bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ROLE OF THE MICROBIAL FLORA IN UREMIA
Authors: Carter Darryl , Einheber Albert , Bauer Heinz , Rosen Hyman , Burns Willard F.
Published: June 2004

Uremic colitis of varying severity occurred in the majority of conventionalized rats dying after removal of both kidneys, but was not found in uremic conventionalized and germfree rats sacrificed preterminally, or in germfree and limited-flora rats dying from uremia, or in any of the controls. The lesions were restricted to the cecum and their incidence and severity paralleled a shorter duration of survival. Cardiovascular damage including focal myocardial necrosis and calcification and patchy aortic and coronary calcification were observed in uremic rats regardless of their microbial status. These lesions had a higher incidence, developed more rapidly, and were more severe in the germfree and limited-flora rats than in the conventionalized animals. The presence or severity of the lesions, however, did not correlate with survival time of rats dying from uremia or with total plasma calcium and inorganic phosphorus levels of individual animals. Generalized necrotizing arteritis was not observed. Wound healing was poor in all uremic rats regardless of microbial status. Focal infection was noted in a few conventionalized rats dying from uremia, did not correlate with survival time, and was absent in all other groups.

Comparison of biochemical findings between uremic germfree and conventionalized rats show a higher blood urea nitrogen and elevated plasma indoxyl sulfate in the presence of a microbial flora and a greater amount of plasma inorganic phosphorus in its absence. Uremia resulted in a decrease in hematocrit and increase in plasma and muscle potassium that were similar for germfree and conventionalized rats. Plasma and muscle sodium, total plasma calcium, glucose, and total protein were essentially unchanged by microbial status or uremia.

Because the foregoing differences in the metabolic and histopathologic changes of uremia are linked to the known difference in microbial status of the fasting bilaterally-nephrectomized rats that were studied, they are a tangible indication of ways by which the indigenous microbial flora and its composition may affect the course of acute uremia.
THE RENAL LESION ASSOCIATED WITH HEMOGLOBINEMIA
Authors: Jaenike John R. , Schneeberger Eveline E.
Published: June 2004

Histological studies have been performed on experimental acute renal failure induced by intravenous injection of hemoglobin in rats. These have been correlated with alterations in renal excretory function, assessed by the measurement of inulin clearance, at various stages of the lesion. The most prominent morphological changes during the first 24 hr after hemoglobin injection, when inulin clearance is most markedly suppressed, are: the presence of hemoglobin within the lumen of small intrarenal vessels, particularly the vasa recta; hemoglobin cast formation involving predominantly the thick ascending limbs of the loops of Henle; and evidence of injury of the epithelium of the proximal tubules and thick ascending limbs. Notably absent during this stage of the lesion are marked tubular dilatation, interstitial edema, and cast formation in the distal collecting ducts. The considerable recovery of function which occurs at 72 hr is accompanied by a marked reduction in involvement of the vasa recta. Standard sections and microdissection reveal many markedly dilated proximal tubules at this stage of the lesion, suggesting obstruction of filtering nephrons.

These data have led to a tentative hypothesis regarding the pathogenesis of renal failure in this experimental lesion. It is suggested that renal ischemia and failure of glomerular filtration are the primary factors responsible for the early and severe impairment of renal function, and that these are related to intravascular aggregation of hemoglobin pigment. As this defect recedes, tubular obstruction by hemoglobin casts prevents restitution of excretory function in a variable fraction of the nephrons. The latter accounts for the relatively prolonged, moderate reduction in inulin clearance associated with the late stages of this lesion. These hypotheses form the basis for a continuing study of this renal lesion.
CHARACTERISTICS OF STREPTOCOCCAL GROUP-SPECIFIC ANTIBODY ISOLATED FROM HYPERIMMUNE RABBITS
Authors: Osterland C. Kirk , Miller Edward J. , Karakawa Walter W. , Krause Richard M.
Published: June 2004

Intravenous immunization of New Zealand red rabbits with streptococcal group-specific bacterial vaccines yielded sera which possessed markedly elevated γ-globulin. The sera of one rabbit immunized with Group A-variant vaccine possessed 55 mg/ml of γ-globulin. The bulk of this γ-globulin, identified as γG-globulin, was homogeneous by zone electrophoresis and of specificity directed against the Group A-variant carbohydrate antigen. L chains isolated from specific antibody obtained from an immune precipitate were distributed as a single band on starch gel electrophoresis, whereas the normal γ-globulin traveled as a diffuse smear. These data suggest that the rabbit streptococcal Group A-variant antibodies possess a limited range of physicochemical properties and electrophoretic mobility compared to that generally observed for the normal complement of γ-globulin.
THE IGA SYSTEM
Authors: South Mary Ann , Cooper Max D. , Wollheim Frank A. , Hong Richard , Good Robert A.
Published: June 2004

1. Five patients with congenital or acquired agammaglobulinemia, lacking detectable IgA in serum or saliva, were transfused with 1 to 2 liters of normal plasma. In 2 of these patients IgA was demonstrated in parotid saliva collected after transfusion, but in none of the 5 was salivary IgG or IgM found. This observation indicates the selective transport of IgA into saliva.

2. The observation by others of an immunochemical difference between serum and sahvary IgA globulin was confirmed. In contrast to serum IgA, salivary IgA is attached to a protein having antigenicity which migrates as a gamma1 globulin. We have termed this protein component "transport piece".

3. The transport piece has been found in an unbound form in the saliva of persons completely lacking IgA: agammaglobulinemic patients, ataxia-telangiectasia patients, a healthy person lacking IgA, and a newborn infant. Free transport piece still occurs in the normal child's saliva after IgA production begins. By adulthood there is usually no free transport piece in the saliva.

4. Heat-aggregated salivary IgA, like heat-aggregated serum IgA, does not fix complement.

5. Our findings offer support for the view that there is a distinct local antibody system for the protection of the mucous surfaces.
RUBELLA VIRUS CARRIER CULTURES DERIVED FROM CONGENITALLY INFECTED INFANTS
Authors: Rawls William E. , Melnick Joseph L.
Published: June 2004

Spontaneous rubella carrier cultures derived from tissues of infants with congenital rubella were studied in an attempt to elucidate a possible mechanism for viral persistence observed in these infants. Chronically infected cells were found to have a reduced growth rate and the cultures appeared to have a shortened life span. The rubella carrier state was not dependent on serum inhibitors or rubella antibodies. Virtually every cell in the carrier population was found to be producing virus. The carrier cultures could not be cured by rubella antibodies. The rubella-infected cells were resistant to superinfection with vesicular stomatitis virus and herpes simplex virus but were susceptible to infection with echovirus 11. The replication of vesicular stomatitis virus was apparently blocked at an intracellular site, for the virus readily adsorbed to the chronically infected cells and entered into an eclipse phase; however no infectious virus developed. No evidence of interferon production by these cells could be obtained. It is postulated that clones of rubella-infected cells in vivo, with properties similar to those in carrier cultures developed in vitro from tissues of in utero infected infants, might explain the observed viral persistence noted in congenital rubella.
COLICINE K
Authors: Hinsdill Ronald D. , Goebel Walther F.
Published: June 2004

1. The transfer of type K. colicinogeny to Shigella sonnei Phase II has been described.

2. The colicine elaborated by this microorganism is a lipopolysaccharide-protein complex which resembles the somatic antigen of the noncolicinogenic parent.

3. Although the colicine K of Escherichia coli K235 and of Sh. sonnei differ both chemically and serologically, they resemble each other in that both elicit type K colicine-neutralizing antibodies and both have the same bactericidal specificity.

4. The nature of the chemical changes brought about in the somatic antigen of Sh. sonnei through the acquisition of colicinogeny remains unknown
STUDIES OF PPLO INFECTION
Authors: Thomas Lewis , Davidson Morton , McCluskey Robert T.
Published: June 2004

Turkey poults injected intravenously with suspensions of Mycoplasma gallisepticum develop a fatal neurologic disease associated with polyarteritis affecting almost exclusively the cerebral arteries. The incubation period depends on the dose of organisms. With high doses (1010 to 1011 mycoplasmas) the birds become ill and die within a few hours; with lower doses (106 to 108) neurologic manifestations appear after 7 days. The rapid onset of neurologic signs after high doses indicates the presence of a toxin in the mycoplasma, but efforts to extract toxin from disrupted organisms or to demonstrate its presence in culture fluid free of mycoplasmas have been unsuccessful. The toxin appears to be associated only with living mycoplasmas.

The toxic component of M. gallisepticum is inactivated by heating the organisms at 50°C, disruption by repeated cycles of freezing and thawing, and exposure to specific antibody.

Treatment of turkeys with gold thiomalate furnishes partial protection against the toxic effects of large doses of mycoplasmas, and protection against the development of cerebral arteritis. Treatment with tetracycline protects completely against both toxicity and arteritis, and, when delayed, restores diseased birds to a healthy state. Cortisone, methotrexate and 6-mercaptopurine have no effect on the course or outcome of the disease.

Intracerebral injections of M. gallisepticum are less toxic and lethal than when the same dose was given by vein, indicating that the organism exerts its damaging action on blood vessels by way of the blood stream.

The arterial lesions resemble those of serum sickness, except for their distribution, and are associated with glomerular inflammatory lesions. However, for various reasons discussed, it is considered more likely that they result from a direct toxic action of living mycoplasmas on the vessels concerned than from an immunologic mechanism.
STUDIES ON HUMAN ANTIBODIES
Authors: Kaplan Manuel E. , Kabat Elvin A.
Published: June 2004

Insoluble blood group substances prepared by copolymerization of soluble blood group substances with N-carboxy-L-leucine anhydride were used to absorb blood group antibodies from two human, high-titered anti-A sera. After the absorbants were washed free of nonspecific serum proteins, blood group antibodies were eluted either with pH 3.62 acetate buffer, or at neutral pH with monosaccharide haptens of the A or B antigenic determinants (N-acetyl-D-galactosamine or D-galactose respectively). The purified anti-A antibodies were characterized, immunoelectrophoretically, as γM-, γA-, and γG-immunoglobulins. These were further separated into γM- and γG-fractions by gel filtration or density gradient centrifugation. Both γM- and one of the two γG-antibody fractions contained K and L light chain determinants; the remaining γG-fraction was comprised, almost totally, of type K molecules.

Precipitability of the purified anti-A immunoglobulins by blood group A substance varied from 43 to 89%. The agglutinating activity per unit N of the isolated γG-anti-A was found to equal, in one case, and to exceed, in the second, that of the γM-antibodies from the same individuals.

The marked differences between γM- and γG-antibody fractions in quantitative hapten inhibition studies were interpreted to mean that the antibody-combining site of the isolated eluted γG-anti-A was significantly larger than that of the eluted γM-anti-A. Whether these data connote differences in combining site size between entire immunoglobulin classes in an individual serum or simply reflect the properties of highly selected antibody populations cannot be stated at present.
THE ORIGIN AND TURNOVER OF MONONUCLEAR CELLS IN PERITONEAL EXUDATES IN RATS
Authors: Volkman Alvin
Published: June 2004

Tritiated thymidine-labeling data in individual and parabiotic rats showed that macrophages in peritoneal exudates were derived from cells in the blood which were the progeny of rapidly and continuously proliferating precursors. The characteristics of this population identify them with free macrophages studied in other sites; similarly, they can be obtained from transfused bone marrow.

Cells in the exudates which were morphologically indistinguishable from small lymphocytes were also found to have the labeling features of a rapidly proliferating population in contrast with the known kinetics of the majority of small lymphocytes in blood and thoracic duct lymph. However, experimental evidence indicated that the lymphocytelike exudate cells had emigrated from the blood and that bone marrow was a source of their precursors. These findings support the concept of the heterogeneity of lymphocytes.

The possible relationships among the mononuclear cells is discussed.
DISQUISITIONS ON ORIGINAL ANTIGENIC SIN
Authors: de St.Groth S. Fazekas , Webster R. G.
Published: June 2004

When primary immunity is boosted not by the homologous but by a crossreacting vaccine, the newly formed antibodies react better with the primary antigen than with the antigen actually eliciting the response. This phenomenon bears the name of Original Antigenic Sin (1).

It is shown that the number of antibody molecules produced against the original and the vaccinating antigen is the same; that each of these molecules is capable of reacting with both antigens; that the activity of an antiserum can be completely absorbed with either antigen; that both residual and adsorbed-dissociated fractions of antibody exhibit the same relative affinities towards the two antigens as did the native serum; that, unlike standard primary and secondary responses, the population of antibody molecules characterizing the Original Antigenic Sin is homogeneous; that each molecule has a lower equilibrium constant (i.e. higher avidity) against the original antigen than against the antigen stimulating the present response; and that all equilibrium constants are typical of secondary antibody.

It is concluded that the Original Antigenic Sin is a partial anamnestic response, a related antigen stimulating that sector only of the originally primed cells which is destined to produce cross-reacting antibody.

A hypothesis is developed according to which the basic difference between primary and secondary reactivity rests on the presence of a trapping mechanism that allows anamnestic production of antibody against lower doses of the homologous antigen. Such a mechanism is capable of cross-trapping related antigens, thus preventing a standard primary response and allowing manifestations of Original Antigenic Sin.
STUDIES ON THE INDUCTION OF IMMUNOLOGICAL UNRESPONSIVENESS TO PNEUMOCOCCAL POLYSACCHARIDE IN MICE
Authors: Siskind Gregory W. , Howard James G.
Published: June 2004

1. Comparison of dose-response curves indicated that preimmunized animals were slightly more susceptible to the induction of immunological paralysis with pneumococcal polysaccharide than were normal mice. The results also indicated that the paralysis threshold was unaltered by preimmunization.

2. Transient desensitization of immunized mice could be achieved by an amount of polysaccharide far less than that required to induce paralysis.

3. A transient phase of weak immunity was detected prior to the onset of paralysis when induced by relatively low paralyzing doses of polysaccharide.

4. No "low dose" zone of paralysis (analogous to that obtainable with certain protein antigens) could be elicited with pneumococcal polysaccharide.

5. Massive proliferation of lymphoreticular tissues induced by Corynebacterium parvum failed to raise the threshold for paralysis induction, but amplified the immune response over the entire dose-response curve. Similarly, C. parvum failed to abrogate an established state of paralysis. The results suggest that the induction of polysaccharide paralysis is related to the concentration of antigen in the animal and is not modified by the number of immunologically competent cells.
MECHANISMS OF ACQUIRED RESISTANCE IN MOUSE TYPHOID
Authors: Blanden R. V. , Mackaness G. B. , Collins F. M.
Published: June 2004

Experiments in vitro comparing normal mouse peritoneal macrophages with cells from Salmonella typhimurium-infected mice have shown that the "immune" macrophages have conspicuously enhanced microbicidal properties. Whereas normal macrophages could inactivate only 50 to 60% of intracellular S. typhimurium pretreated with immune serum, cells from infected animals killed virtually all ingested organisms and did so at an accelerated rate. Macrophages from Listeria monocytogenes-infected mice were shown to possess similarly enhanced microbicidal activity against S. typhimurium. Furthermore, the growth of S. typhimurium in the liver and spleen was more effectively restricted in Listeria-infected mice than in animals vaccinated with heat-killed S. typhimurium, even though the Listeria-infected animals possessed no demonstrable cross-reacting antibody to S. typhimurium. The lack of resistance in the mice vaccinated with heat-killed organisms could not be attributed to any deficiency of humoral factors, since the serum from these animals was as effective at promoting phagocytosis and killing by macrophages as serum from actively infected (and demonstrably resistant) mice. Conversely, Salmonella-infected mice were totally resistant to intravenous challenge with L. monocytogenes. The level of resistance in individual animals was related to the numbers of residual Salmonellae remaining in the tissues; mice with heavier residual infections being the more resistant.

Specific antiserum from mice vaccinated with heat-killed S. typhimurium was found to be significantly protective only when the intraperitoneal route of challenge was employed.

The foregoing studies have been interpreted to mean that enhancement of the microbicidal ability of macrophages is the mechanism of major importance in acquired resistance to S. typhimurium infection in mice.
PRESENCE OF TWO TYPES OF L POLYPEPTIDE CHAINS IN GUINEA PIG 7S IMMUNOGLOBULINS
Authors: Nussenzweig Victor , Lamm Michael E. , Benacerraf Baruj
Published: June 2004

Guinea pig 7S immunoglobulins (γ1 and γ2) consist of two groups of molecules (K and L) bearing different types of L chains (κ and λ). Approximately one-third of the molecules in normal guinea pig γ2-globulin bear the λ- type of L chains, and all or most of the others bear κ-chains. κ- and λ-chains have similar molecular weights.
QUANTITATIVE VARIATIONS IN L CHAIN TYPES IN GUINEA PIG ANTIHAPTEN ANTIBODIES
Authors: Nussenzweig Victor , Benacerraf Baruj
Published: June 2004

In guinea pig purified antihapten antibodies, the proportion of molecules bearing the κ- or λ-type of L chains (K or L molecules) may diverge markedly from that found in normal γ2-globulins. This has been evaluated by precipitation of I131-labeled antibody preparations using a specific anti-λ-chain antiserum. Anti-DNP antibodies isolated 3 wk after immunization of guinea pigs with DNP65-BGG antibodies, contain less than 1% of L molecules, while in pipsyl antibodies, isolated from the sera of animals immunized with pipsyl-BGG, the proportion of L molecules is significantly greater than in normal γ2-globulins.

Anti-DNP antibodies produced against conjugates of this hapten with carriers other than BGG (BSA, OVA, or poly-L-lysine) or with BGG with a small number of DNP groups (DNP10-BGG) contained a greater proportion of λ-chain bearing molecules than anti-DNP antibodies isolated from late sera of guinea pigs immunized with highly conjugated DNP65-BGG. An increased percentage of L molecules was detected in preparations of anti-DNP65-BGG antibodies isolated early (10 days), when compared to those isolated later during the course of immunization. However, the level of L molecules in all these anti-DNP antibody preparations was always considerably below that present in normal γ2-globulin. The relative amounts of L molecules in distinct immunoglobulin families (γ1 and γ2) in antibody preparations isolated from individual animals was remarkably similar.
SERUM AND URINARY LYSOZYME (MURAMIDASE) IN MONOCYTIC AND MONOMYELOCYTIC LEUKEMIA
Authors: Osserman Elliott F. , Lawlor Dolores P.
Published: June 2004

Markedly increased quantities of lysozyme have been found in the serum and urine (ranging to 2.6 g per day) of ten consecutive cases of monocytic and monomyelocytic leukemia. The enzyme has been isolated from the urine of several cases and physicochemically and immunochemically characterized. It is apparently identical to the lysozyme of normal tears, saliva, leukocytes, and serum, but structurally different from the lysozyme of hen's egg white. The activity of the human enzyme assayed with M. lysodeikticus organisms is 3 to 12 times greater than egg white lysozyme at equivalent concentrations.

An agar plate method has been developed for quantitating lysozyme activity in small samples (approximately 25 µl) of serum, urine, or other biological fluids. The range and reproducibility of this method were found to be superior to previously available lysozyme assay procedures.

Present evidence indicates that lysozyme is the principal, if not the sole, product of the proliferating monocytes in monocytic and monomyelocytic leukemia, and quantitation of serum and urine lysozyme should be a useful diagnostic procedure for these leukemias.
IMMUNOFLUORESCENT STUDIES OF HUMAN CELL CULTURES AND CHICK EMBRYOS INOCULATED WITH THE AMEBOID CELL-"LIPOVIRUS" COMPLEX
Authors: Liu Chien , Rodina Patricia
Published: June 2004

Tissue culture cells of human origin (HeLa, Lich, and AV3) were inoculated with the AL complex. By immunofluorescent staining, AL complex antigen was detectable in the cytoplasm of infected cells as punctate fluorescent granules during the early stage and as homogeneous fluorescence during the late stage of infection. By combining fluorescence and phase-contrast microscopy, many infected cells with cytoplasmic AL complex antigen were shown to have a normal nuclear morphology indistinguishable from uninfected cells. Initiation of AL complex infection was interpreted as occurring by transfer of transmissible factor(s) from cell to cell by contact and mutiplication of such factor(s) therein.

Chick embryos were susceptible to AL complex infection following allantoic or amniotic inoculations. Antigen and infectious AL complex were demonstrable in the liver, brain, intestines, lungs, and embryonic membranes. Further investigations on AL complex and its relation to human disease are suggested.
NUCLEAR FLUORESCENCE EMPLOYING ANTINUCLEOSIDE IMMUNOGLOBULINS
Authors: Klein William J. , Beiser Sam M. , Erlanger Bernard F.
Published: June 2004

Fluoresceinated antinucleoside globulins were shown to react with the nuclei of L cells. The pattern of nuclear fluorescence was similar to the distribution of nuclear DNA. This reaction was shown to be specific by the following control experiments:

1. Absorption of the specific antibody from an antiadenosine globulin eliminated all fluorescence.

2. Treatment of the cells with nonfluorescent antiadenosine globulin, followed by staining with the fluorescent antiadenosine eliminated almost all of the fluorescence of the nucleus.

3. Treatment of the cells with DNase destroyed the ability of the nucleus to react with antiuridine fluorescent antibodies.

4. Fluoresceinated anti-BSA did not produce nuclear fluorescence.

Nuclear fluorescence occurred only in cells harvested during the period of maximum DNA synthesis as measured by the uptake of thymidine. This correlates with the previously demonstrated specificity of the antibodies for denatured DNA.
QUANTITATIVE STUDIES OF THE ADOPTIVE IMMUNOLOGICAL MEMORY IN MICE
Authors: Celada Franco
Published: June 2004

A calibrated cell transfer system allows detection of the anamnestic response to albumin without interference from the host's immune machinery; it was used to study the immunological memory of mouse spleen cell populations. The secondary antibody-forming capacity of the transferred cells was measured by challenging them at periods up to 6 months after transfer. The peak levels attained show a declining pattern in two phases: during the first month with a half-life of 15 days; thereafter, with a half-life of 100 days. The corresponding half-lives of the cellular memory are 26 and 190 days.

In the light of these and of radioinactivation data, immunological memory is defined as the persistence of a specifically determined stem cell line, along which the information necessary to give rise to an antibody-forming cell population is transmitted from mother to daughter cells.
THE REGULATION OF PINOCYTOSIS IN MOUSE MACROPHAGES
Authors: Cohn Zanvil A. , Parks Eileen
Published: June 2004

The pinocytosis-inducing effect of a number of molecular species was studied in cultures of mouse macrophages. Agents were added to a basal medium containing 1% NBCS-No. 199 and allowed to interact with cells for 150 min. Vesicle counts were then performed and compared to control cells in the basal medium.

Certain proteins, i.e. albumin and fetuin, with isoelectric points of five and below were found to be potent stimulators of vesicle formation. Basic proteins including lysozyme, histone, and protamine had little influence at sublethal concentrations. The pinocytosis-stimulating activity of bovine plasma albumin could be markedly depressed by removal of bound fatty acids. The addition of either oleic or linoleic acid to de-fatted albumin restored its inducing properties to initial levels. The activity of fetuin could be abolished by either mild acid hydrolysis or neuraminidase digestion. Both procedures removed the majority of the sialic acid content of fetuin.

The D and L isomers of polyglutamic acid were found to produce a marked increase in pinosome production. In contrast, poly-DL-lysine was not effective.

Neutral and basic amino acids were without significant effect on pinocytosis, whereas aspartic and glutamic acids were stimulatory. The amides of glutamic and aspartic acid did not induce pinocytosis. The unnatural D isomers of glutamic, aspartic, leucine, and phenylalanine inhibited pinocytosis. The inhibition by D-glutamic acid could be reversed with the L isomer.

A number of acid mucopolysaccharides, including heparin, hyaluronic acid, and chondroitin sulfate, were excellent inducers. High molecular weight dextran was without significant stimulatory effect whereas dextran sulfate was very active.

Both desoxyribonucleic acid and ribonucleic acid enhanced pinosome formation.

A number of low molecular weight anions including N-acetylneuraminic acid were found to enhance vesicle formation.

In general, anionic molecules were better inducers than either neutral or cationic species. The minimum effective dose of macroanions was a function of molecular weight and their activity appeared unrelated to specific chemical groupings.
STUDIES ON THE MECHANISM OF ACTION OF RILEY VIRUS
Authors: Mahy B. W. J. , Rowson K. E. K. , Parr C. W.
Published: June 2004

The plasma clearance of intravenously injected rabbit muscle LDH was studied. In normal mice the clearance followed a biphasic exponential curve comprising an initial fast and subsequent slow phase. Riley virus-infected mice showed only the slow phase of enzyme clearance. The change from fast to slow clearance rate in normal mice appeared to depend upon the level of plasma enzyme activity rather than on the amount of enzyme cleared.

Treatment of mice with RES-blocking agents (cholesterol oleate and carbon) inhibited the fast clearance phase, whereas an RES-stimulating agent (stilbestrol) caused an accelerated rate of enzyme clearance.

Riley virus infection was found to inhibit the clearance of phosphoglucose isomerase, but had no effect on the clearance of alanine transaminase. The activity of the former enzyme is raised in the plasma of infected mice, whereas the activity of the latter enzyme is unaltered.
THE CONVERSION OF C'1S TO C'1 ESTERASE BY PLASMIN AND TRYPSIN
Authors: Ratnoff Oscar D. , Naff George B.
Published: June 2004

The formation of C'1 esterase from C'1, the first component of complement, may be brought about by the action of plasmin or trypsin upon C'1s, a subcomponent of C'1. These enzymes also decrease the esterolytic activity of C'1 esterase. The formation of C'1 esterase was demonstrated by measuring the appearance of an agent or agents with esterolytic properties and the capacity to inactivate C'2 and C'4, attributes of C'1 esterase. The activity of the agent which evolved was blocked by serum inhibitor of C'1 esterase. The implications of these observations, that the formation of C'1 esterase during complement fixation is mediated by proteolytic processes, are under study. The possible inhibition of C'1q by soybean trypsin inhibitor is in agreement with this hypothesis.
TYPE-SPECIFIC POLYSACCHARIDE ANTIGENS OF GROUP B STREPTOCOCCI
Authors: Freimer Earl H.
Published: June 2004

The type-specific antigen of Group B Type II streptococci has been prepared free of other known cell components. This antigen is a capsular polysaccharide containing D-galactose, D-glucose, N-acetyl-D-glucosamine, and a labile component which has not been chemically characterized. Extraction of Type II streptococci with cold TCA yielded this antigen which contained two serological determinants. A partial antigen with only one of the determinants was obtained by extraction with dilute HCl at 100°C.

By means of the quantitative precipitin inhibition technique, a (ß-D-galactopyranoside has been established as the determinant of the HCl-extracted polysaccharide. The second determinant, present solely in the TCA antigen, has not been identified.
STUDIES OF THE ACTIVITY OF DIPHTHERIA TOXIN
Authors: Duncan J. L. , Groman N. B.
Published: June 2004

It has been demonstrated that a saturating dose of diphtheria toxin produced a 90% inhibition of polio-virus replication in HeLa cells. This inhibition was reflected in infectious viral RNA synthesis and in mature virus production. Toxin had no direct effect on virus particles or I-RNA, and poliovirus adsorption and eclipse appeared to be carried out normally in intoxicated cells.

When toxin was given at various time intervals after infection, the amount of inhibition depended on the time of toxin addition. Toxin given before or immediately after infection gave maximum inhibition, while toxin given several hours after infection had little effect. The data suggest that toxin inhibits viral replication through its effect on protein synthesis. It is likely that a critical step in the viral replication cycle, the production of poliovirus-induced RNA polymerase, is inhibited, and possibly the synthesis of capsid protein.

Ammonium salts and the aliphatic amines, glycamine and prolamine, prevented the inhibition of viral replication by toxin. The kinetics of the protective action of ammonium chloride and diphtheria antitoxin are remarkably similar.
HEMOPOIEITC SPLEEN COLONY STUDIES
Authors: Curry J. L. , Trentin J, J. , Wolf N.
Published: June 2004

The polycythemic repression of erythropoiesis and the restoration of erythropoiesis by specific stimulation were studied in the spleen colony system in irradiated mice.

1. A 5 day period of erythropoietin stimulation (exogenous erythropoietin) or repression (polycythemia) of the bone marrow donor only, does not significantly alter the number or type of colonies formed by the transplanted marrow cells.

2. Erythropoietin stimulation did not alter the number or type of endogenous colonies formed in mice receiving 580 R. Erythropoietin repression (polycythemia) markedly reduced the growth but not the number of erythroid colonies, while not affecting the other types of colonies formed endogenously.

3. Erythropoietin stimulation of the irradiated recipient during colony growth did not alter the number or type of spleen colonies formed by transplanted marrow. Erythropoietin repression by polycythemia during colony growth completely suppressed the appearance of morphologically erythroid colonies without significantly altering the incidence of the other colony types. This effect of polycythemia was completely prevented by exogenous erythropoietin. Irradiated mice are therefore presumed to be secreting sufficient erythropoietin for maximal erythroid colony development.

4. The erythroid colonies suppressed by polycythemia were recognizable as microscopic foci of undifferentiated cells. Exposure of these foci to erythropoietin stimulation at different periods in their development was manifested by different degrees of growth and differentiation, from which it is apparent that erythropoietin stimulates not only morphological differentiation but also rapid mitosis.

Retransplantation of either erythroid or of neutrophilic primary spleen colonies gave rise to both erythroid and neutrophilic secondary spleen colonies. The percentage of erythroid secondary colonies was slightly but significantly higher among the progeny of transplanted erythroid primary colonies than among the progeny of transplanted neutrophilic primary colonies.

On the basis of these and other results, a working hypothesis is proposed for factors controlling the growth and differentiation of spleen colonies from transplanted bone marrow. It is postulated that most but perhaps not all spleen colony-forming units are pluripotent hemopoietic stem cells. It is further postulated that hemopoietic-inductive microenvironments (HIM) of different kinds exist in both the spleen and the bone marrow, and that these determine the differentiation of pluripotent stem cells into each of the lines of hemopoietic differentiation. Erythropoietin therefore may "induce" erythroid differentiation of only those stem cells under the influence of an erythroid HIM. Alternatively erythropoietin may act only as a growth and function stimulant of those stem cells that have been "induced" by an erythroid HIM into a state of erythropoietin responsiveness. In the latter case morphological differentiation presumably results from the functional activity stimulated by ESF.
PRIMARY ANTIBODY RESPONSE IN VITRO IN PERITONEAL CELLS
Authors: Bussard Alain E. , Lurie Melvyn
Published: June 2004

Peritoneal cells (PC), from nonimmunized mice, incubated in a carboxymethyl cellulose gum containing sheep red blood cells (SRBC) and guinea pig complement (following the technique of Ingraham and Bussard) start to produce plaques of hemolysis 20 hr after the beginning of incubation at 37°C.

In contrast, spleen cells from immunized mice complete their plaque-forming activity in 6 hr. The fact that formation of plaques by previously uncommitted cells is related to the life of the leukocytes, and is complement dependent brings evidence that we are dealing with an immunological phenomenon. Puromycin suppresses the formation of plaque. Previous incubation of the PC with SRBC in liquid medium, before incorporation in the detection system, reduces the lag in the production of plaques. This indicates that a phase of stimulation precedes the phase of expression (manifested by plaque formation).

The immunological activity of the peritoneal cell suspension is highly dependent on the concentration of the suspension, which indicates that this activity results from a cooperative process. Actinomycin D, which does not suppress the production of plaques by cells from immunized animals, stops completely the in vitro induction. It is concluded that we have probably observed a primary immune response induced in vitro.
PHYLOGENY OF IMMUNOGLOBULIN STRUCTURE AND FUNCTION
Authors: Clem L. W. , Small P. A.
Published: June 2004

Lemon sharks immunized with bovine serum albumin produced two molecular forms of antibodies detectable by passive hemagglutination of antigen-coated, tanned sheep erythrocytes. Throughout the course of immunization 2-ME-sensitive antibody was associated with a 19S immunoglobulin fraction (4–5 mg/ml serum) while late in the course of immunization antibody was found also associated with a 7S immunoglobulin fraction (7–8 mg/ml serum). No evidence for any anamnestic response was found in these animals. Naturally occurring hemagglutinins for sheep erythrocytes were found to be 2-ME-sensitive and present in the 19S immunoglobulin fraction.

These immunoglobulin fractions were readily purified by DEAE-cellulose chromatography and Sephadex G-200 gel filtration. Both immunoglobulin molecules yielded equimolar amounts of H and L polypeptide chains when subjected to extensive reduction and alkylation followed by gel filtration in 5 M guanidine-HCl. Antigenically reactive H and L chains were obtained by partial reduction and alkylation followed by gel filtration in 1 M propionic acid. The 7S and 19S immunoglobulin H chains were indistinguishable by fingerprints of tryptic digests, disc electrophoretic patterns, antigenic properties, and mass (molecular weight ∼70,000), thus suggesting these two molecules to belong to the same immunoglobulin class. The shark 19S and 7S immunoglobulin L chains were indistinguishable from each other by similar criteria and were different from the H chains. These L chains exhibited the electrophoretic heterogeneity of their mammalian counterparts.

The 7S (shark immunoglobulin) molecule was shown to have a molecular weight of ∼160,000 and to consist of 2H and 2L polypeptide chains (total mass ≅180,000). The 19S molecule was shown to have a molecular weight of 800,000–900,000; therefore, there were probably five 7S subunits per 19S molecule, comparable to mammalian γM. Other reasons for considering the 7S and the 19S lemon shark molecules to belong to a class of immunoglobulins comparable to the γM class of mammals are that they both have high carbohydrate contents, and H chains of mass similar to µ chains.

The lemon shark serum proteins with electrophoretic mobilities comparable to gamma G of mammals were not related to the immunoglobulins of this species. These proteins had no antibody activity and had no antigenic or chemical similarity to either the H chains, the L chains, or the intact immunoglobulin molecules from the lemon shark.
PARTIAL BIOCHEMICAL CHARACTERIZATION OF THE ACTIVATED ESTERASE REQUIRED IN THE COMPLEMENT-DEPENDENT CHEMOTAXIS OF RABBIT POLYMORPHONUCLEAR LEUKOCYTES
Authors: Becker Elmer L. , Ward Peter A.
Published: June 2004

It was shown in the preceding paper that incubation of the rabbit polymorphonuclearleukocyteswith phosphonate esters leads to an irreversible inhibition of the ability of the leukocyte to respond to the chemotactic factor. This "cell-dependent inhibition" was attributed to the inactivation by the phosphonates of an esterase existing in or on the leukocyte in an already activated state. As shown in this paper, incubating the leukocyte with phosphonate in the presence of certain esters prevents this cell-dependent inhibition. The protection is specific; the ester must be an acetate. Ethyl formate, ethyl propionate, ethyl butyrate, glucose 6-phosphate, fructose 1,6-diphosphate, ATP, tosyl arginine methyl ester, or acetyl tyrosine ethyl ester do not protect. The protection is independent of the phosphonate used to inhibit, and the degree of protection depends on the relative concentrations of acetate and phosphonate. Those acetates which protect are also the esters which inhibit chemotaxis when added to the leukocyte in the upper part of the chemotaxis chamber. It is concluded that the activated esterase is an enzyme capable of specifically splitting, or binding acetates, or doing both. Presumably the esterase is some type of acetylesterase or acetylase. The known aliesterase present in the leukocyte is not the activated esterase. Inhibition of the activated esterase by phosphonates has no effect on endogenous or exogenous glycolysis.
THE REGULATION OF PINOCYTOSIS IN MOUSE MACROPHAGES
Authors: Cohn Zanvil A. , Parks Eileen
Published: June 2004

Bovine sera contain factors which are capable of agglutinating mouse erythrocytes and stimulating the pinocytic activity of cultivated mouse macrophages. The hemagglutinating and vesicle-inducing activities of sera increase with the age of the animal and are absent in fetal calf serum.

The majority of this material is recovered in globulin fractions prepared with Na2SO4-(NH4)2SO4 and is absent in bovine fraction II. It behaves as a macroglobulin in studies employing zone electrophoresis, Sephadex G-200 filtration, sucrose density gradient centrifugation, and in its sensitivity to 2-mercaptoethanol and heat.

Absorption of bovine sera with either mouse erythrocytes or spleen cells removes the hemagglutinating and pinosome-inducing properties of the sera.

The addition of small quantities of bovine macroglobulin to mouse macrophages results in a stimulation of pinocytic activity, phase-dense granule formation and the cellular content of three acid hydrolases.

In the presence of heat-labile factors, the macroglobulin initiates the hemolysis of mouse erythrocytes and the cytolysis of mouse macrophages.

This material is thought to represent an interspecies γM-type antibody directed against common antigenic determinants on the mouse erythrocyte and macrophage surface.
PRIMARY IMMUNE RESPONSE IN GRAFTED CELLS
Authors: Nisbet Norman W. , Simonsen Morten
Published: June 2004

The primary immune response elicited by host antigens in a grafted population of immunologically competent cells has been compared in conditions where the same dose of parental cells were grafted simultaneously to F1 hybrid embryos of 13 or 17 days of age. The enlarged chimeric spleens harvested 4 days later were analyzed for donor cell proliferation by using the sex chromosomes as karyological markers, and for proliferation of immunological activity by means of transfer to secondary hosts of the same genotype.

Whereas the total number of dividing donor cells were on the average 16 times higher in 17-day than in 13-day hosts, the recovery of immunological reactivity showed a 6- to 7-fold difference in the opposite direction.

The experiments cast doubt on the proposition that cellular proliferation is necessary for development of a primary immune response. They suggest that there exists an alternative way in which a primary immune response may unfold from involving a few to involving a much larger number of cells.
THE INFLUENCE OF ANTIBODIES ON IMMUNOLOGIC RESPONSES
Authors: Pearlman David S.
Published: June 2004

The influence of antibody on antibody formation to particulate antigen was examined in the rabbit with special reference to the importance of immunoglobulin type, the amount and relative proportion of antigen and antibody involved, and the specificity of this influence. 19S as well as 7S antibody was shown to be an effective inhibitor of antibody formation, although there was some evidence that 7S antibody was the more efficient of the two in doing so. The inhibitory effect of antibody was found to be specific for homologous antigenic determinants. Both 19S and 7S antibody were also able to enhance antibody formation. In contrast to the suppressive phenomenon, however, enhancement appeared to be nonspecific since antibody reactive with homologous (sheep red blood cell) determinants could enhance the response not only to homologous determinants but to heterologous (dinitrobenzene) determinants conjugated to the red blood cells as well. Smaller amounts of antibody were needed to enhance than to suppress antibody formation, and suppression and enhancement depended to some extent on the amount of antigen as well as to the amount of antibody used. The enhancing and suppressing influence of antibody on antibody formation appeared to be exerted concomitantly, for the response to some antigenic determinants was sometimes suppressed at the same time that the response to others was enhanced. It is suggested that enhancement or suppression of immunologic responses by antibody represents a different balance of at least two competing factors operating together: specific neutralization of appropriate determinants thus decreasing the total effective concentration of these determinants available to stimulate the formation of antibodies, and a nonspecific increase in the availability of antigen to immunologically competent cells.
STUDIES ON THE CONTROL OF ANTIBODY SYNTHESIS
Authors: Brody Neil I. , Walker J. Geoffrey , Siskind Gregory W.
Published: June 2004

In the system studied, antigenic competition between two haptenic determinants was found to be of the same extent whether the haptens were on the same or on separate carrier molecules. Suppression of antibody formation to one determinant by administration of passive antibody partially eliminated the depressive effects of antigenic competition when the two haptens were located on separate carrier molecules but had no effect on antibody production to the second hapten when the two determinants were present on the same molecule. The results are discussed in terms of the mechanisms of suppression, antigenic competition, and control of antibody formation.
A PLASMIN-SPLIT FRAGMENT OF C'3 AS A NEW CHEMOTACTIC FACTOR
Authors: Ward Peter A.
Published: June 2004

When streptokinase and highly purified human plasminogen are added to human serum or to partly purified or highly purified preparations containing the third component of complement (C'3), either rabbit or human, a chemotactic factor is generated. This chemotactic factor is a split product of C'3 and is dialyzable, fast moving electrophoretically, slowly sedimenting in sucrose density gradient ultracentrifugation, and has an approximate molecular weight of 6000. It is calculated that this fragment accounts for approximately 4% of the intact molecule.

The C'3 fragment has the following biologic properties: It is chemotactic for rabbit PMN's in vitro, it causes accumulation of PMN's in vivo, and it increases vascular permeability in rat skin.

In addition to generating a chemotactic factor, plasmin destroys the complement-associated chemotactic factor that is a trimolecular complex consisting of the fifth (C'5), sixth (C'6), and seventh (C'7) components of complement. This has been shown by a loss of chemotactic activity, as well as a dissociation of the C'5, C'6, C'7 complex and a destruction of C'6 hemolytic activity.

The biologic significance of the plasmin-generated chemotactic factor is discussed in relation to other recently discovered biologically active fragments of C'3.
THYMUS CELL MIGRATION
Authors: Weissman Irving L.
Published: June 2004

The preceding studies have established the following points: Intrathymic labeling of thymic lymphocytes provides an adequate marker system to detect the migration of thymus cells to peripheral lymphoid sites. In the newborn, this comprises a major portion of the total lymphocyte population in lymph nodes and spleen. In the adult, this migration is limited to specific portions of lymph nodes and spleen, i.e., those portions which serve the recirculating pool of small lymphocytes. Kinetic studies of labeling within the adult thymus indicate that large cells give rise to medium and small cells, which then migrate to the specific sites noted above. In the newborn, the kinetic pattern is similar to that of adults, with the single distinction that large cells also migrate, accelerating the tempo of migration in these hosts. The long-term fate and function of thymus cell migrants has not yet been determined.