bluuebunny/crossref_metadata_2025 huggingface dataset:
CHARACTERIZATION OF A CR51-LABELED ENDOTOXIN AND ITS IDENTIFICATION IN PLASMA AND URINE AFTER PARENTERAL ADMINISTRATION
Authors: Chedid Louis , Skarnes Robert C. , Parant Monique
Published: June 2004

The incubation of endotoxin with Na2Cr51O4 yielded a product which was well labeled. That the label was fixed on the endotoxin itself was shown by autoradiography on specific lines of precipitation formed in agar. Ultracentrifugation at 40,000 RPM sedimented 80 per cent of the total weight of the starting Boivin preparation. Agar diffusion patterns with subsequent autoradiographs demonstrated that the chromium tag was associated only with the heavy fractions of the pellet. The supernatant contained precipitable, but unlabeled endotoxin. Toxicity measurements showed that more than 99 per cent of the total toxicity resided in the pellet fractions.

The chromate-tagged endotoxin was specifically identified in plasma samples taken up to 6 hours after intravenous administration of LD50 or sublethal doses. The endotoxin was not totally detoxified in vivo since plasma collected 6 hours after the injection of even the sublethal dose was toxic when assayed in adrenalectomized mice. The endotoxin was specifically identified in urine specimens but it was no longer toxic or radioactive. Agar diffusion experiments indicated that only degraded material was present.
STUDIES ON THE MECHANISM OF THE LONG CHAIN PHENOMENON OF GROUP A STREPTOCOCCI
Authors: Hahn Jerome J. , Cole Roger M.
Published: June 2004

The formation and destruction of long chains by growth of Group A streptococci in the presence of type-specific antibody have been studied with the fluorescent antibody technique. Long chain formation has been shown to depend on the presence of free antibody during the growth of the bacteria. Destruction of long chains has been shown to depend on the continued growth and division of the bacteria in the absence of free antibody.

Univalent antibody fragments formed by proteolytic digestion of antibody globulin have been shown to have the combining properties of untreated antibody but do not result in the production of long chains.

A model involving end-to-end agglutination during growth of Group A streptococci has been presented to explain the mechanism of production of long chains by growth of Group A streptococci in the presence of type-specific antibody.
MECHANISMS OF ENDOTOXIN TOLERANCE
Authors: Greisman Sheldon E. , Carozza Frank A. , Hills J. Dixon
Published: June 2004

Pyrogenic tolerance following 7 daily intravenous injections of 2.0 µg/kg E. coli endotoxin in albino rabbits was associated with significant increases in RES phagocytic activity as measured with colloidal carbon. Nevertheless, 4 hours after RES blockade with thorotrast (3 ml/kg), the tolerant rabbits exhibited significantly lower fever indices following intravenous endotoxin challenge than did non-tolerant control animals despite comparably depressed capacities to clear carbon from the blood. Moreover, plasma from rabbits tolerant to endotoxin induced significant tolerance in normal rabbits prepared by thorotrast blockade without enhancing the depressed carbon clearance. This passive protection extended to heterologous endotoxins.

Analysis of the data indicates that RES blockade does not abolish tolerance; rather blockade resets the reactivity to endotoxin in the normal and tolerant animal, rendering both exquisitely reactive, but permitting retention of the major portion of tolerance. Apparently the tolerant animal possesses a dual endotoxin defense system. One system is abolished by thorotrast; the other is in part humoral, accounts for the greater portion of tolerance, and is thorotrast-resistant. The nature of the humoral component is not defined but is consistent with that of an opsonin with high endotoxin specificity.
ENHANCEMENT OF ANTIBODY FORMATION BY WHOLE BODY X-RADIATION
Authors: Dixon Frank J. , McConahey Patricia J.
Published: June 2004

Enhancement and acceleration of the antibody response can be achieved in some situations with large, cytotoxic doses of whole body x-radiation given after antigenic stimulation. The timing of radiation is critical and varies with the kind and physical form of the antigen.

It is postulated that the x-radiation depletes the cells of the lymphoid tissues just prior to the rapid proliferation of the antigen stimulated cells. In this situation those surviving cells which are stimulated by antigen multiply more rapidly than their non-stimulated counterparts and disproportionately repopulate the depleted lymphoid tissues. Whether the x-radiation produces other effects contributing to the multiplication of the antibody forming cells was not determined.

It appears that x-radiation produces its enhancement of antibody formation by means different from those operating in endotoxin and colchicine induced enhancement.
AN ASSAY OF GRAFT-HOST INTERACTIONS ACROSS STRONG AND WEAK HISTOCOMPATIBILITY BARRIERS IN MICE
Authors: Miller Joshua , Pierce James C. , Martinez Carlos , Good Robert A.
Published: June 2004

1. A new assay of graft-host interactions has been presented. It consists of the early finding of liver infiltrates in responsive and unresponsive homologous recipients 1 to 3 days after the intravenous injection of competent lymphoid tissue in the mouse.

2. Evidence is presented that infiltrates are of donor origin, and are influenced by a homologous antigenic environment. They can be quantitatively increased by preimmunization of donor to recipient and decreased by preimmunization of recipient to donor. Furthermore, they are present in lethally x-irradiated or neonatally thymectomized unresponsive recipients after intravenous injection of competent homologous spleen cells.

3. Splenomegaly, which also occurs in this early period, is a product of both donor and host-specific immune reactivity together with a small non-specific component of host reactivity.

4. A comparison, of the responsiveness of lymphoid tissue from different strains to the same transplantation antigens is presented, together with the observation of differences in the reactivity of reciprocal donor-recipient injection combinations to each other.

5. Graft-host interactions with this model can be demonstrated in donor-host strain combinations isogenic at the H-2 locus without preimmunization of the donor. Differences in reactivity of reciprocal donor-recipient combinations of lymphoid tissue injections to each other can be detected in this group as well as in the groups differing at the strong H-2 locus.
EXPERIMENTAL GLOMERULONEPHRITIS
Authors: Hammer Dietrich K. , Dixon Frank J.
Published: June 2004

The primary phase of nephrotoxic serum nephritis produced by rabbit nephrotoxic serum appears to be dependent to a great extent, but not completely, upon the participation of serum complement. On the other hand, duck nephrotoxic serum produces its primary renal injury without detectable utilization of or dependence upon serum complement.

The secondary phase of nephrotoxic serum nephritis appears to be largely or entirely dependent upon the host's antibody response to the heterologous gamma globulin fixed in the glomeruli. No evidence could be obtained for the existence of an autoimmune antikidney response by the host in this experimental model.
IMMUNOCHEMICAL STUDY OF ANTIGENIC SPECIFICITY IN DELAYED HYPERSENSITIVITY
Authors: Leskowitz Sidney
Published: June 2004

Delayed hypersensitivity in guinea pigs was produced by immunization. with a conjugate prepared by coupling diazotized arsanilic acid to polytyrosine. The resulting sensitivity could be demonstrated by skin test with conjugates prepared from a wide variety of tyrosine-containing proteins. Definite but smaller degrees of sensitivity could be induced with conjugates of proteins containing little or no tyrosine. The apparent absence of carrier-specificity is considered to be due to the narrowed range of immunologic response produced by immunization with polytyrosine-azobenzenearsonate.

Injections of the hapten N-acetyltyrosine-azobenzenearsonate was found to suppress completely the delayed reaction attributable to the tyrosine-azobenzenearsonate group. The same hapten was only slightly effective in suppressing reactions in guinea pigs immunized with guinea pig serum albumin-azobenzenearsonate, suggesting that a broader range of specificities is involved with such antigens.

Confirmation of such increased range of specificity attributable to antigenic determinants contributed by the carrier protein was obtained by desensitization studies with N-acetyltyrosine-azobenzenearsonate and guinea pig serum albumin-azobenzoate. While separately these materials produced only a slight decrease in skin reactivity to guinea pig serum albumin-azobenzenearsonate, the combination was found to give almost complete suppression.
CHROMATOGRAPHIC RESOLUTION OF THE FIRST COMPONENT OF HUMAN COMPLEMENT INTO THREE ACTIVITIES
Authors: Lepow I. H. , Naff G. B. , Todd E. W. , Pensky J. , Hinz C. F.
Published: June 2004

A euglobulin fraction of human C'1 has been chromatographically resolved into three distinct activities, designated C'1q, C'1r, and C'1s, in the order of their elution from DEAE cellulose. All three of these activities have been shown to participate in various hemolytic reactions requiring C'1, including the cold phase of the Donath-Landsteiner reaction, and to be necessary for generation of C'1 esterase. C'1q was identical with a previously described serum protein implicated in a very early step of complement action and designated the 11S component on the basis of its sedimentation constant. C'1r could not be related to a known complement activity and has been presented as a new component. C'1s, on the basis of chromatographic evidence, was identified with C'1 proesterase. Methods of assay of these components of C'1 have been presented.

The significance of C'1q, C'1r, and C'1s in generation of C'1 esterase and the central role of this enzyme in reactions involving C'1, C'4, and C'2 have been discussed.
THE ACTION OF ENZYMES FROM CLOSTRIDIUM TERTIUM ON THE I ANTIGENIC DETERMINANT OF HUMAN ERYTHROCYTES
Authors: Marcus Donald M. , Kabat Elvin A. , Rosenfield Richard E.
Published: June 2004

A method was described for the partial purification of beta galactosidase and beta glucosaminidase from Clostridium tertium culture supernatants. Treatment of erythrocytes with preparations containing both enzymes decreases their ability to react with anti-I cold agglutinins, and with Type XIV antipneumococcal horse serum. Erythrocytes of blood group A1 are altered more rapidly and extensively than are group O cells. The enzymatic treatment of stroma results in a decrease in ability to absorb anti-I agglutinins and the release of galactose and N-acetylglucosamine as monosaccharides. The data suggest that these two sugars may be structural units of the erythrocyte I determinant, but no direct evidence is available.
STRUCTURE OF TYPE 5 ADENOVIRUS
Authors: Wilcox Wesley C. , Ginsberg Harold S.
Published: June 2004

Type 5 adenovirus was purified by fluorocarbon (freon 113) treatment followed by banding in a CsCl equilibrium density gradient. This method permitted separation of virus from normal host cell materials and virus-specific soluble antigens. Virus banded in CsCl with a mean bouyant density of 1.3349 gm/cm3. The three virus-specific soluble antigens (group- and type-specific antigens and toxin) banded together with a mean bouyant density of 1.2832 gm/cm3. The group-specific antigen was the predominant antigen of the purified virus particle, whereas the group- and type-specific antigens were present in equal titers in the antigen band. Infectious virus particles were inactivated by prolonged dialysis at pH 10.5. Centrifugation of inactivated virus preparations in a CsCl equilibrium density gradient resulted in separation of virus DNA from specific antigen: the antigens banded with a mean bouyant density of 1.2832 gm/cm3 and the DNA sedimented to the bottom of the tube. The predominant antigen derived from purified virus particles was the group-specific antigen and it was in the same relative proportion to the type-specific antigen as measured in intact particles. The antigens derived from disrupted virus were immunologically identical with the soluble virus antigens present in infected cells.
STRUCTURE OF TYPE 5 ADENOVIRUS
Authors: Wilcox Wesley C. , Ginsberg Harold S. , Anderson Thomas F.
Published: June 2004

Purified type 5 adenovirus was disrupted at pH 10.5 and the capsid shown to be comprised of two characteristic morphological subunits: (a) Hollow, polygonal structures corresponding to the virus capsomeres seen in preparation of purified virus and (b) thread-like strands also identifiable in preparations of purified virus. These structures were compared morphologically with purified preparations of the group- and type-specific soluble antigens characteristically produced in mammalian cells infected with adenoviruses. The group-specific soluble antigen was a homogeneous preparation of hollow, polygonal rods identical with the virus capsomeres. The type-specific soluble antigen corresponded to the thread- or fiber-like components of the purified virus particle. Inspection of disrupted virus preparations confirmed earlier immunological data which indicated that the major virus antigen was the group-specific soluble antigen. These data provide convincing evidence for the hypothesis that the adenovirus-induced soluble antigens represent virus subunits produced in excess.
STUDIES OF TUBERCLE BACILLUS-HISTIOCYTE RELATIONSHIPS
Authors: Fong Jacob , Chin Dennis , Elberg Sanford S.
Published: June 2004

The various cellular components of immune rabbit histiocytes have been analyzed for their ability to induce cellular resistance in normal animals. The results of these investigations have shown that the nuclear and mitochondrial fractions were inactive and that the microsomal and ribosomal fractions were active.

The importance of ribonucleic acid in induction of cellular resistance was established by isolation of an active ribosomal RNA and by demonstration of inactivation of this material with ribonuclease but not with deoxyribonuclease or trypsin.

The possibility that viable bacilli were present in immune ribosomes was tested; the absence of complement-fixing antibodies and of skin reactivity to tuberculin in animals inoculated with ribosomes was considered as partial evidence of absence of living bacilli.
FURTHER STUDIES ON ADOPTIVE TRANSFER OF SENSITIVITY TO SKIN HOMOGRAFTS
Authors: Billingham R. E. , Silvers Willys K. , Wilson Darcy B.
Published: June 2004

Mice or rats that have been rendered tolerant of skin homografts from an alien donor strain furnish the basis of a very sensitive and objective test system for investigating the competence of cellular inocula from specifically immunized isologous donors to transfer sensitivity adoptively.

By means of this test system it has been shown that immunologically "activated" cells, capable of transferring homograft sensitivity, are present in the blood, peritoneal exudates, and regional nodes of animals that have rejected skin homografts. Leucocytes were as effective as regional node cells. Activated cells were first demonstrable in the regional nodes and blood of skin homograft recipients at the same time,—on the 6th postoperative day,—suggesting that these cells must enter the circulation very soon after their formation in the nodes. Moreover, when sensitization was effected by skin homografts, but not by means of splenic cell suspensions inoculated intraperitoneally, activated cells are highly persistent, still being demonstrable in both the blood and the nodes more than a year after sensitization.

The finding that thoracic duct cells, which are almost exclusively lymphocytes, were just as effective as leucocytes or regional nodes in transferring sensitivity in rats formally identifies the cell type responsible for transferring sensitivity in the various tissues tested.

Attempts to transfer sensitivity to homografts in normal mice or tolerant mice by means of larger dosages of activated lymphoid cells sequestered in Millipore chambers inserted intraperitoneally were unsuccessful.

All this, and other evidence presented, lends strength to the thesis that skin homograft immunity is a cell-mediated reaction.
ISOLATION AND DESCRIPTION OF THE FOURTH COMPONENT OF HUMAN COMPLEMENT
Authors: Müller-Eberhard H. J. , Biro C. E.
Published: June 2004

Purification of the activity of the fourth component of human complement resulted in the isolation of a highly homogeneous serum protein. Since this protein has not been recorded previously it was called ß1E-globulin on the basis of its immunoelectrophoretic behavior. C'4 activity and ß1E-globulin were found to have highly similar, if not identical physicochemical characteristics. Moreover, ß1E-globulin was shown to exhibit the specific behavior of C'4 activity in that it is taken up only by cells which contain activated C'1. DFP-inactivated C'1 failed to catalyze uptake of the protein. Treatment with hydrazine which is known to destroy C'4 activity, led to changes in the physicochemical properties of ß1E-globulin and rendered the molecule incapable to combine with C'1-containing cells. The evidence indicates that ß1E-globulin represents the fourth component of human complement.
THE PATHOGENIC ROLE OF FIBRIN DEPOSITION IN THE GLOMERULAR LESIONS OF TOXEMIA OF PREGNANCY
Authors: Vassalli Pierre , Morris Robert H. , McCluskey Robert T.
Published: June 2004

An immunofluorescent study of renal biopsies from patients with toxemia of pregnancy has been performed. It was found that the glomeruli consistently showed bright staining for fibrin within endothelial cells, as well as occasional deposits along the basement membrane. Gamma globulin was only occasionally demonstrable, generally in the form of irregular deposits along the basement membrane. ß1C was absent and albumin was not seen in glomeruli, except sometimes in the form of droplets within epithelial cells.

In biopsies from pregnant patients without toxemia only equivocal staining for fibrin was seen.

On the basis of these observations and other evidence discussed, it is proposed that the accumulation of fibrin in glomeruli reflects a prolonged state of intravascular clotting in toxemia and that the arrest in glomeruli of some form of circulating fibrin constitutes the basic pathogenic mechanism of the glomerular damage in this disease.
THE EFFECT OF POTASSIUM DEFICIENCY ON THE REABSORPTION OF PROTEIN IN THE RENAL TUBULE OF THE RAT
Authors: Morrison Ashton B. , Gardner Kenneth D.
Published: June 2004

Male Wistar rats were made potassium-deficient by feeding a diet low in potassium, while controls were pair-fed the same diet supplemented with potassium. Four weeks later 10 mg of T-1824 was injected into each rat. It was found that the characteristic granules which accumulate in the renal collecting tubule cells as a result of potassium deficiency were colored blue and that a diminished coloration of the convoluted tubule cells of the kidney was present. Quantitative measurements of the renal T-1824 content showed that it was decreased as a result of potassium deficiency. The daily rate of protein excretion was increased by the potassium deficiency. It is concluded that potassium deficiency decreases reabsorption of protein in the convoluted tubules of the kidney and that increased proteinuria thus results. Also, the granules which appear in renal collecting tubule cells as a result of potassium deficiency contain serum protein, which probably enters the cells from the tubular lumen.
STUDIES ON THE LOCALIZATION OF CIRCULATING ANTIGEN-ANTIBODY COMPLEXES AND OTHER MACROMOLECULES IN VESSELS
Authors: Cochrane Charles G.
Published: June 2004

Localization of circulating antigen-antibody complexes in vessels of guinea pigs by means of anaphylactic shock was found to be mediated by histamine that was released at the time of anaphylaxis. The source of the histamine may have been the mast cell as noted in studies employing a direct attack on the mast cells by octylamine. Platelets played apparently little to no role in guinea pigs in the anaphylactic deposition of circulating complexes.

Rat anaphylatoxin was found to cause vascular localization and symptoms of anaphylaxis identical with that brought about by antigen-antibody anaphylaxis. This also was found to be dependent upon the release of histamine.

Antibody against Forssman antigen in the vessel walls of the guinea pigs also led to deposition of circulating complexes. This was found not to be histamine dependent.

The possible role of local increase in vascular permeability in certain experimental disease states in the localization of circulating complexes is discussed.
THE CELLULAR ANTIGENS OF GROUP A STREPTOCOCCI
Authors: Wilson Armine T. , Wiley Grove G.
Published: June 2004

The immunoelectrophoretic characteristics of the known cellular antigens of serotype 17, Group A streptococci have been presented. These include C, M, T, and polyglycerophosphate. In addition, three hitherto undescribed antigens of serotype 17 have been encountered.

The F antigen occurs in most serotype 17 strains, has a faster electrophoretic mobility than M, appears in acid, distilled water, and other extracts of harvested cells, is released from the cells in large quantity into the culture medium during growth when the pH is maintained at 7.3 or over, is probably protein in nature, and may play a minor role in mouse virulence of serotype 17 strains. Its antibodies do not confer bactericidal power on human blood.

The E antigen is serotype-specific and is closely associated with the M antigen. The suggestion is made here that E is a part of the M molecule, acquiring independent electrophoretic mobility when separated from the rest of the M molecule by acid hydrolysis and carrying an antigenic determinant serologically distinct from the determinant on the rest of the M molecule. E can be recognized only by immunoelectrophoresis. Its role, if any, in virulence has not been established.

The third antigen, E4, is a non-serotype-specific antigen found in most serological groups and types of hemolytic streptococci. It is serologically related to polyglycerophosphate, but its chemical nature has not been determined. It appears to be unrelated to virulence.
SEPARATION, CHARACTERIZATION, AND BIOLOGICAL SIGNIFICANCE OF A COMMON ANTIGEN IN ENTEROBACTERIACEAE
Authors: Kunin Calvin M.
Published: June 2004

An antigen common to Enterobacteriaceae and closely associated with endotoxin fractions has been separated by chromatography on DEAE cellulose employing elution with a NaCl gradient. The purified common antigen fails to coat erythrocytes, is poorly, if at all antigenic, it is non-dialyzable and excluded from sephadex G-100 gel. It is composed of polysaccharide and polypeptide. The most important property of this antigen thus far determined appears to be its interference with the specificity of the hemagglutination test commonly employed to measure antibody to O antigen of Enterobacteriaceae. It may also have taxonomic significance in classification of this family of bacteria.
EFFECTS OF BACTERIAL ENDOTOXIN ON WATER INTAKE, FOOD INTAKE, AND BODY TEMPERATURE IN THE ALBINO RAT
Authors: Holmes John E. , Miller Neal E.
Published: June 2004

Intraperitoneal injections of Escherichia coli endotoxin in albino rats produces a decrease in food and water intake and a drop in body temperature.

The drop in temperature and in water intake is probably proportional to the size of the dose.

Using a behavioral test in which animals are trained to press a bar at a steady rate for intermittent food or water reward, it is possible to demonstrate the sudden onset of the toxin effect at 30 to 45 minutes after injection.

In any group of rats, all of whom were presumably exposed to E. coli, three types of response to toxin can be found: (a) Sharp reduction in water intake 30 minutes after injection. (b) Little or no change in intake or rate of working for water reward. (c) Immediate depression of work rate.

These three types of reaction appear related to previous experience with the toxin. The "normal" or "inexperienced" reaction a was seen in animals who had not been given toxin before. The "protected" reaction b, with little or no effect of toxin injection on response rate was frequently found 4 to 5 days after a previous injection. The "susceptible" reaction c was found in three animals after 14 or more days had passed since a previous injection.

Injections of toxin into the lateral hypothalamic region of four animals through implanted cannulae had no effect on the rate of bar pressing for water. Control injections of lidocaine blocked response rate completely for brief periods in three animals.
STREPTOCOCCAL M ANTIGEN LOCATION AND SYNTHESIS, STUDIED BY IMMUNOFLUORESCENCE
Authors: Hahn Jerome J. , Cole Roger M.
Published: June 2004

Streptococcal M protein has been studied directly in the intact streptococcal cell by specific immunofluorescence. By this method, it can be seen to be concentrated in or on the cell wall, but cannot be detected in the capsule. The lack of type-specific (but not group-specific) immunofluorescence after trypsinization; and the inhibition of group-specific immunofluorescence by unlabeled type-specific antibody, are observations most compatible with a location of the M antigen determinants on the cell surface superficial to the group antigen.

M antigen is not "resynthesized" after trypsinization of living cells, but appears anew only at sites of new cell wall growth. A limited amount of such growth, leading sometimes to detectable amounts of M in the gross, can take place in deficient media without detectable increases in optical density of the cell population.
COMPLEMENT AS A MEDIATOR OF INFLAMMATION
Authors: Ratnoff Oscar D. , Lepow Irwin H.
Published: June 2004

Purified preparations of the esterase derived from the first component of complement (C'1 esterase) increased vascular permeability in guinea pig skin, an effect inhibited by triprolidine, an antihistaminic agent, but not by soy bean trypsin inhibitor. The permeability-increasing and esterolytic properties of C'1 esterase were inhibited in parallel by the serum inhibitor of C'1 esterase, diisopropylphosphofluoridate and extremes of temperature and pH. Moreover, the permeability-increasing and esterolytic properties evolved in parallel when C'1 esterase was generated from its subcomponents. How C'1 esterase induces changes in vascular permeability remains unexplained, although the possibility that its action is mediated through a histamine-like agent is attractive.
PROPERTIES OF GUINEA PIG 7S ANTIBODIES
Authors: Kourilsky F. M. , Bloch Kurt J. , Benacerraf B. , Ovary Z.
Published: June 2004

Passive immune lysis of antigen-coated erythrocytes provoked in vitro by guinea pig γ2 antihapten antibodies in the presence of complement, is inhibited by guinea pig γ1 antibodies directed against the same specificity.

This inhibition of the lytic effect of complement-fixing γ2 antibodies is presumably due to the competition for antigen by non-lytic γ1 antibodies.
PRODUCTION OF IMMUNOLOGICAL TOLERANCE IN MICE AFTER REPEATED INJECTIONS OF DISRUPTED SPLEEN CELLS
Authors: Martinez C. , Smith J. M. , Blaese M. , Good R. A.
Published: June 2004

1. Tolerance of male skin isografts has been regularly produced in female mice of the C57B1 strain sublines 1, 4, and 6 during adult life by repeated injection of completely disrupted spleen cells derived from male donors. The tolerant state is long-lasting since such grafts have remained in place more than 9 months.

2. Prolonged survival of homotransplants of skin has regularly been produced in DBA/2 mice during adult life by repeated injections of completely disrupted spleen cells from Balb/C donors. When injections of disrupted spleen cell material are continued over a sufficiently long period, permanent acceptance of the skin homografts may be obtained between these strains.

3. Immunological tolerance across even the strong H-2 histocompatibility barrier was obtained in the neonatal period and during adult life by repeated injection of disrupted spleen cell preparations. The tolerant state has been revealed by both mammary adenocarcinoma and skin homografting across this strong histocompatibility barrier.

4. In contradistinction to the tolerant state produced by injection of intact spleen cells in neonatal animals or during adult life or that produced by parabiotic union, the tolerance produced by repeated injection of disrupted spleen cell preparations cannot be transferred to syngenic neonatal mice with spleen cells of the tolerant animal.

5. The implications of these findings in transplantation biology and in consideration of the basic nature of tolerance are discussed.
THE PARTICULATE HYDROLASES OF MACROPHAGES
Authors: Cohn Zanvil A. , Wiener Edith
Published: June 2004

The influence of phagocytosis on the morphological and biochemical properties of macrophage hydrolase-containing granules has been studied in vitro. Following the uptake of large numbers of heat-killed bacteria, an intracellular rearrangement of hydrolytic enzymes occurred. This was associated with the solubilization of 50 to 60 per cent of the total cell content of acid phosphatase, cathepsin, lysozyme, beta glucuronidase, acid ribonuclease, and acid desoxyribonuclease and with a corresponding decrease in granule-bound enzyme. With more prolonged incubation the majority of the soluble intracellular pool of acid ribonuclease and lysozyme was lost to the extracellular medium. No change in the total content of any of the hydrolases was noted during 180 minutes of incubation in vitro.

The morphological fate of the granules was studied by a histochemical method for acid phosphatase. After the phagocytosis of yeast cell walls there was a disappearance of acid phosphatase-positive granules and an accumulation of reaction product about the ingested particle. Experiments employing macrophages which were supravitally stained with neutral red also demonstrated the loss of neutral red-positive granules and the accumulation of the dye about the yeast cell walls.

These results strongly suggest that lysis of macrophage granules occurs following phagocytosis and that a portion of the granule contents are then resegregated within the newly formed phagocytic vacuole.
PEPSIN DIGESTION OF RABBIT AND SHEEP ANTIBODIES
Authors: Schur Peter H. , Becker Elmer L.
Published: June 2004

7S sheep antibody is similar to 7S rabbit antibody, insofar as it too can be digested with pepsin to yield a 5S fragment still capable of precipitating homologous antigen. The 5S fragment from rabbit as well as sheep antibody is capable of fixing guinea pig complement. However, this fixation differs from the fixation by 7S antibody, since preformed antibody-antigen aggregates containing either sheep or rabbit 5S antibody fix only a maximum of 20 to 40 per cent of the total complement. The portion of complement which is fixable by the 5S preformed aggregates seems to be different from the remainder of the complement. Prior treatment of guinea pig serum with 5S washed preformed aggregates removes that portion of complement fixable by 5S antibody, and will leave the complement remaining unable to be fixed by further addition of 5S immune aggregates. Such absorbed complement, however, is as capable as is unabsorbed complement of being fixed by 7S antibody. The 5S sheep and rabbit antibody fixes the portion of complement which it is capable of fixing, as well as or better than the corresponding 7S antibody fixes the total complement. 5S preformed aggregates are broken down by treatment with cysteine, and their complement-fixing ability is lost.
THE ROLE OF INTESTINAL BACTERIA IN THE RECOVERY FROM WHOLE BODY RADIATION
Authors: Rosoff Chester B.
Published: June 2004

Non-absorbable antibiotics, neomycin sulfate or polymyxin B, prevent death from an otherwise lethal dose of whole body radiation by suppressing the activity of the Gram-negative bacterial flora of the intestinal tract.

The protective effect of such suppression has been evaluated over a range of radiation exposure from 325 to 675 r. Coliform-free animals uniformly survive exposure to 550 r, a dose which is regularly lethal for coliform bearing animals.

When antibiotic treatment is begun within 1 hour after 550 r whole body radiation, survival is the rule. Delay in starting treatment is critical, for the longer the delay, the higher the mortality, even though the stool cultures meanwhile become coliform-free.

When antibiotic is started prior to or immediately after radiation exposure, it must be continued for at least 3 weeks if maximum effectiveness is to be obtained. The shorter the postradiation period of treatment, the greater the mortality. This suggests that the defense systems involved require protection for at least 3 weeks in order to permit return of maximal function.

The non-absorbable intestinal antibiotics are effective only when cultural data demonstrate successful elimination of the coliform flora in the gut.
STUDIES ON ARTIFICIAL ANTIGENS
Authors: Benacerraf Baruj , Ojeda Antonio , Maurer Paul H.
Published: June 2004

An effort was made to immunize guinea pigs with arsanilic acid conjugates of copolymers of D- and L-α-amino acids; ASD-GAT and ASL-GAT. An immune response was observed only in the case of ASL-GAT. Antibodies specific for the arsanilic acid hapten were produced which could also react with ASD-GAT or ASGPA. These findings indicate that the proper metabolism of the antigen may be essential to the induction of the immune response.
STUDIES ON ARTIFICIAL ANTIGENS
Authors: Levine Bernard B. , Ojeda Antonio , Benacerraf Baruj
Published: June 2004

The genetic transmission of the capacity to develop an immune response to hapten-polylysine conjugates was studied in guinea pigs.

82 per cent of the 22 offspring of 8 pairs of responder (guinea pigs which are capable of an immune response) parents were also responders, whereas, none of the 26 offspring of 9 pairs of non-responder parents were responders.

None of 11 strain 13 guinea pigs and 100 per cent of 40 strain 2 guinea pigs were responders.

These findings are consistent with the view that the capacity to respond immunologically to hapten-polylysine conjugates is genetically transmitted as a unigenic Mendelian dominant.
EVOLUTION OF THE IMMUNE RESPONSE
Authors: Papermaster Ben W. , Condie Richard M. , Finstad Joanne , Good Robert A.
Published: June 2004

1. The California hagfish, Eptatretus stoutii, seems to be completely lacking in adaptive immunity: it forms no detectable circulating antibody despite intensive stimulation with a range of antigens; it does not show reactivity to old tuberculin following sensitization with BCG; and gives no evidence of homograft immunity.

2. Studies on the sea lamprey, Petromyzon marinus, have been limited to the response to bacteriophage T2 and hemocyanin in small groups of spawning animals. They suggest that the lamprey may have a low degree of immunologic reactivity.

3. One holostean, the bowfin (Amia calva) and the guitarfish (Rhinobatos productus), an elasmobranch, showed a low level of primary response to phage and hemocyanin. The response is slow and antibody levels low. Both the bowfin and the guitarfish showed a vigorous secondary response to phage, but neither showed much enhancement of reactivity to hemocyanin in the secondary response. The bowfin formed precipitating antibody to hemocyanin, but the guitarfish did not. Both hemagglutinating and precipitating antibody to hemocyanin were also observed in the primary response of the black bass.

4. The bowfin was successfully sensitized to Ascaris antigen, and lesions of the delayed type developed after challenge at varying intervals following sensitization.

5. The horned shark (Heterodontus franciscii) regularly cleared hemocyanin from the circulation after both primary and secondary antigenic stimulation, and regularly formed hemagglutinating antibody, but not precipitating antibody, after both primary and secondary stimulation with this antigen. These animals regularly cleared bacteriophage from the circulation after both the primary and secondary stimulation with bacteriophage T2. Significant but small amounts of antibody were produced in a few animals in the primary response, and larger amounts in the responding animals after secondary antigenic stimulation.

6. Studies by starch gel and immunoelectrophoresis show that the hagfish has no bands with mobilities of mammalian gamma globulins; that the lamprey has a single, relatively faint band of this type; and that multiple gamma bands are characteristic of the holostean, elasmobranchs, and teleosts studied. By this method of study, the bowfin appeared to have substantial amounts of gamma2 globulin.

7. We conclude that adaptive immunity and its cellular and humoral correlates developed in the lowest vertebrates, and that a rising level of immunologic reactivity and an increasingly differentiated and complex immunologic mechanism are observed going up the phylogenetic scale from the hagfish, to the lamprey, to the elasmobranchs, to the holosteans, and finally the teleosts.
INFECTION OF MYCOBACTERIUM SMEGMATIS WITH D29 PHAGE DNA
Authors: Tokunaga Tohru , Sellers Margret I.
Published: June 2004

DNA extracted from D29 mycobacteriophage produced plaques when plated on Mycobacterium smegmatis 607. The host bacterium did not require alternation such as conversion to protoplasts; cells susceptible to infection with intact phage were susceptible to DNA.

The bases found in calf thymus DNA constituted the bases of D29 DNA, adenine being paired with thymine and guanine with cytosine. The dissymmetry ratio (A + T/G + C) was 0.56, and the buoyant density in CsCl was 1.722 with a GC content of 63.77 per cent.

The efficiency of plating of the DNA is very much lower than that of intact D29, and it penetrates the host at a slower rate. As does intact phage, D29 DNA requires calcium ions for productive infection of 607.

D29 DNA is significantly inactivated by incubation with RNAase, but the inactivation probably results from a complexing with the DNA rather than from enzyme hydrolysis.
THE LYMPHOID TISSUES AND IMMUNE RESPONSES OF NEONATALLY THYMECTOMIZED MICE BEARING THYMUS TISSUE IN MILLIPORE DIFFUSION CHAMBERS
Authors: Osoba David , Miller J. F. A. P.
Published: June 2004

Neonatally thymectomized mice were implanted intraperitoneally at 7 days of age with Millipore diffusion chambers containing either embryonic or neonatal thymus tissue. Mice which received either empty diffusion chambers or no further treatment following neonatal thymectomy served as controls. In contrast to these controls, most of the mice implanted with thymus-filled chambers gained weight satisfactorily, did not develop a wasting syndrome, and had the capacity to produce serum antibodies in response to sheep erythrocytes and to reject allogeneic skin grafts. Lymphoid follicles were present in the lymph nodes, spleen, and intestinal tract of the implanted mice but most still showed some diminution in the population of lymphocytes in both blood and tissues. Control thymectomized mice had markedly depleted lymphoid tissues and low peripheral blood lymphocyte levels. The tissue recovered after 1 to 2 months from the diffusion chambers showed only epithelial-reticular cells but no lymphoid cells. It is suggested that a humoral factor produced by the thymus epithelial-reticular complex may be responsible for endowing lymphoid cells with immunological competence.
STUDIES ON THE HETEROLOGOUS IMMUNOGENICITY OF A METHANOL-INSOLUBLE FRACTION OF ATTENUATED TUBERCLE BACILLI (BCG)
Authors: Weiss David W. , Bonhag Rose S. , Parks James A.
Published: June 2004

Small quantities of the non-toxic residue of phenol-killed, acetone-washed, and methanol-extracted tubercle bacilli of the BCG strain conferred a high degree of resistance on mice against otherwise lethal experimental infection with Klebsiella pneumoniae and with a number of other pathogenic bacteria.

The heightened resistance reached a peak within 24 hours after administration of the fraction, but was already discernible immediately thereafter. A period of reduced resistance was not observed. The state of heightened resistance was invariably manifested for at least 10 days, and could frequently still be demonstrated after several weeks or months. The methanol-insoluble fraction was immunogenically active even in experimental circumstances under which living BCG exerted no effect. Its protective effect was more marked in females than in males. The optimum dosage must be determined empirically vis-á-vis the strain of infecting organisms and the experimental parameters of administration and testing.

Administration of the fraction to breeding females reduced the incidence of a naturally occurring endemic pneumonitis among their young, and increased considerably the breeding productivity of the mothers. These effects were manifested as late as 11 months after treatment.
MIXED AGGLUTINATION WITH TISSUE SECTIONS
Authors: Tönder Olav , Milgrom Felix , Witebsky Ernest
Published: June 2004

The mixed agglutination procedure was applied to tissue sections. Microtome sections of bovine tissue were placed on coverglasses, fixed by acetone or formalin, and incubated with various dilutions of rabbit antisera. The binding of antibodies to the tissue sections was detected by the addition of an indicator system composed of sheep erythrocytes sensitized by subagglutinating doses of the corresponding rabbit antiserum, and agglutinated by goat antiserum to rabbit serum. In positive reactions the indicator cells covered the tissue, whereas in negative tests, the erythrocytes detached and the tissue appeared uncovered.

It was demonstrated that the method is capable of detecting both saline-extractable and saline-non-extractable antigens. In addition to species-specific antigens, organ-specific antigens of adrenal and brain were detected. The method was characterized by a very high sensitivity in detecting antibodies.

Its possible application as a tool for investigations on tissue antigens and antibodies was discussed.
THE ENTRY AND DISTRIBUTION OF HERPES VIRUS AND COLLOIDAL GOLD IN HELA CELLS AFTER CONTACT IN SUSPENSION
Authors: Epstein M. A. , Hummeler K. , Berkaloff A.
Published: June 2004

The way in which herpes virus of a well adapted strain penetrates susceptible HeLa cells has been investigated using thin sectioning techniques for electron microscopy. Mature virus particles and cells were mixed together in suspension cultures for 15, 30, 60, or 120 minutes so that the stages in virus uptake could be followed in sequence. The ingestion of particles of colloidal gold by HeLa cells under similar conditions was studied for comparison in parallel experiments.

After 15 minutes' contact, the mature virus was found adsorbed on the surface of the cells but separated from them by a narrow gap in which phosphotungstic acid staining was sometimes able to reveal an extraneous coat which appeared as an amorphous layer on the outer aspect of the plasma membrane. When mixing continued for longer the particles were present in deep invaginations or actual cytoplasmic vacuoles, with their outer layers in various stages of stripping and digestion. The stripped, naked, central portion of the virus was occasionally found in these vacuoles but was more commonly free in the cytoplasmic matrix; the mode of transition between these sites could not be determined. Where contact continued for 2 hours these phenomena were much less frequently observed.

The larger particles of colloidal gold were ingested in the same way as the virus, but smaller ones were taken up in micropinocytosis vesicles. The gold passed through membrane-bounded cytoplasmic spaces to accumulate in vacuoles from which, in contrast to herpes particles, it did not escape.

These findings are discussed, and considered with particular reference to their bearing on the initiation of infection, the uptake and disposal of particles by cells, and the influence on the latter of virus morphology.
INCOMPLETE SIMIAN PAPOVAVIRUS SV40
Authors: Melnick Joseph L. , Stinebaugh Sara E. , Rapp Fred
Published: June 2004

A study was made of the effects of 5-fluorouracil (FU) and 5-fluorodeoxyuridine (FUDR) on the replication of the simian papovavirus SV40 in cercopithecus monkey kidney cells and on the production of virus antigen by these cells. Both drugs markedly suppressed the production of new infectious virus by SV40-infected cells. Synthesis of viral protein was also markedly suppressed by FUDR, but not by FU.

In the presence of FU, infected cells produced large amounts of viral protein which were detected by the fluorescent antibody technique. The antigen was not distributed in a particulate fashion as in untreated cells. Diffuse virus antigen was observed in the nuclei of FU-treated cells, resembling the distribution of antigen near the end of the eclipse period in untreated, infected cultures. This stage of antigen production presumably preceded viral assembly.

Virus particles with or without cores were rarely seen with the electron microscope in infected FU-treated cells, although large numbers of SV40 particles were readily visualized in untreated, infected cells. It appears that at least one antigenic protein of this papovavirus is synthesized abundantly in FU-treated cells, but is not assembled into virus shells in the presence of the inhibitor.
CELLULAR SPECIFICITY IN THE HOMOGRAFT REACTION
Authors: Prendergast Robert A.
Published: June 2004

The present study offers direct evidence that cells from the regional lymph node draining first-set skin homografts in rabbits participate in the lymphoid infiltrate at distant sites of graft rejection. With the use of a newly devised method of injection, adequate amounts of tritiated thymidine could be confined to the reactive regional node, other dividing cells of the host remaining unlabeled. It was thus possible to detect the appearance of this uniquely labeled population of cells at remote test sites on the same animal, obviating the necessity for cell transfer. Under these conditions differential counts of the lymphoid elements failed to show a preponderance of labeled cells in the infiltrate accompanying homologous, compared with unrelated control, graft rejection. These results, together with other recently reported data, suggest that the specificity of the homograft reaction is probably dictated by some humoral factor that acts in concert with recently proliferated lymphoid cells to accomplish graft rejection.
PRODUCTION OF ANTIRENIN TO HOMOLOGOUS RENIN AND ITS EFFECT ON EXPERIMENTAL RENAL HYPERTENSION
Authors: Deodhar Sharad D. , Haas Erwin , Goldblatt Harry
Published: June 2004

1. Procedures are described for the extraction and partial purification of dog renin, on a large scale, as well as for the acetylation of rat, rabbit, and dog renin.

2. Untreated homologous renin was not antigenic in rat, rabbit, or dog, but the acetylation of homologous renin made it antigenic.

3. Immunization of rats, rabbits, and dogs, with acetylated rat, rabbit, and dog renin, respectively, resulted in each case in the development of anti-renin to the homologous, untreated, as well as to the acetylated renin.

4. The progressive development of antirenin as a result of repeated, subcutaneous injections of acetylated dog renin, in a dog with experimental renal hypertension for more than 6 years, was accompanied by a correspondingly progressive fall of the mean arterial blood pressure to the prehypertensive level. This points up the important part played by the renin-angiotensin mechanism in the maintenance of the hypertension, even in the chronic phase of experimental renal hypertension.