bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ROLE OF THE KIDNEY IN THE CATABOLISM OF BENCE JONES PROTEINS AND IMMUNOGLOBULIN FRAGMENTS
Authors: Wochner R. Dean , Strober Warren , Waldmann Thomas A.
Published: June 2004

The role of the kidney in the catabolism of Bence Jones proteins, intact IgG molecules, and isolated L chains, Fab and Fc fragments of IgG, was studied. The proteins were purified, radioiodinated, and their survival times measured in nephrectomized, ureter-severed, and control mice.

Active endogenous catabolism was the major factor in overall Bence Jones metabolism since excretion as proteinuria accounted for less than 25% of the total metabolism. The survival times of λ- and κ-type human Bence Jones proteins and the Bence Jones protein produced by mice with MPC-2 plasma cell tumor were exceedingly short in both unoperated and ureter-severed mice, with 50% of the injected protein catabolized in from 0.8–1.6 hr. In contrast, the survival of Bence Jones protein was markedly prolonged in nephrectomized animals, with 50% of the injected dose catabolized in from 9 to 17 hr. This ten-fold decrease in catabolic rate indicates that the kidneys are the major site of breakdown of Bence Jones proteins. Similar studies with other proteins indicated that the kidneys are also the major site for catabolism of isolated L chains but not of intact IgG molecules. The Fc immunoglobulin fragment was not catabolized and the Fab fragment only partially catabolized by the kidney. When ureter-severed animals were allowed to develop advanced uremia before being studied, the survival of Bence Jones protein was greatly prolonged, indicating that the catabolic process is impaired in the presence of uremia. The nature of this renal catabolism remains unknown.

These observations suggest that the Bence Jones proteins and L chains observed in the urine of patients may reflect only a small fraction of such molecules synthesized by these patients. Furthermore, they provide an explanation for the prolongation of Bence Jones protein survival and the development of Bence Jones proteinemia observed in subjects with multiple myeloma and impaired renal function.
STUDIES ON PNEUMONIA VIRUS OF MICE (PVM) IN CELL CULTURE
Authors: Harter Donald H. , Choppin Purnell W.
Published: June 2004

Pneumonia virus of mice (PVM) has been serially propagated in a line of baby hamster kidney (BHK21) cells. A maximum titer of 6.3 x 106 TCID50 per ml was obtained, and there was little variation in yield on serial passage.

PVM grown in BHK21 cells was antigenically similar to virus obtained from the mouse lung, but was somewhat less virulent for the mouse after 10 serial passages in these cells. Virus produced by BHK21 cells agglutinated mouse erythrocytes without prior heating or other treatment.

Sedimentation of PVM in the ultracentrifuge or precipitation by ammonium sulfate resulted in a loss in infectivity but an increase in hemagglutinating activity, presumably due to disruption of the virus particle. In a potassium tartrate density gradient, the major portion of infective virus sedimented at a density of approximately 1.15, and noninfective hemagglutinin, at a density of approximately 1.13. Stock virus preparations appear to contain a large amount of noninfective hemagglutinin.

The replication of PVM was not inhibited by 5-fluoro-2'-deoxyuridine, 5-bromo-2'-deoxyuridine, or 5-iodo-2'-deoxyuridine. Infected cells contained eosinophilic cytoplasmic inclusions which showed the acridine orange staining characteristic of single-stranded RNA. Foci of viral antigen were observed in the cytoplasm of infected cells by fluorescent antibody staining.

The results suggest that PVM is an RNA virus that replicates in the cytoplasm.
IMMUNOLOGICAL STUDIES CONCERNING THE NEPHRITIS OF SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Koffler David , Schur Peter H. , Kunkel Henry G.
Published: June 2004

Antibodies were eluted from the isolated glomeruli prepared from the kidneys of 10 patients with the nephritis of systemic lupus erythematosus. Antibodies reacting primarily with buffer extracts of nuclei were eluted by acid treatment, and antibodies reacting mainly with DNA and nucleoprotein were eluted with deoxyribonuclease. Quantitative immunochemical studies revealed a high concentration of antinuclear antibody per milligram of γ-globulin in glomerular eluates compared with that in the corresponding serums. The γ-globulin of two eluates was found to consist predominantly of antinucleoprotein antibody. The selective elution of antinuclear antibodies was also indicated by the absence of other serum antibodies in the eluates.

DNA antigen was demonstrated in the glomeruli of two kidneys with nephritis by means of isolated anti-DNA antibody labeled with fluorescein. In one of these cases, anti-DNA antibodies were also found concentrated in the glomeruli and, in the second, circulating anti-DNA antibodies were demonstrated in the patient's serum.

The immunochemical evidence for the high specific activity of antinuclear antibodies and the association of DNA antigen with DNA antibody in glomeruli add further support for the antigen-antibody complex hypothesis for renal injury in systemic lupus erythematosus.
HEMOPOIETIC SPLEEN COLONY STUDIES
Authors: Curry J. L. , Trentin J. J.
Published: June 2004

The effects of phytohemagglutinin (PHA) were studied in irradiated mice to see if a definite myeloproliferative effect could be demonstrated in vivo. The data obtained suggested the following conclusions.

PHA treatment of the bone marrow donor only, causes a consistent but slight reduction in transplantable spleen colony-forming unit (CFU) content of the bone marrow 24 hr after the last PHA injection, but no change was found in the proportion of the various colony types.

PHA treatment of the irradiated recipient of normal bone marrow causes no change in the number of spleen colonies. However, 8-day colonies are only about half normal size, are much more likely to be of mixed cell types, contain many large undifferentiated blastoid cells, but fewer transplantable CFU. The spleen sinusoids are packed with hemopoietic cells.

Spleen colonies developing in hosts receiving daily injections of PHA show, in addition to the usual spectrum of cell types, a high proportion of unusual blastoid cells resembling the PHA transformed peripheral lymphocytes seen in vitro. The function of these cells is not known, but they may represent augmented proliferation and/or transformation of stem cells.

PHA administered after irradiation significantly increased the number of endogenous spleen colonies, and, at certain doses of irradiation, improved postirradiation survival.

PHA administered before irradiation had no effect on the number of endogenous spleen colonies formed, or on postirradiation survival.

On the basis of these and other data, possible modes of action of PHA are discussed.
IN VITRO CULTIVATION AND IMMUNOFLUORESCENT STUDIES OF TRANSPLANTABLE CARCINOMAS Vx2 AND Vx7
Authors: Osato Toyoro , Ito Yohei
Published: June 2004

The Vx2 and Vx7 rabbit carcinomas, both of Shope papilloma derivation, were cultivated in vitro and studied for immunofluorescence indicative of the presence of viral antigen. The cultured Vx7 cells were characteristically pleomorphic, round or polygonal cells, and immunofluorescence was demonstrable in 5–20% of them as counted on cover slip cultures after exposure to rabbit sera containing anti-Shope papilloma virus antibody. The Vx2 cells in contrast to this were of almost uniform size and character, small and approximately round, and the specific fluorescence was found in less than 0.1% of the total number. These findings indicate that some antigenic derivation from the Shope papilloma virus is still persisting at least in some fractions of the cells, not only of Vx7 tumors but also of the Vx2 tumors, even after maintenance of the growths by transplantation for more than 20 yr. During the course of the study, two lines of the Vx7 were kept continually growing while the culture of Vx2 was discontinued at its tenth passage after an accident due to mechanical failure of the incubator. The neoplastic capacity of the Vx7 cells cultured in vitro was demonstrated by implanting these intradermally on the ears of domestic rabbits. The result was destructive carcinomas of the Vx7 sort.
ENHANCEMENT OF THE HEMOLYTIC ACTIVITY OF THE SECOND COMPONENT OF HUMAN COMPLEMENT BY OXIDATION
Authors: Polley Margaret J. , Müller-Eberhard Hans J.
Published: June 2004

A method has been described for the chemical modification of human C'2 which results in a pronounced enhancement of its hemolytic activity and a marked increase in the stability of the intermediate complex EAC'1a,4,2a prepared with the modified C'2. Both effects are fully explained by the observed increase in activity and stability of the C'3 converting enzyme, C'4,2a, following its generation with modified C'2. Evidence has been presented in support of the hypothesis that the modification resulting from treatment of C'2 with a critical concentration of iodine consists of oxidation of one or more sulfhydryl group within the molecule.
THE ROLE OF ANTI-GLOMERULAR BASEMENT MEMBRANE ANTIBODY IN THE PATHOGENESIS OF HUMAN GLOMERULONEPHRITIS
Authors: Lerner R. A. , Glassock R. J. , Dixon Frank J.
Published: June 2004

These observations established the presence of anti-GBM antibodies in the sera and/or kidneys of six humans with glomerulonephritis. Further, it seems clear that these antibodies do combine with the host's glomeruli in vivo and with GBM antigen of several species in vitro.

Transfer of acute glomerulonephritis to normal recipient monkeys was possible with serum or renal eluate IGG from the three patients with anti-GBM antibodies in whom sufficient material was available. Based on this transfer of nephritis and on the presence of these antibodies at the site of injury in the nephritic kidneys of both the patients and the recipient monkeys, it seems likely that they are at least a contributing, if not primary, cause of the glomerular injury.

The frequency of anti-GBM antibodies in human nephritis is not certain, but on the basis of preliminary observations it would appear that they are present in all cases of Goodpasture's nephritis and somewhat less than half of the cases of subacute and chronic glomerulonephritis of adults.

The nature and source of immunogen stimulating the production of anti-GBM antibodies is not known, but the presence of potentially nephritogenic GBM antigens in normal urine raises the question of possible autoimmunization.

From a practical point of view, it appears that patients forming anti-GBM antibodies may not be good candidates for renal transplantation since they are likely to produce in the transplants the nephritic changes already suffered by their own kidneys.
ULTRASTRUCTURAL LOCALIZATION OF ANTIBODY IN DIFFERENTIATING PLASMA CELLS
Authors: Leduc Elizabeth H. , Avrameas Stratis , Bouteille Michel
Published: June 2004

Antibody was localized by electron microscopy within differentiating and mature plasma cells of the spleens of hyperimmunized rabbits. Horseradish peroxidase was used as antigen. Intracellular antibody to peroxidase was revealed in glutaraldehyde-fixed tissue by coupling it with its antigen and then revealing the sites of peroxidase activity cytochemically. Antibody first appears in the perinuclear space of hemocytoblasts where it persists through differentiation into immature plasma cells, but it disappears from this site in mature plasma cells. Concomitant with the development of the ergastoplasm, antibody accumulates in many but not all of its cisternae. Antibody is present in the lamellar portion of the Golgi apparatus in all phases of plasmacytic differentiation. Mature plasma cells exhibit two types of antibody distribution, a concentration into large spherical intracisternal granules or an overflowing into all parts of the cytoplasm.
MIGRATION OF LYMPHOCYTES AND THYMOCYTES IN THE RAT
Authors: Goldschneider Irving , McGregor Douglas D.
Published: June 2004

The cellular deficit in rats thymectomized at birth is primarily one of circulating small lymphocytes. The lymphocyte deficiency is similar to that induced in adult rats by chronic drainage from a thoracic duct fistula. In both cases, the animals show a reduction of small lymphocytes in peripheral blood, thoracic duct lymph, and in circumscribed areas of lymphoid tissue. The lympocyte deficiency in lymphoid tissue can be corrected by an intravenous injection of thoracic duct lymphocytes. The evidence suggests that the deficiency is corrected by small lymphocytes.

Small lymphocytes pass from blood to lymphoid tissue along a route which includes the marginal sinus in splenic white pulp and postcapillary venules in the cortex of lymph nodes and Peyer's patches. Neither the ability of small lymphocytes to colonize lymphoid tissue nor their ability to traverse postcapillary venules are thymus-dependent phenomena. However, movement of small lymphocytes across postcapillary venules appears to modify the structure of endothelium.

Intravenously injected small thymocytes migrate to lymphoid tissue in smaller numbers than small lymphocytes inoculated by the same route. The few thymocytes which localize in lymphoid tissue follow the same pathway as circulating small lymphocytes.
VARIATION IN THE ONCOGENIC POTENTIAL OF HUMAN ADENOVIRUSES CARRYING A DEFECTIVE SV40 GENOME (PARA)
Authors: Rapp Fred , Jerkofsky Maryann , Melnick Joseph L. , Levy Barnet
Published: June 2004

The acquisition of the defective SV40 genome by a variety of human adenovirus serotypes by the process of transcapsidation has resulted in the addition of oncogenic potential for newborn hamsters to the previously nononcogenic adenovirus types 1, 2, 5, and 6. These serotypes have previously been grouped together by the high GC content of their DNA.

Transcapsidation of the SV40 genome to weakly oncogenic adenovirus types 3, 14, 16, and 21 has failed to increase their oncogenic potential although the parent adenovirus type 7 carrying PARA is highly oncogenic. These serotypes belong to the group possessing a DNA of intermediate GC content.

All the PARA-adenovirus populations, even those that were nononcogenic, were able to induce SV40 transplantation immunity and therefore carry the SV40 transplantation marker as well as the marker for synthesis of SV40 tumor or T antigen.
SPONTANEOUS AMYLOIDOSIS IN DIFFERENTLY GROUPED AND TREATED DBA/2, BALB/c, AND CBA MICE AND THYMUS FIBROSIS IN ESTROGEN-TREATED BALB/c MALES
Authors: Ebbesen P.
Published: June 2004

Sex-segregated grouping of DBA/2, BALB/c, and CBA males caused rapid amyloid development and early death as compared with segregated grouped females or with males living individually in cages with several females. Grouping of several males in a cage with females also caused early death in amyloidosis indicating that the exposure of males to males and not the sexual isolation was important for the amyloid development. Both reserpine treatment and castration prolonged the survival time of sex-segregated grouped males. Estrogen treatment retarded amyloid development in sex-segregated males while spayed and androgen-treated spayed females showed only small amounts of amyloid. Treatment with chlortetracycline did not prevent amyloid development in grouped males. Thymectomy of sex-segregated males at 1 month of age gave inconclusive evidence of a prolongation of survival time. Egg-transferred DBA/2 mice reacted as conventional DBA/2 mice when grouped by sex segregation. Cells with abundant PAS-positive cytoplasm were found in the spleen, liver, and ovaries of mice of all strains but most prominently in CBA mice. Evidence for a direct conversion of these cells to amyloid was found. Estrogen-treated BALB/c males developed testicular tumors and thymus alterations including necrosis and depletion of lymphocytes, depletion of PAS cells, formation of large cysts containing necrotic nuclei, and intralobular fibrosis.
ULTRASTRUCTURAL STUDIES OF HUMAN AND RABBIT αM-GLOBULINS
Authors: Bloth Björn , Chesebro Bruce , Svehag Sven-Eric
Published: June 2004

Electron micrographs of isolated human α2M-molecules, obtained by the negative contrast technique, revealed morphologically homogenous structures resembling a graceful monogram of the two letters H and I. The modal values for the length and width of the α2M particles were 170 A and 100 A, respectively. Purified rabbit αmacroglobulins contained about 80% α1M- and 20% α2M-globulins. The isolated rabbit α1M- and α2M-molecules were morphologically indistinguishable from one another and from human α2M-molecules.

Preliminary immunoprecipitation studies demonstrated that the two rabbit αM-globulins were antigenically different. Sedimentation constant determinations gave s20, w values of 18.8 and 18.2 for rabbit α1M and α2M, respectively.
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Dubos René , Schaedler Russell W. , Costello Richard
Published: June 2004

Newborn specific-pathogen-free mice (SPF) were separated from their mothers shortly after birth and immediately reallocated at random to foster mothers, each of which received eight young. Under these conditions, the growth rate and adult size of the young were profoundly and lastingly conditioned by some unidentified influence exerted by the foster mother.

In SPF mice nursed by their own mothers, the diet of the latter during gestation and lactation, or during lactation alone, conditioned the weight of the young at weaning time, and throughout their whole life span.

Lasting depression of growth has been achieved by minor alterations of the dam's diet, for example by lowering its content in magnesium, or in lysine and threonine. The growth-depressing effect so achieved persisted throughout the whole life-span of the young, even though they were given at weaning time and constantly thereafter unlimited amounts of an optimum diet.

In contrast, the weight-depressing effect of a diet deficient in lysine and threonine administered to adult animals was completely and rapidly reversible when a complete diet was later substituted for the deficient one.

Depression of growth resulting from nutritional experiences during gestation or lactation did not seem to affect adversely the health of the young, or to decrease their longevity. In fact, the results of two experiments in which the animals nursed by mothers on different diets, were kept undisturbed and on optimum diets throughout their whole life span, suggest that the smaller animals had a greater average life expectancy than the larger ones.
EXPERIMENTAL CHRONIC GLOMERULITIS
Authors: Pincus Theodore , Haberkern Roy , Christian Charles L.
Published: June 2004

Three of 16 rabbits injected (intravenously) daily with crystalline bovine serum albumin (BSA) for periods in excess of 10 wk developed chronic glomerulonephritis. In vivo, animals with chronic proteinuria formed variable quantities of soluble complex after injection of antigen while animals without proteinuria exhibited rapid removal of the injected BSA. In vitro studies demonstrated that a major part of the antibodies produced by rabbits with chronic nephritis lacked precipitating properties. Interpretations of these observations were presented in the discussion.

It is suggested that, in addition to quantity, quality of antibody plays an important role in the development of chronic serum sickness. Complexes formed with nonprecipitating antibody, which are less rapidly removed from circulation, would have a greater opportunity to deposit in glomeruli and induce inflammation.
AN APPROACH TO THE QUANTITATION OF IMMUNOGENIC ANTIGEN
Authors: McConahey Patricia J. , Cerottini Jean-Charles , Dixon Frank J.
Published: June 2004

Using passively administered isotope-labeled anti-KLH to suppress the antibody response of rabbits to KLH, we have attempted to estimate the amount of antigen actually involved in stimulating antibody formation. Single and paired label tracer studies of passively administered anti-KLH IgG indicated that from 0.7 to 2.9 µg were utilized or involved by the antigen in the course of a 90% suppression of the response to 2 mg KLH. Tracer studies of labeled anti-KLH F(ab')2 fragments revealed the retention of from 2 to 3 µg of these fragments in the entire rabbit during a 60% suppression of the response to 1 mg KLH. Based on previously determined ratios of mixtures of KLH and suppressive amounts of anti-KLH in adjuvant, the antibody utilization data were converted to the probable amount of antigen or immunogen involved. It appears that after an injection of 2 mg of KLH approximately 0.2–0.5 µg of antigen persisted and reacted with antibody given 24 hr later. Since all of this persisting, reactive antigen may not be immunogenic, the above estimate of immunogen is probably high, but may serve to establish upper limits for the amounts of immunogen involved in stimulating antibody formation and provide a meaningful frame of reference for antigen tracer studies.
ELECTRON MICROSCOPIC LOCALIZATION OF THE NEPHROTOXIC ANTIBODY IN THE GLOMERULI OF THE RAT AFTER INTRAVENOUS APPLICATION OF PURIFIED NEPHRITOGENIC ANTIBODY-FERRITIN CONJUGATES
Authors: Vogt Arnold , Bockhorn Hermann , Kozima Keniti , Sasaki Masamichi
Published: June 2004

Nephritis in rats was induced by intravenous injection of purified ferritin-conjugated rabbit and duck nephrotoxic globulin.

Using the fluorescent antibody technique, the same capillary pattern was found as that in glomeruli of rats receiving uncoupled nephrotoxic globulin.

Electron microscopy revealed a heavy accumulation of the basement membrane-fixed antibody almost exclusively at the endothelial side. A higher concentration of ferritin was demonstrable in the peripheral basement membrane.

The once-fixed antibody remained at the site of reaction though decreasing with time. The half-disappearance time seemed to be shorter than that of the uncoupled nephrotoxic globulin.

No difference in localization was observed between rabbit and duck antibody.

At least 40 basement membrane-fixed antibody molecules from the rabbit per 3000 mµ2 of filtration surface were needed to cause immediate nephritis. To induce nephritis using duck antibody, a greater number of basement membrane-fixed antibody seemed to be necessary.

No evidence of specific reaction with constituents of glomerular cells was obtained.
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: Pappenheimer A. M. , Brown Robin
Published: June 2004

Using the technique of radioautography, it has been shown that a probable maximum of only 25–50 molecules iodine-125-labeled toxin per cell is bound by human HeLa cells treated with approximately 107 molecules of toxin per cell, or just under one saturating dose. Radioautographs of sections from labeled cells locate most if not all of the toxin molecules fixed to the outer cell membrane. Under identical conditions far less label is taken up by mouse L cells. It is probable that the resistance of this species to diphtheria toxin can be accounted for in terms of the failure of mouse cells to bind the toxin protein.

The irreversible inhibition of protein synthesis in a living cell culture by a few molecules of toxin located at the cell surface is discussed in relation to the known interaction between toxin, NAD, and transferase II in mammalian cell extracts.
ABNORMALITIES OF IN VITRO LYMPHOCYTE RESPONSES DURING RUBELLA VIRUS INFECTIONS
Authors: Olson George B. , Dent Peter B. , Rawls William E. , South Mary Ann , Montgomery J. R. , Melnick Joseph L. , Good Robert A.
Published: June 2004

In vitro rubella virus infections of lymphocytes from normal adult humans impaired their responsiveness to phytohemagglutinin (PHA) stimulations; a situation which seemed analogous to the PHA unresponsiveness of peripheral lymphocytes from babies with the congenital rubella syndrome. Such in vitro viral infection of normal cells also decreased the synthesis of normal nucleic acids and structural proteins, and abrogated the enhanced DNA synthesis induced by pokeweed and specific antigen stimulations. Furthermore, it was shown that live rubella virus, but not ultraviolet-irradiated virus, was necessary for the impaired mitogenic responses of normal leukocytes.

These observations are interpreted to favor the view that the virus achieves its inhibitory effect on the action of mitogens by interference either directly or indirectly at an intracellular site. Such an action could reduce the functional potential of lymphocytes and impair their effectiveness as immunologically competent cells or as effectors in immunologic reactions.
IMMUNOCHEMICAL STUDIES ON THE CROSS-REACTIVITY BETWEEN STREPTOCOCCAL AND STAPHYLOCOCCAL MUCOPEPTIDE
Authors: Karakawa Walter W. , Braun Dietmar G. , Lackland Henry , Krause Richard M.
Published: June 2004

Particulate mucopeptides of Group A-variant streptococci and Staphylococcus aureus, solubilized by ultrasonic treatment, give a precipitin reaction with the sera of rabbits immunized with Group A-variant streptococci. γ-G globulin antibodies have been recovered from these sera which react with the mucopeptides but not with the Group A-variant carbohydrate.

The immunochemical basis for the cross-reactivity between the streptococcal and staphylococcal mucopeptides was investigated in detail. Three chemically different fractions have been isolated from enzymatic digests of staphylococcal mucopeptide and were employed as haptenic inhibitors of the precipitin reaction. A fraction consisting of the peptide moiety of mucopeptide was the strongest inhibitor, whereas the hexosamine-rich fraction was less effective. The third fraction, rich in glycine, was least effective.

It is suggested that the immunologic cross-reactivity between streptococcal and staphylococcal mucopeptide is due to the fact that these two substances contain chemically similar tetrapeptides. The hexosamine polymer which is identical for both mucopeptides may also contribute to their cross-reactivity.
QUANTITATIVE ASSAY OF ANTIGENIC DISPARITY AT HL-A—THE MAJOR HISTOCOMPATIBILITY LOCUS IN MAN
Authors: Albertini Richard J. , Bach Fritz H.
Published: June 2004

We have extended the method of one-way stimulation in mixed leukocyte culture tests as previously described to quantitate different degrees of stimulation. To demonstrate that the amount of stimulation is immunogenetically meaningful, siblings and parents in families in whom genotyping on the basis of leukocyte antigen data was possible were tested. The prediction that cells of siblings differing from the responding sibling by both alleles at HL-A, stimulate more than do cells of siblings differing by only one allele, was realized in every case. One exception, with cells of a parent, is discussed. It is stressed that the differences measured here are probably fairly strong ones in the majority of cases, and that lesser differences cannot yet be detected reproducibly.
DISTRIBUTION OF ANTIBODY-FORMING CELLS OF DIFFERENT SPECIFICITIES IN THE LYMPH NODES AND SPLEENS OF GUINEA PIGS
Authors: Green Ira
Published: June 2004

The distribution of antibody-forming cells of different specificities in the lymph nodes and spleens of guinea pigs immunized with two separate antigens or with antigens bearing two determinants was studied. When animals were immunized with two soluble protein antigens or antigens in which the two antigenic determinants were on the same molecule, antibody-forming cells of different specificities were always randomly intermixed. However, when animals were immunized with two heat-aggregated particulate protein antigens and then boosted with soluble protein antigens, cells of different specificities were often seen to occur in groups.

These results suggest that antibody-forming cells may not arise by the antigen-stimulated proliferation of precommitted antibody-forming cells, but rather antibody-forming cells arise by a transformation of uncommitted precursor cells as the result of their interactions with a locally produced material derived from the processing of antigen.
STUDIES ON THE ANTI-INFLAMMATORY ACTION OF 6-MERCAPTOPURINE
Authors: Hurd Eric R. , Ziff Morris
Published: June 2004

The mechanism of action of 6-mercaptopurine (6-MP) on an egg albumin-induced inflammatory lesion in the skin has been studied in rabbits treated with 6-MP in a daily dosage of 18 mg/kg. Relative to control animals, significant decreases in the numbers of large lymphocytes and monocytes in the blood were observed in the 6-MP-treated animals by the 9th day of treatment, without significant decrease in the numbers of polymorphonuclear leukocytes and small and medium lymphocytes. Concurrently, a significant decrease was also seen in the percentage of tissue mononuclear cells in the inflammatory skin lesion. There was a highly significant correlation between the numbers of monocytes in the blood and the per cent of mononuclear cells in the lesion. A mean of 52% of the mononuclear cells in the tissue lesion phagocytosed carbon offering further evidence that the major cell involved was the blood monocyte.

In vitro incorporation of 3H-Tdr by blood mononuclear cells was significantly reduced in the 6-MP-treated animals as determined by scintillation counting and radioautography. The large lymphocyte was the predominant cell type which was labeled in vitro. Small lymphocytes and monocytes were rarely labeled.

The data obtained suggest that the anti-inflammatory effect of 6-MP, reflected in these experiments by a decrease in mononuclear cells in a tissue lesion, results from suppression of a bone marrow response to local inflammation, affecting principally proliferating precursors of blood monocytes and large lymphocytes. The possible importance of this action of 6-MP in the treatment of inflammatory and immunologically mediated disease is discussed.
CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE
Authors: Martin W. J. , Miller J. F. A. P.
Published: June 2004

In this series of papers it has been shown that the immune response of mice to sheep erythrocytes requires the participation of two classes of lymphoid cells. Thymus-derived cells initially react with antigen and then interact with another class of cells, the antibody-forming cell precursors, to cause their differentiation to antibody-forming cells.

Antilymphocyte globulin depressed the ability of mice to respond to sheep erythrocytes. This effect was more marked when the antigen was injected intraperitoneally than intravenously, and occurred only when the antilymphocyte globulin was given before or simultaneously with antigen. Injection of thymus cells restored to near normal the ability to respond to an intravenous injection of sheep erythrocytes. Spleen cells from antilymphocyte globulin-treated mice gave a weak adoptive immune response in irradiated recipients. The addition of thymus cells however enabled a response similar to that given by normal spleen cells.

When thymectomized irradiated recipients were used, normal spleen cells continued to give a higher response to a challenge of sheep erythrocytes at 2 and 4 wk postirradiation than did spleen cells from ALG-treated donors. This result is more consistent with the notion that thymus-derived target cells are eliminated, rather than temporarily inactivated, by antilymphocyte globulin.

These findings suggest that, in vivo, antilymphocyte globulin acts selectively on the thymus-derived antigen-reactive cells.
RELATION BETWEEN EPSTEIN-BARR VIRAL AND CELL MEMBRANE IMMUNOFLUORESCENCE IN BURKITT TUMOR CELLS
Authors: Klein G. , Pearson G. , Henle G. , Henle W. , Diehl V. , Niederman J. C.
Published: June 2004

Blastoid cell cultures derived from leukocytes of patients in the acute stage of infectious mononucleosis (IM) and harboring Epstein-Barr (EB) virus in at least 1% of the cells were found to possess antigens in their membranes which presently are indistinguishable from those detected in Burkitt's lymphoma (BL) cells by the techniques employed. It was noted that, in the course of IM, antibodies are formed which react in indirect immunofluorescence tests with membrane antigens of live cells from Burkitt tumor lines as well as from IM leukocyte cultures, including an autochthonous line in the case of one patient. Sets of sera from IM patients were tested which included a serum collected weeks to years before onset of illness. In the majority of these the pre-IM serum failed to react in membrane immunofluorescence (MIF) tests with any of several Burkitt tumor cell lines employed, but in some cases the presera reacted with cells of some but not others of the lines. Possible explanations for these discrepant results have been discussed.

The antibodies involved in the MIF test are evidently distinct from those responsible for the EBV and heterophile reactions. Maximal MIF activity is attained long after the other two antibodies have reached maximal titers and antibodies to EBV and membrane antigens seem to persist for years whereas the heterophile reaction turns negative within a few months.
THE INTERACTION OF HUMAN MONOCYTES AND LYMPHOCYTES
Authors: Cline Martin J. , Swett Virginia C.
Published: June 2004

Monocytes isolated from the peripheral blood of tuberculin-positive and tuberculin-negative donors were exposed to PPD, extensively washed, and incubated with autologous or homologous lymphocytes. Lymphocyte transformation was measured morphologically and by incorporation of 14C-labeled thymidine.

Monocytes from tuberculin-positive subjects induced transformation of autologous lymphocytes in 19 of 29 experiments. Studies to define the optimal conditions of exposure to monocytes to PPD and to autologous lymphocytes showed that viable, metabolically intact monocytes are required. A ratio of only 1 monocyte to 100 lymphocytes sufficed to induce transformation; neutrophils were inactive. In general, PPD-sensitized monocytes failed to induce transformation of homologous lymphocytes from either tuberculin-positive or tuberculin-negative subjects. Direct contact between monocytes and lymphocytes was required for consistent transformation, and islands of transforming lymphocytes were observed around a central core of monocytes.
AN ANALYSIS OF THE TOXIC ACTIONS OF PURIFIED STREPTOLYSIN O ON THE ISOLATED HEART AND SEPARATE CARDIAC TISSUES OF THE GUINEA PIG
Authors: Reitz Bruce A. , Prager Denis J. , Feigen George A.
Published: June 2004

The response of isolated guinea pig hearts to perfusion with purified streptolysin O is characterized by a rapid, but transient, decrease in rate and amplitude of contraction; these reactions are superimposed upon a gradual, irreversible, loss of ventricular contractility. At ventricular standstill, the atria continue to beat spontaneously in a normal way. Isolated ventricle strips prepared from such preparations can be driven electrically, and their behavior is functionally indistinguishable from that of similar preparations made from normal hearts.

Tests on spontaneously beating isolated atrial pairs show that the toxin induces a dose-dependent, reversible, decline in rate and amplitude which is accompanied by a marked, but transient, increase in the velocity of repolarization of the intracellular potential. The atrial reactions were completely blocked by atropine and potentiated by eserine.

Acetylcholine was detected in the perfusates obtained by incubating a large pool of atrial tissue with active toxin, supporting the inference that the transient mechanical and electrophysiological reactions to toxin might be consequences of the release of acetylcholine from these tissues by the active toxin.

Control studies showed that only the active toxin had the capacity to induce the cardiac responses. The toxin was active only in the reduced but not the oxidized form. The effects of the active toxin were modified if it were heated prior to challenge, and they could be neutralized by specific antiserum and inhibited by cholesterol.

Since the driven ventricle strip was mechanically and electrophysiologically insensitive to streptolysin O, the irreversible changes in the whole heart must have occurred because of a defect in the atrioventricular conduction system.
BONE MARROW AS SOURCE OF CELLS IN REACTIONS OF CELLULAR HYPERSENSITIVITY
Authors: Lubaroff David M. , Waksman Byron H.
Published: June 2004

Splenectomy or thymectomy of adult Lewis rats following sensitization with tubercle bacilli did not affect their ability to develop delayed skin lesions upon skin testing with PPD. The presence of the thymus also had no significant effect on reactivity of the recipients in passive transfer experiments. The passive transfer of tuberculin hypersensitivity with sensitized lymph node cells to thymectomized, irradiated recipients depended on the simultaneous or prior injection of normal bone marrow cells. When lymph node cell transfer was performed shortly after irradiation and injection of marrow, high doses of marrow cells (3.5–4.0 x 108 were required to permit eliciting reactions of reasonable intensity. If, however, periods of 7–10 days elapsed between the injection of bone marrow and sensitized lymph node cells, lower doses of marrow were sufficient for comparable reactions. Normal thymus, spleen, lymph node, or peritoneal exudate cells, even at high doses could not be substituted for the bone marrow in producing good tuberculin reactions.
SPECIFICITY OF THE IMMUNE RESPONSE TO THE 2, 4-DINITROPHENYL AND 2, 4, 6-TRINITROPHENYL GROUPS
Authors: Little J. Russell , Eisen Herman N.
Published: June 2004

The principal results of the present study are: (a) the failure to find an antibody subset that binds a cross-reacting ligand better than the comparable homologue in spite of the use of isolation methods that select for such antibody molecules; (b) the isolation of antibody subsets with virtually indistinguishable average intrinsic association constants for homologous and cross-reacting ligands, but which nevertheless have physical properties (Qmax and relative fluorescence coefficient) that readily distinguish these subsets according to their origin in response to antigenic stimulation with DNP- or with TNP-protein; (c) the demonstration, by precipitin reaction and measurement of association constants for homologous and cross-reacting haptens, of generally greater cross-reactivity among high affinity anti-DNP and anti-TNP antibodies, i.e. low affinity antibodies are generally more discriminating; (d) the selection of anti-DNP and anti-TNP antibody subsets that are distinctive in their ability to show spur formation in gel diffusion reactions with homologous and cross-reacting antigens.

These results suggest that in the initial cellular response to antigenic stimulation, DNP-BγG and TNP-BγG stimulate virtually nonoverlapping sets of antigen-sensitive cells, despite the great similarity of these two immunogens. With prolonged stimulation this specificity wanes, giving rise to a more degenerate response evident in the greater cross-reactivity of the antibodies produced later in immunization.
CELL INTERACTIONS IN THE PRIMARY IMMUNE RESPONSE IN VITRO: A REQUIREMENT FOR SPECIFIC CELL CLUSTERS
Authors: Mosier Donald E.
Published: June 2004

Mouse spleen cells were found to associate in cell clusters during the primary immune response to sheep erythrocytes in vitro. About 10% of the cell clusters had the following unique properties; (a) they contained most, if not all, antibody-forming cells, (b) they contained only cells forming antibody to one antigen when cell cultures were immunized with two antigens, (c) the cells in clusters reaggregated specifically after dispersion, and (d) the specific reaggregation of clusters appeared to be blocked by antibody to the antigen. The integrity of cell clusters was required for the proliferation of antibody-forming cells, and prevention of clustering by mechanical means or by excess antibody blocked the immune response. Antibody and antigenic determinants on the surfaces of cells probably provide the basis for interaction. The unique microenvironment of cell clusters was essential for the primary immune response in vitro.
BIPHASIC PATTERN OF THYMUS REGENERATION AFTER WHOLE-BODY IRRADIATION
Authors: Takada Akikazu , Takada Yumiko , Huang Chester C. , Ambrus Julian L.
Published: June 2004

Whole-body irradiation of mice with 300 or 400 R causes a precipitous fall in thymus weight, followed by an increase in the mitotic index and an almost complete restoration of thymus mass. This phase is followed by a secondary fall in thymus weight and gradual recovery. This secondary fall can be prevented by intravenous injection of bone marrow or shielding of the hind limbs during irradiation. The hypothesis is proposed that the thymus depends on the migration of cells from the bone marrow to the thymus for the maintenance of its cell population.

Bone marrow cells with chromosome markers injected intravenously into normal or lightly irradiated (150 R) animals do not populate the host bone marrow to any significant degree. After whole-body irradiation with heavy doses (400 R), donor cells dominate the marrow. There may be a competition between dividing cells in the bone marrow which regulates proliferation of hemic cells.

Bone marrow cells with marker chromosomes do not repopulate the thymus in irradiated animals until long after repopulating the bone marrow. It is possible that these cells have to pass through the marrow or the blood-marrow barrier to acquire characteristics needed for entering the thymus.

After whole-body irradiation with 500 R or more, the first phase of regeneration of the thymus, represented by an increase in the mitotic index, does not occur to a significant degree. Apparently cells in the thymus capable of proliferation have been largely eliminated, and restoration of organ mass depends chiefly on seeding from other sources, probably the bone marrow.

After whole-body irradiation with 200 R, only the first phase of thymus weight loss and regeneration takes place. Probably bone marrow injury is too small to interfere with the supply of cells repopulating the thymus.
DISSOCIATION OF HEMOLYTIC AND LYMPHOCYTE-TRANSFORMING ACTIVITIES OF STREPTOLYSIN S PREPARATIONS
Authors: Taranta Angelo , Cuppari Girolamo , Quagliata Franco
Published: June 2004

The ability of streptolysin S preparations to induce high percentages of transformation in human peripheral blood lymphocytes was confirmed in a series of apparently healthy donors. Transforming activity was not demonstrated in the two media used for streptolysin S production, nor in control preparations in which a strain each of Streptococcus viridans, Staphylococcus aureus (nonhemolytic), and Diplococcus pneumoniae was substituted for the beta hemolytic streptococcal strain used for streptolysin S production.

The relation of the hemolytic activity to the lymphocyte transforming activity of streptolysin S preparations was studied by means of inactivation and fractionation experiments. Heating produced a loss in both activities, but more in the hemolytic than in the transforming activity. The transformation obtained with a heated preparation had a high degree of correlation with that obtained with the unheated preparation in a series of normal subjects and patients with various rheumatic diseases, whose lymphocytes were often less responsive to stimulation with streptolysin S preparations (both heated and unheated) than the lymphocytes of the normal subjects studied. Treatment of streptolysin S preparations with chymotrypsin, vegetable lecithin, or trypan blue (the latter in minute amounts) resulted in preparations with no detectable hemolytic activity but with undiminished lymphocyte transforming activity. Chromatographic fractionations on DEAE-Sephadex columns yielded fractions endowed with transforming but not with hemolytic activity, and other fractions endowed with hemolytic but not with transforming activity. The recovery of the hemolytic activity was not complete and quantitation of the recovery of the transforming activity was not attempted.

These experiments indicate that the hemolytic and transforming activities of streptolysin S preparations are independent of each other, and specifically that they are the attributes of two different streptococcal products, one of which is streptolysin S. The other is a nonhemolytic streptococcal product present in streptolysin S preparations but previously unrecognized. Some implications of these findings are discussed.
RELATION BETWEEN EPSTEIN-BARR VIRAL AND CELL MEMBRANE IMMUNOFLUORESCENCE IN BURKITT TUMOR CELLS
Authors: Klein G. , Pearson G. , Henle G. , Henle W. , Goldstein G. , Clifford P.
Published: June 2004

Sera from patients with Burkitt's lymphoma (BL), infectious mononucleosis (IM), carcinoma of the postnasal space (Ca PNS), and various controls were investigated for antibodies against the Epstein-Barr virus (EBV) by immunofluorescence on acetone-fixed smears (5) and for antibodies against the distinctive antigenic sites expressed on the surface of viable lymphoblastoid cells within EBV-carrying culture lines (1). The latter were studied by the blocking of direct membrane staining with FITC-conjugated Mutua serum. This serum has been derived from a Burkitt's lymphoma patient in long-term regression after chemotherapy and is free from detectable isoantibodies. It has been used previously as a standard of reference to demonstrate the presence of the membrane antigen(s) on all lines derived from BL biopsies and leukocytes from IM patients. It was found that 102 of 279 (37%) of the sera tested had high anti-EBV titers (≧80) and high membrane-blocking (Bl > 0.5) activity, 124 of 279 (44%) of the sera were low in both tests, 22 of 279 (8%) had low EBV titers (≦80), in spite of a high blocking index, and 31 of 279 (11%) of the sera were low in blocking activity (<0.5), in spite of a high EBV titer. The two tests thus gave concordant results with 81% and discordant with 19% of the sera.

The majority of sera from BL patients were high in both tests. IM sera also showed a relationship between the two antibody activities but, in general, both activities were lower than in BL cases. Ca PNS sera seemed to fall into two main groups: (a) high anti-EBV, high blocking or (b) low anti-EBV, low blocking. Control sera, including four isoantisera, showed predominantly low reactivities in both tests.
THE X-Y-Z SCHEME OF IMMUNOCYTE MATURATION
Authors: Byfield Patricia , Sercarz Eli
Published: June 2004

Short-term IgM memory is established within 1 day after primary injection. This 1 day priming is independent of cell division as it can take place in the pressence of methotrexate or hydroxyurea.

The primary response involves a similar 1 day nonproliferative phase. On the contrary, cells responding to a second injection of antigen after short priming intervals begin to proliferate within hours. This implies a qualitative difference between the antigen-sensitive cells in primed and normal animals.

After 1 day, further proliferative expansion of memory can occur, which is probably antigen dependent. The response to several dose regimens indicates that repeated antigenic contact is needed to maintain the IgM response.