evaluated in this paper was stimulation of the primary mixed leukocyte reaction (MLR). 33D1 antibody itself did not inhibit stimulation by enriched populations of DC. In the presence of complement, 33D1 killed DC and ablated stimulatory function.
The effect of 33D1 and complement on MLR stimulation by heterogenous cell mixtures was then evaluated. Removal of DC from unfractionated spleen suspensions reduced stimulatory capacity 75-90 percent, comparable to that produced with specific anti-Ia antibody and complement. Stimulation of both proliferative and cytotoxic responses was reduced. DC depletion had similar effects on MLR generated across full strain differences, or across selected subregions (H2I, H-2K/D) of the major histocompatibility complex.
To further compare the functional properties of spleen DC and macrophages, MLR stimulation by adherent and nonadherent fractions of spleen were tested separately. 62 +/- 8 percent of the total stimulatory capacity of spleen was in the plastic adherent population. Activity was ablated greater than 90 percent after elimination of DC. MLR stimulation by 24-h cultures of spleen adherent cells, which contained a three- to sixfold excess of Ia(+) macrophages, was also ablated when DC were removed. Stimulation by nonadherent spleen was more resistant, but was reduced 50-75 percent by 33D1 and complement.
The function of spleen cells treated with 33D1 or anti-Ia antibody and complement was restored with a small inoculum of purified DC. The latter corresponded to 0.5 percent of total stimulator cells and were enriched by previously described techniques that did not require the 33D1 antibody.
We conclude that the DC, a trace component of mouse spleen, is the principal cell type required for stimulation of the primary MLR. Because other cells are not immunogenic, but do express Ia and H-2 alloantigens, DC likely represent the critical accessory cell required for the induction of lymphocyte responses.
PERIOD OF INFECTIVITY OF PATIENTS WITH EXPERIMENTALLY INDUCED INFECTIOUS HEPATITIS
Authors: Havens Walter P. 
Published: June 2004

1. Serum and stools obtained in the pre-icteric phase of one patient, and pooled specimens of the same materials from 5 patients with experimentally induced (by feeding) infectious hepatitis produced the disease in 10 out of 15 human volunteers following feeding or parenteral inoculation.
2. Pooled specimens of urine and nasopharyngeal washings from 5 patients, obtained in the acute phase of infectious hepatitis when virus was proven to be in the stool and serum, were not demonstrably infectious when fed and given intranasally to 6 volunteers.
3. Serum obtained in the midincubation period of one patient with experimentally induced infectious hepatitis failed to produce apparent infection when inoculated parenterally into 3 human volunteers. This is in contrast to the situation in homologous serum jaundice in which "virus" has been demonstrated in the sera of volunteers during the incubation period.
4. Serum and stools obtained from one patient and pooled specimens of stools from 5 patients 25 to 31 days after onset of experimental infectious hepatitis failed to produce apparent infection in 10 human volunteers.
5. No appreciable difference was detected in length of incubation period following the parenteral administration of widely different amounts of the same strain of "virus."
THE ABSENCE OF ANTIBODY IN THE MACROPHAGES DURING MAXIMUM ANTIBODY FORMATION
Authors: Ehrich W. E. , Harris T. N. , Mertens E. 
Published: June 2004

Following the injection of dysentery antigen in saline or in saline-in-paraffin-oil emulsion into the pad of the rabbit's hind foot, considerable quantities of antibody were recovered from the popliteal lymph node, while the tissue at the site of injection, containing many granulocytes and numerous macrophages, revealed only insignificant quantities of antibody.
Following the injection of various dysentery and typhoid antigen combinations into the abdominal cavity, no antibody was found in the isolated granulocytes and macrophages of the peritoneal exudate, while the supernatant fluid revealed titers that roughly paralleled those of the blood serum. Similar results were obtained when animals were injected first with antibody intravenously, and subsequently with an unspecific irritant intraperitoneally. The presence of antibody in the supernatant fluid was, therefore, interpreted as being due to secondary concentration (fixation) in an inflamed area.
These findings together with the previously described observations on the lymphocyte seem to show that the macrophage does not synthesize agglutinins against dysentery or typhoid bacilli.
THE SITE OF ANGIOTONIN DESTRUCTION
Authors: Sapirstein Leo A. , Reed Racheal K. , Page Ernest W. 
Published: June 2004

1. Theoretical considerations render it unlikely that the greatest part of the angiotonase found in the organism is available for the destruction of angiotonia. A priori considerations support the view that only plasma angiotonase is involved in angiotonin destruction in vivo.
2. We have utilized the magnitude and duration of the presser response to angiotonin as an index of available angiotonase, and we have found that: (a) Nephrectomy and evisceration are without marked effect on angiotonin response. (b) Hemorrhage and hemodilution without shock cause a striking increase in the response to angiotonin and this appears to be due to removal of the plasma rather than the cells. Shock developing after hemorrhage results in a state of refractoriness to angiotonin. (c) Intact red cells in vitro have no destructive action on angiotonin, but after hemolysis they have several hundred times the activity of plasma, (d) Intravascular hemolysis, whether produced in vitro or in vivo, decreases the response to angiotonin to a degree which is consistent with the hypothesis that the normal animal destroys angiotonin entirely in its plasma. The active principle in hemolyzed blood is destroyed by heating to 65–70°C. for 15 minutes.
3. These findings support the hypothesis that all or at least the greatest part of angiotonin destruction under physiological circumstances occurs in the plasma, and the significance of this hypothesis is discussed.
IMMUNOCHEMICAL STUDIES ON BLOOD GROUPS
Authors: Bendich Aaron , Kabat Elvin A. , Bezer Ada E. ,   With an Appendix by Erwin Brand, Ph.D., and Leo J. Saidel
Published: June 2004

1. Studies on a number of individual hog stomachs have shown that substances with blood group A activity cannot be obtained from all hogs. Of ten stomachs studied, only seven yielded products with blood group A activity. All ten purified preparations, however, showed identical properties with respect to nitrogen, reducing sugar, glucosamine, acetyl, and relative viscosity. Six of the seven active samples were of equal potency in precipitating anti-A; the seventh was slightly less active.
2. Preparations from random pools of hog stomachs, although possessing the same analytical properties, were of lower activity than those from individual active stomachs as determined by the microquantitative precipitin method.
3. An immunochemical method for estimating the absolute purity of the blood group A substance by determining the proportion of its glucosamine precipitated by excess anti-A was developed. Values of about 84 per cent for the purity of six of the seven purified active preparations from the individual hog stomachs were obtained.
4. The inactive products, unlike the active ones, did not stimulate the production of anti-A on injection into human beings and did not precipitate anti-A or inhibit hemagglutination of A erythrocytes by anti-A.
THE PREPARATION OF SECTIONS OF GUINEA PIG LIVER FOR ELECTRON MICROSCOPY
Authors: Claude Albert , Fullam Ernest F. 
Published: June 2004

1. A method is described whereby sections of guinea pig liver cells can be prepared for electron microscopy after fixation.
2. The high resolving powerof the electron microscope reveals the presence of two components, one particulate, the other apparently of fibrous texture, in the ground substance of the cells.
MOBILIZATION OF BASOPHILE SUBSTANCE (RIBONUCLEIC ACID) IN THE CYTOPLASM OF LIVER CELLS WITH THE PRODUCTION OF TUMORS BY BUTTER YELLOW
Authors: Opie Eugene L. 
Published: June 2004

Butter yellow (dimethylaminoazobenzene) causes degenerative changes in liver cells accompanied by chromatolysis of cytoplasmic structures that stain with basic dyes because they contain ribonucleic acid. These changes are profoundly modified by the protein content of the diet.
Chromatolysis is succeeded by focal regeneration with reaccumulation of ribonucleic acid in the cytoplasm of liver cells; these foci of basophile hyperplasia have their origin in the parenchyma surrounding portal spaces and consist of cells arranged in columns or as tubules with lumina.
Hepatomas arise from foci of basophile hyperplasia and corresponding with the arrangement of cells in these foci may be trabecular or adenomatous.
Butter yellow causes new formation of bile ducts which arise chiefly in the immediate neighborhood of secondary portal spaces and produce the precancerous lesion, designated cholangiofibrosis. These bile ducts may accumulate ribonucleic acid in their cytoplasm and undergo hyperplasia.
Cholangiomas arise from newly formed bile ducts that are the site of basophile hyperplasia.
Changes accompanying chromatolysis and basophile hyperplasia aid in the definition of structural elements of the cytoplasm and in the localization of ribonucleic acid with relation to the mitochondria.
REACTIONS OF MONKEYS TO EXPERIMENTALLY INDUCED INFLUENZA VIRUS A INFECTION
Authors: Saslaw Samuel , Wilson H. E. , Doan Charles A. , Woolpert O. C. , Schwab J. L. 
Published: June 2004

1. Macaca mulatta monkeys on a normal diet have proved resistant to intranasal but not to intratracheal inoculation of influenza virus.
2. Neutralizing antibodies appeared 8 to 10 days after inoculation with either living or heat-inactivated virus. The antibodies were noted to be still present as long as 9 months after infection with living virus.
3. A specific granulopenic leucopenia characteristically followed primary influenza virus inoculation, regardless of altered conditions of diet, exposure, and route of inoculation, but it was not observed in monkeys previously infected with the same virus, all of which invariably survived.
4. Nutritional deficiency and exposure to cold increased the susceptibility of monkeys on intranasal instillation of the virus; the leucopenia was profound and fatalities frequently occurred even though neutralizing humoral antibodies developed as promptly and in relatively the same titer as under optimum nutritional conditions.
PREPARATION AND PROPERTIES OF SHIGA TOXIN AND TOXOID
Authors: Dubos René J. , Geiger James W. 
Published: June 2004

1. Shigella dysenteriae (Shiga) can, under the proper cultural conditions, produce a soluble toxin which is independent of the specific somatic polysaccharide antigen. A method is described for the rapid production of this toxin by an avirulent R variant of this organism.
2. The amount of bacterial protoplasm synthesized, and the yield of toxin produced, are very much increased when the culture is grown under conditions which favor aerobic metabolism and which do not permit accumulation of organic acids.
3. Although addition of an excess of inorganic iron to the medium does not interfere with the synthesis of bacterial protoplasm, maximal toxin production is obtained only in media which have been freed of the metal.
4. R Shiga bacilli grown under conditions of extreme aerobiosis at pH 7.0 in a simple medium free of inorganic iron and containing fumaric acid, glucose, meat extract, and peptone, give rise within 24 to 36 hours to cultures exhibiting a high degree of toxicity. The toxic principle rapidly becomes soluble as the cells die; it can be concentrated, purified, and freed of phosphorus by selective precipitation methods.
5. The toxin is fairly resistant to heat at pH 6.0 but rapidly denatured at pH 9.0. It is only slowly inactivated by trypsin. It filters readily and without loss of activity through anionic exchange resins but is precipitated and adsorbed by cationic resins which retain the nitrogen and toxic activity of the preparation.
6. The most active preparations of toxin available possess an LD50 of 1 to 10 µg. for mice and rabbits. Young mice (up to 5 weeks of age) are more resistant than older animals.
7. The soluble toxin can be detoxified by treatment with 0.5 per cent formalin at pH 8.5; detoxification does not take place at lower pH whereas treatment at higher pH destroys specific antigenicity. Mice immunized with Shiga toxoid (in solution, or in the form of an alum precipitate) develop active immunity to the toxin.
THE FATE OF INJECTED PARTICULATE ANTIGENS IN RELATION TO THE FORMATION OF ANTIBODIES
Authors: Harris T. N. , Ehrich W. E. 
Published: June 2004

Earlier studies have shown that the injection of antigenic material into the pad of the rabbit's foot is followed by the appearance of antibodies in the regional lymph node, in lymph coming from that node, and especially in the lymphocytes present in such efferent lymph. In the present work the fate of particulate antigenic material has been investigated during the period between its injection into the foot of the rabbit and the appearance of antibodies in the regional lymphatic tissue.
It has been found that soluble substance of the same immunologic specificity as the antigenic material injected can be identified in extracts of the injected tissue and of the regional lymph node, and in the efferent lymph from that node. The concentration of this soluble material falls off slowly in the injected tissue in the course of the few days following the injection. It falls off quickly in the extract of the lymph node and in the lymph itself, and its disappearance is succeeded by the appearance of antibody.
Evidence is presented that the immunologically active substance is derived from the injected antigenic material by a physiologic process, and this process is discussed as the means by which antigens, originally comprised in cells, are made available to the lymphocyte.
EFFECT OF IN VITRO CULTIVATION ON THE PATHOGENICITY OF WEST NILE VIRUS
Authors: Koprowski Hilary , Lennette Edwin H. 
Published: June 2004

The West Nile virus was cultivated in suspended cell culture media employing several different tissue components, and it has been observed to survive in culture for at least 32 days.
Continued propagation of the virus in vitro resulted in a change in its pathogenicity. The change lay in a marked reduction or a complete loss of the ability of the virus to produce fatal infections in mice and in hamsters on peripheral inoculation, although there was no obvious simultaneous alteration in the lethal effect of the virus by the cerebral route.
In mice, the extent to which invasiveness was lost depended upon the passage level of the virus and the age of the test animals. The younger (and more susceptible) the mice, the greater the number of passages which was required to diminish the virulence of the virus by peripheral routes; after 68 passages, the virus still retained its full capacity to kill 3-day-old mice, while its ability to kill 8-day-old mice was reduced and its ability to kill mice 14 or more days of age was essentially abolished. How soon the loss of pathogenicity occurs in hamsters has not been determined.
Prolonged cultivation rendered the virus avirulent for hamsters by the intraperitoneal route.
STUDIES ON THE FLEXNER GROUP OF DYSENTERY BACILLI
Authors: Perlman Ely , Goebel Walther F. 
Published: June 2004

1. The toxicity of killed dysentery bacilli can be ascribed to the somatic antigen. Antibodies to intact dysentery bacilli apparently contain no toxin-neutralizing antibodies other than those which precipitate the purified somatic antigen.
2. The serological properties of dysentery bacilli are determined by the specific somatic antigen. The specificity and cross-reactivity of the somatic antigen are dependent upon the carbohydrate moiety of the molecular complex.