bluuebunny/crossref_metadata_2025 huggingface dataset:
PROPERTIES OF ANTIBODIES CYTOPHILIC FOR MACROPHAGES
Authors: Berken Arthur , Benacerraf Baruj
Published: June 2004

Cytophilic activity for macrophages was shown to be a property possessed by most, if not all, of the complement binding 7S γ2-population of guinea pig antibodies. Cytophilic antibodies were also demonstrated in rabbit and mouse antisera to sheep red cells. While each species antibody best sensitized homologous macrophages, cross species sensitization was also observed. The binding site for macrophages resides on the Fc fragment, therefore, on the H chains, and is destroyed by pepsin hydrolysis or reduction and alkylation. The binding reaction is reversible with a high rate of dissociation at 37°C. Cytophilic activity is not complement dependent, and was shown to be that property of opsonizing antibody which provides the receptors that permit the binding of the antibody to the macrophage cell membrane in preparation for phagocytosis.
THE ISOLATION AND SELECTED PROPERTIES OF BLOOD MONOCYTES
Authors: Bennett William E. , Cohn Zanvil A.
Published: June 2004

A technique is described for the quantitative recovery of monocytes from horse blood by means of flotation on dense albumin solutions. Monocytes are concentrated in a surface pellicle along with a few lymphocytes which are then removed when the monocytes adhere to a glass surface.

The in vitro cultivation of homogeneous populations of monocytes results in an increase in (a) cell size, (b) number of mitochondria, and (c) phase-dense granules of the centrosphere. The phase-dense granules are osmiophilic and acid phosphatase positive.

Quantitative biochemical analysis during cultivation have revealed increased levels of cytochrome oxidase, acid phosphatase, arylsulfatase, and BPN hydrolase. In addition, glucose utilization and lactic acid production are stimulated under the same conditions.

The uptake of both bacteria and colloidal gold is stimulated during in vitro cultivation. The phagocytic activity of cultured monocytes may be enhanced by a purified bacterial lipopolysaccharide.

These data are consistant with the in vitro maturation of monocytes to macrophages, a cell with greater metabolic and functional potentional.
THE ROLE OF METHIONINE DEFICIENCY IN POLIOVIRUS REPLICATION IN TISSUE CULTURES
Authors: Mohajer Soussan , Gabliks Janis
Published: June 2004

The role of methionine in poliovirus infection in HeLa and monkey kidney cells was investigated by using the methionine analogue l-ethionine. In the presence of 2.0 x 10–3 and 4.0 x 10–3 moles ethionine, the growth of HeLa and monkey kidney cells was significantly inhibited. Under the same experimental conditions, ethionine had no significant effect on the biosynthesis of two strains of poliovirus (Mahoney and Lansing) in HeLa cells, whereas in primary monkey kidney cells, it markedly inhibited the biosynthesis of the Lansing strain of poliovirus. HeLa cells partly depleted of their intracellular amino acids did not change the rate of viral biosynthesis.

The inhibitory effect of ethionine on cell growth and viral biosynthesis was reversed by addition of an excess of l-methionine.
THYMUS-DEPENDENT AREAS IN THE LYMPHOID ORGANS OF NEONATALLY THYMECTOMIZED MICE
Authors: Parrott Delphine M. V. , de Sousa Maria A. B. , East June
Published: June 2004

Specific areas of lymphocyte depletion, termed thymus-dependent areas, have been delineated in neonatally thymectomized C3H/Bi and F1 (C57BL x C3H/Bi) mice. They occur within the lymphoid follicles of the spleen immediately surrounding the central arterioles, and constitute the mid and deep cortical zones of the lymph nodes. These depleted areas appear in healthy thymectomized mice as early as 3 wk after operation but, in mice which survive for more than 6 to 7 wk, the thymus-dependent areas are repopulated by rapidly dividing pyroninophilic cells, the majority of which are immature plasma cells.

Syngeneic thymus cells, labeled in vitro with tritiated adenosine localize preferentially in the thymus-dependent areas after intravenous injection. Similarly labeled spleen cells also accumulate in these areas but, in addition, are distributed at the periphery of splenic follicles and in the outer cortical zone of the lymph nodes. Many more spleen than thymus cells enter the lymphoid tissues and the spleen appears to be the primary target.

The apparent paradox that syngeneic thymus cells are less efficient than spleen cells in restoring neonatally thymectomized mice to normality is discussed in the light of these results and possible routes by which the migrating cells could enter the lymphoid tissues are considered. The origin of the plasma cells which repopulate the lymphocyte depleted areas is also discussed.

It is concluded that the normal thymus produces cells which contribute directly to the migratory or circulatory lymphocyte population but that there also exists another source of supply for the plasma cell series. These two systems may function synergistically so that the thymus may control, directly or indirectly, the balance of cell populations within the body.
THE REACTION MECHANISM OF ß1C-GLOBULIN (C'3) IN IMMUNE HEMOLYSIS
Authors: Müller-Eberhard Hans J. , Dalmasso Agustin P. , Calcott Mary Ann
Published: June 2004

During immune hemolysis by human complement, C'3 (ß1C-globulin) becomes physically attached to the erythrocyte membrane. Binding of C'3 was found to be mediated by cell-bound, activated C'2 and to have the characteristics of an enzymatic reaction. A single C'4,2a site on the cell surface effected the binding of several hundred molecules of C'3 if the latter was provided in excess. The accumulation of hemolytically inactive, physicochemically altered C'3 in the fluid phase was found to be an inherent feature of the process of C'3 binding. It is postulated that C'4,2a activates C'3 for its subsequent reaction with cell membrane receptors. Antierythrocyte antibody did not play an essential role in C'3 uptake; C'3 could be bound to erythrocyte-C'4,2a complexes which were entirely devoid of antibody.

Cell-bound C'3 proved hemolytically active, the degree of hemolysis being proportional to the number of C'3 molecules per cell. Binding of a large number of C'3 molecules per cell was found to be a prerequisite for the production of the immune adherence phenomenon and for immune hemolysis.
THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION
Authors: Smart K. Marilyn , Kilbourne Edwin D.
Published: June 2004

The initial observations that cortisone may act as an inhibitor of viral interference (11, 4) are now explicable as an inhibitory effect on interferon synthesis. The suggestion that the action of interferon is also inhibited by cortisone or its analogues (6) has not been confirmed in a plaque reduction type of interferon assay system in which autointerference by the challenge inoculum is a lesser problem. In this respect, the present results are in accord with those obtained by DeMaeyer and DeMaeyer (8) with hydrocortisone in a system in which a low multiplicity (0.1) Sindbis virus infection in monolayer culture was employed with cytopathic effect (CPE) as an end-point. It has been shown that hydrocortisone is restrictive to the synthesis of interferon induced by inoculation of either infective or inactivated virus into the chick embryo, and that this inhibitory effect is temporary. However, in another study in the chick embryo, three spaced injections of hydrocortisone (0.25 mg/dose) prevented the appearance of detectable interferon during the entire 64 hr observation period following inoculation of 103.3 EID50 of Lee virus (12).

The importance of explicit definition of experimental conditions in assessing hormonal effects on infection is illustrated by the capacity of hydrocortisone either to inhibit or increase interferon synthesis in vitro, depending on the proportion of inactivated and infective virus in the inoculum employed, and the time at which interferon is measured. As suggested previously, it is not unlikely that similar shifts in hormone-virus-interferon balance may operate in vivo to influence the outcome of infection.
THE STATE OF HEMOGLOBIN IN SICKLED ERYTHROCYTES
Authors: Stetson Chandler A.
Published: June 2004

Electron microscopic and other evidence have provided support for the hypothesis that the sickling phenomenon is due to the intracellular formation of long slender crystals of reduced sickle hemoglobin. The rapid growth of these crystals causing tenting of the cell membrane is responsible for the bizarre distortion of the erythrocytes and presumably for the disease itself.
MICROBIAL PERSISTENCE
Authors: McCune Robert M. , Feldmann Floyd M. , Lambert Harold P. , McDermott Walsh
Published: June 2004

A previously reported form of microbial persistence whereby large populations of tubercle bacilli can be made to "vanish" uniformly from the tissues of mice has been shown to occur generally throughout each group of animals subjected to the experimental procedure; it does not reflect the eradication of the bacilli in the majority of animals with their persistence and ultimate revival in only a minority. The one demonstrable alteration of the tubercle bacilli while "vanished" is that they are sterile. Thus, they are undetectable by cell-free culture, tissue culture, and blind animal passage, i.e. by any method based on microbial multiplication. Whether they have also undergone alteration in morphology and persist in some unconventional form cannot be stated. Acid-fast forms similar to tubercle bacilli can be detected in small numbers by intensified microscopic search of tissue homogenates but the relationship of these forms to the sterile bacilli that ultimately revive is unclear. Thus, the persisting tubercle bacilli are more correctly designated as being in a "sterile state" than one of true latency. The uniform induction of the sterile state is a specific phenomenon requiring the participation of both the nicotinamide derivative, pyrazinamide, and isoniazid. Once assumed, this sterile state is relatively stable and the time required for revival of the tubercle bacilli in the spleens in one-half the animals is seven months. This process can be speeded up by the administration of large doses of cortisone in the third or fourth month after sterilization but revival is not significantly affected by the administration of cortisone earlier.
MICROBIAL PERSISTENCE
Authors: McCune Robert M. , Feldmann Floyd M. , McDermott Walsh
Published: June 2004

The capability of tubercle bacilli to assume a long continued sterile state in the tissues when exposed to pyrazinamide and isoniazid is a highly specific drug-microbe phenomenon in which host participation is not critical. Although it is the pyrazinamide that possesses the sterilizing type of action, the role of the isoniazid is specific and essential. The isoniazid serves to convert a phenomenon that occurs irregularly with pyrazinamide alone into one that occurs with a high degree of uniformity. The observations suggest a competition between isoniazid and the pyrazinamide (or its parent nicotinamide) for a site or entrance in or on the tubercle bacilli and for sterilization, the isoniazid apparently must reach the site first. The rare failures to attain complete sterilization, appear to depend on the emergence of pyrazinamide-resistance which prevents the necessary dependent action of the two drugs. Populations already in the sterile state are nevertheless subject to a continued drug influence. Whether this represents a direct action on the sterile bacilli or an indirect effect produced by making the environment hostile to microbial revival, cannot be determined from the present observations.
THE PRESENCE IN PENICILLIUM FUNICULOSUM OF AN INHIBITOR TO THE ANTIVIRAL AGENT HELENINE
Authors: Cheng Ping-Yao , Shope Richard E.
Published: June 2004

The present findings indicate that the wide fluctuation observed in the antiviral activity of various crude helenine preparations may be attributable to the presence of varying amounts of inhibitor. Antiviral activity could be enhanced by removal of the inhibitor. A meaningful value for helenine titer in a preparation clearly should be determined in the inhibitor-free zone.
RABBIT LYMPHOID CELLS DIFFERENTIATED WITH RESPECT TO α-, γ-, AND µ- HEAVY POLYPEPTIDE CHAINS AND TO ALLOTYPIC MARKERS AA1 AND AA2
Authors: Cebra J. J. , Colberg J. E. , Dray S.
Published: June 2004

Lymphoid cells present in spleen and lymph nodes of hyperimmune rabbits were found to be differentiated with respect to the class of immunoglobulin heavy chain which they contained. The relative proportions of cells containing the various heavy chains were as follows: α-chain (5 to 8%), µ-chain (14 to 21%), and γ-chain (71 to 81%). The allotypic markers Aa1 and Aa2, found on heavy chains, were also found to be separately localized in cells of Aa1/Aa2 heterozygous rabbits. The ratio of cells in spleen and lymph nodes containing the Aa1 marker to those containing the Aa2 marker varied with individual rabbits; the range was 53 to 88% Aa1 versus 12 to 47% Aa2.
STUDIES ON DELAYED CUTANEOUS INFLAMMATORY REACTIONS ELICITED BY INOCULATION OF HOMOLOGOUS CELLS INTO HAMSTERS' SKINS
Authors: Ramseier Hansruedy , Billingham R. E.
Published: June 2004

The intracutaneous inoculation of lymph node cell suspensions from normal hamsters into normal, homologous hosts causes the development of delayed inflammatory reactions, normal lymphocyte transfer (NLT) reactions, the intensities of which reflect the antigenic disparity between donor and recipient. The immunogenetic situations in which they occur indicate that these reactions are due to sensitization in situ on the part of inoculated immunologically competent cells against alien antigens of the host. They are graft versus host reactions. If hamsters are sensitized by cellular or solid tissue homografts and then challenged intracutaneously with lymphoid or epidermal cells from the donor strain, direct reactions are provoked. A positive correlation exists between the development of transplantation immunity and the capacity to give direct reactions. The sensitivity responsible for direct reactions can be suppressed by irradiation or administration of cortisone, and it is transferable by means of viable lymphoid tissues or cells but not by means of serum.

Intracutaneous inoculation of viable node or splenic cells from specifically sensitized hamsters into hosts of the donor strain incites transfer reactions, the intensities of which depend upon the number of cells transferred and the level of sensitivity in the animal that provided them. These reactions are not incitable by thymocytes, by killed lymphoid cells, or by serum. Transfer reactions differ from NLT reactions only on a quantitative and chronologic basis. However, a sharp experimental distinction can be drawn between them. For example, if normal MHA node cells and node cells from MHA hamsters sensitized against CB antigens are injected into the skins of MHA's tolerant of CB tissue, only the sensitized cells incite reactions.

Both direct and transfer reactions are highly specific immunologically. The inability of node cells to incite NLT or transfer reactions in heavily irradiated hosts and other findings sustain the thesis that it is host cells of hematologic origin, rather than indigenous skin cells, that contribute the antigenic stimulus required for these reactions.

All the findings presented are consistent with the hypothesis that the various delayed inflammatory reactions described are manifestations of immunological responses on the part of immunologically competent cells against alien transplantation antigens.
STUDIES ON THE EFFECT OF THE CARRIER MOLECULE ON ANTIHAPTEN ANTIBODY SYNTHESIS
Authors: Paul William E. , Siskind Gregory W. , Benacerraf Baruj
Published: June 2004

Equilibrium measurements of interactions of anti-DNP antibodies, prepared using DNP-PLL and several DNP-proteins for immunization, with DNP0.6-PLL240 and with the univalent hapten, ϵ-DNP-L-lysine, were made utilizing the technique of fluorescence quenching. Carrier specificity of anti-DNP-PLL antibodies was demonstrated by a higher average intrinsic association constant (K0) of anti-DNP-PLL antibodies with DNP0.6-PLL240 than with ϵ-DNP-L-lysine. The free energy contribution of the PLL carrier to the interaction of intact anti-DNP-PLL antibodies with DNP0.6-PLL240 was from –0.8 to –2.1 kcal/mole. On the other hand, intact anti-DNP-protein antibodies displayed a lower energy of interaction with DNP0.6-PLL240 than with ϵ-DNP-L-lysine of up to +2.4 kcal/mole.

Fab' fragments of both anti-DNP-PLL and anti-DNP-BGG antibodies have K0's with ϵ-DNP-L-lysine identical to the K0's of the intact anti-DNP antibodies from which they were prepared. However, K0 of interaction of Fab' fragments with DNP0.6-PLL240 (a large proportion of the conjugated PLL molecules in this preparation bear more than one DNP group) is considerably lower than that of the intact antibody. Thus a cooperative effect in the binding of bivalent antibody and bivalent (or greater) antigen exists and is of the order of –1.2 to –2.0 kcal/mole of IgG antibody.

Although the direct contribution of the carrier to the interaction of Fab' fragment of anti-DNP-PLL and DNP0.6-PLL240 is –0.4 kcal/mole, the energy of carrier specificity, based upon consideration of cooperative effects and of repulsion of anti-DNP-protein antibodies for portions of the DNP-PLL determinants, is of the order of –3 kcal/mole (approximately 30% of total binding energy).
INTERACTION OF DIPHTHERIA TOXIN WITH CELL CULTURES FROM SUSCEPTIBLE AND RESISTANT ANIMALS
Authors: Gabliks Janis , Falconer Marcia
Published: June 2004

The cytotoxicity (TD) level of diphtheria toxin for human Chang liver strain was 0.1 guinea pig MLD per ml; for mouse liver NCTC 1469 strain, the TD was 500 MLD per ml. The results of cell culture toxicity correlated well with relative susceptibility of both man and mouse. The initial effects of toxin on the susceptible Chang liver cells were studied at one half the TD level (0.05 MLD per ml). At this low concentration of toxin, the number of cells per culture was reduced slightly below the "0" hr values, whereas the amounts of cell protein, RNA, and DNA were increased. Analysis of the toxin-treated cells indicated an enlargement of the cells. The individual cells contained significantly more protein, RNA, and DNA than the control cells and the cell volume was increased 1.9 times.

When purified diphtheria toxin was incubated with the susceptible Chang liver cells and then tested for its biological activity, the results showed an increased diffusion rate in parabiotic culture chambers and definite cytotoxicity to the normally resistant mouse liver cells. The cytotoxicity was neutralizable with antitoxin. The results suggest that the toxin-susceptible cells transform the toxin molecule to a more active derivative which affects the highly resistant mouse liver cell.
ANTINUCLEAR ANTIBODIES IN RABBIT ANTISERA
Authors: Barnett Eugene V. , Vaughan John H.
Published: June 2004

Antinuclear antibodies were detected by immunofluorescence in most sera from rabbits immunized with whole human serum emulsified in Freund's complete adjuvant. Four of 14 sera from rabbits immunized with Cohn fractions III, IV-1, or IV-4 also gave positive nuclear fluorescence with human leukocyte nuclei. Other human and animal nuclei gave negative results with these rabbit antisera. Three rabbit anti-whole human sera had complement-fixing antibody against DNA in sufficient titer for study in quantitative complement fixation tests. Antibody with greatest reactivity with human single strand DNA was detected in the 3 rabbit antisera. Reactivity with rabbit, calf thymus, and B. natto DNA was also detected. In each case reactivity was greater with single strand than with native DNA. Antibodies against human histone and purine-6-oly BSA were also detected. No correlation was found between the titers of rheumatoidlike factors and antinuclear antibodies present in the rabbit antisera. The induction of antinuclear antibodies in these rabbits was not associated with disease attributable to the antibodies. The induction of antinuclear antibody by immunization with whole human serum was interpreted as indicating the presence of antigenic nuclear material in whole human serum.
THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION
Authors: Rytel Michael W. , Kilbourne Edwin D.
Published: June 2004

The administration, of 5.0 mg of cortisone 6 to 24 hr prior to the intravenous injection of mice with NDV was associated with a marked reduction in the interferon response as measured in serum and spleen. Reduced concentrations of interferon following cortisone pretreatment were demonstrable from 6 to 16 hr following injection of virus.
EFFECT OF SPLENECTOMY ON THE SUSCEPTIBILITY OF MICE INOCULATED WITH DIPLOCOCCUS PNEUMONIAE
Authors: Shinefield Henry R. , Steinberg Charles R. , Kaye Donald
Published: June 2004

An experimental model is described which demonstrated increased susceptibility of mice to infection with D. pneumoniae following splenectomy. It was necessary to use small numbers of a particular strain of pneumococcus (D. pneumoniae type 6), intravenous infection and a particular strain of mouse (pathogen-free NCS strain). The increase in susceptibility persisted for at least 4 months after splenectomy.

With modifications in experimental design such as use of large numbers of organisms, a different strain of pneumococcus, the intraperitoneal route of infection or a different mouse strain no increase or a much less impressive increase in susceptibility was demonstrated.

Following intravenous injection of small numbers of D. pneumoniae Type 6 bacteremia tended to persist in all NCS mice. Multiplication of pneumococci subsequently occurred in a higher proportion of mice with splenectomy and at a more rapid rate than in control animals. Mice with splenectomy usually had more D. pneumoniae per ml of blood than per gram of any tissue. This suggested that in these mice multiplication of microorganisms occurs primarily in blood. In control mice higher concentrations of bacteria were present in spleen than in blood, and higher concentrations were found in blood than in other tissues. These results suggested that in normal mice infected intravenously with small numbers of D. pneumoniae Type 6, the spleen protects by removing and killing small but critical numbers of D. pneumoniae which are circulating in the blood.

No evidence was found to suggest that the altered susceptibility is mediated by an effect of splenectomy on numbers of circulating leukocytes or on the antibacterial activity of mouse blood.
THE FUNCTIONAL CAPACITY OF HYPERTROPHIED NEPHRONS
Authors: Morrison Ashton B. , Howard Ruth M.
Published: June 2004

A method is described for the measurement of inulin and PAH clearances in rats without killing the animal. Inulin clearance measurements of partially nephrectomized rats and sham-control rats were made before operation and at intervals following the operation; inulin clearances were determined on normal rats at intervals during their growth. In another series of partially nephrectomized rats and their sham-operated controls, inulin and PAH clearances were determined in all the animals before and at intervals following the operation. Glomerular counts were made in some rats.

After partial nephrectomy the inulin clearance is reduced but not as much as would be expected considering the amount of renal tissue removed. The mean inulin clearance per nephron is greatly increased in the partially nephrectomized rat when compared to the value determined for the control rat. The inulin clearance of the partially nephrectomized rat shows a progressive decline which is first clearly evident about 6 months after operation. The sham-operated rats showed an inulin clearance slightly less than that of nonoperated controls about 24 to 30 wk after the operation. In the normal rats the inulin clearance relative to body weight is much greater in rats with a mean weight of 197 ± 3 g than in normals which are older and heavier.

The PAH dearance of the partially nephrectomized rat is reduced following operation but undergoes no further change in the ensuing 24 wk.
THE BEHAVIOR OF HAPTEN-POLY-L-LYSINE CONJUGATES AS COMPLETE ANTIGENS IN GENETIC RESPONDER AND AS HAPTENS IN NONRESPONDER GUINEA PIGS
Authors: Green Ira , Paul William E. , Benacerraf Baruj
Published: June 2004

30 to 40% of Hartley strain guinea pigs have previously been demonstrated to possess a dominant autosomal gene which enables them to recognize the antigenicity of hapten-poly-L-lysine conjugates as expressed by the development of both antihapten antibodies and delayed hypersensitivity to the immunizing antigen. In the present study, it was shown that PLL alone was weakly antigenic in such genetic responder animals. Immunization with DNP-PLL electrostatically combined with foreign albumins elicits the production of anti-DNP antibodies in all Hartley strain guinea pigs, although the percentage of animals demonstrating a delayed response to DNP-PLL and therefore considered genetic responders remains 30 to 40%. Immunization with nonantigenic polyanions combined with DNP-PLL does not produce such an effect. Some degree of PLL specificity of purified anti-DNP antibodies produced by genetic nonresponder animals by immunization with DNP-PLL combined with foreign albumins was demonstrated by means of fluorescence quenching.
ANTIBODY PRODUCTION BY CELLS IN TISSUE CULTURE
Authors: Hannoun Claude , Bussard Alain E.
Published: June 2004

An organ culture technique was used to investigate the migration and the morphological evolution of lymphocytes from lymphopoietic tissues. This evolution was compared with the behavior of cells extracted from the tissue and kept in nutritive medium in vitro. It was found that cells were continuously migrating from the fragments of lymph nodes or spleen, and were attaching to the glass. They spread on glass, their protoplasm enlarged and their nucleus became clearer. The evolution towards blastoid cells was identical with that described under artificial stimulation by PHA for example. Cytological identification of the cells actively engaged in antibody synthesis (as detected by local hemolysis in gum) at the time of staining, showed that several distinct cellular types were active, including plasma cells and macrophagelike cells. It is assumed that the stimulated lymphocytes, after spontaneous migration from the tissue are able to evolve into an "immunoblast" stage and then, eventually after fixation upon a physical support, to initiate antibody synthesis.
IMMUNOCHEMICAL STUDIES ON THE ANTIGENIC DETERMINANTS REQUIRED TO ELICIT DELAYED AND IMMEDIATE HYPERSENSITIVITY REACTIONS
Authors: Schlossman Stuart F. , Ben-Efraim Shlomo , Yaron Arieh , Sober Herbert A.
Published: June 2004

Hartley and strain 2 guinea pigs were sensitized to chemically defined α-DNP(Lys)n-BuAm, α-DNP(Lys)n-, and (Lys)n-BuAm peptides and skin tested with individual members of these homologous series, related peptides and hapten-substituted proteins. The immediate skin response (Arthus) could be elicited with hapten-substituted tetra-, penta-, or hexamers, whereas both immediate and delayed skin responses could be provoked by the octamer or nonamer. The hapten is an integral part of the determinant for both immediate and delayed skin reactivity, since poly-L-lysine was unable to elicit either delayed or immediate reactions in sensitized animals. Arthus type cross-reactions occurred only when the sensitizing and test antigen shared a common haptenic determinant. In contrast to this, in this system, delayed type cross-reactions occurred only when the test antigen and the sensitizing antigen contained both a large oligo-L-lysine carrier as well as the same haptenic determinant.

These observations imply that the mediation of the delayed response requires a larger determinant than is necessary to elicit the immediate response. The role of high affinity antibody as the mediator of the delayed response is discussed in terms of the size of the antigenic determinants required to elicit this response.

It was found that the ability to elicit the delayed response paralleled the immunogenic capacity of these peptides, whereas the immediate response could be elicited by nonimmunogenic peptides. This finding suggests that the delayed response may require the continued biosynthesis of antibody and may be analogous to a local in vivo secondary response.
ELASTIN: DIMINISHED REACTIVITY WITH ALDEHYDE REAGENTS IN COPPER DEFICIENCY AND LATHYRISM
Authors: Miller E. J. , Fullmer Harold M.
Published: June 2004

Elastin fibers in the aortas of control, lathyritic, copper-supplemented, and copper-deficient chicks were examined histochemically and chemically for aldehyde content. Diminished staining for aldehydes was obtained in the fibers from the aortas of lathyritic and copper-deficient chicks. Chemical studies of elastin isolated from the aortas of control and lathyritic chicks showed an apparent loss of lysine residues in control elastin to be associated with an increase in aldehyde content providing evidence that lysine is converted to an aldehyde-containing intermediate during biosynthesis of desmosine and isodesmosine. Approximately 6 aldehyde groups were present for every 1000 amino acids in elastin isolated from the aortas of control animals, while the corresponding number in lathyritic elastin was 4. At least two types of aldehydes, saturated and α,ß-unsaturated, appear to be associated with elastin, suggesting the presence of more than one intermediate between lysine and the desmosines.
ONTOGENY OF THE IMMUNE RESPONSE
Authors: Williams G. M. , Nossal G. J. V.
Published: June 2004

Polymerized flagellin from Salmonella adelaide was labeled with I125 and injected into rats varying in age from 0 to 42 days. Lymphoid organs were removed at various intervals and the progressive development of antigen-capturing structures was studied using autoradiography. The chief findings were as follows:

1. Newborn rats lack the follicular and medullary antigen-trapping structures characteristic of adult animals.

2. At the age of 10 to 14 days, the first signs of specific cortical antigen localization appear in lymph nodes. This initially takes the form of a continuous "cortical rim" of antigen localization.

3. Within a further 4 to 6 days, the Anlagen of true follicular antigen-capturing structures appear, the continuous rim being only a transitional mechanism.

4. The antigen-capturing part of the follicle appears before the lymphoid component; follicle Anlagen can be defined only on autoradiographs and cannot be seen on ordinary histological sections.

5. The system of medullary macrophages develops gradually over the period 2 to 6 weeks of age.

6. The ability of lymph nodes to retain antigen increases progressively, there being a fivefold increase in the amount of antigen retained per unit weight of lymphoid tissue between 2 and 6 wk of age.
INFECTIOUS VIRUS-ANTIBODY COMPLEX IN THE BLOOD OF CHRONICALLY INFECTED MICE
Authors: Notkins Abner Louis , Mahar Suellen , Scheele Christina , Goffman Joel
Published: June 2004

If viremic sera from mice chronically infected with lactic dehydrogenase virus (LDV) were first treated with ether or ultraviolet light to inactivate the infectious virus, neutralizing antibody could be demonstrated. Significant amounts of antibody, however, were not detected until the mice had been infected for about 2½ months and its presence did not result in the elimination of the chronic viremia. Virus isolated from sera containing neutralizing antibody was found to be relatively resistant to neutralization by anti-LDV. Further studies revealed that the resistant virus existed in the form of an infectious virus-antibody complex (sensitized virus). The presence of such a complex was demonstrated by the fact that the virus fraction which persisted after in vivo or in vitro exposure to mouse anti-LDV was readily neutralized by goat anti-mouse sera or goat anti-mouse γ-globulin, whereas virus that had not been previously exposed to mouse anti-LDV was completely resistant to neutralization by goat anti-mouse sera. These findings suggest that (a) sensitization may play an important role in the resistance and susceptibility of a virus to neutralization by antiviral antibody, and (b) an anti-γ-globulin may prove useful in neutralizing the resistant fraction and in demonstrating otherwise undetectable antiviral antibody.
CRYSTAL-INDUCED INFLAMMATION IN CANINE JOINTS
Authors: McCarty Daniel J. , Phelps Paulding , Pyenson Jacob
Published: June 2004

Injection of sodium urate or calcium pyrophosphate crystals into the stifle joints of anesthetized dogs almost invariably induced an acute exudative response. This response was quantified by serial measurements of intra-articular pressure, pH and leukocyte concentration. Pressure rose progressively and reflected intra-articular volume increase. The hydrogen ion concentration increased as the reaction progressed and correlated in a given exudate with the leukocyte concentration.

Analysis of sequential physiologic and biochemical changes occurring in this model of crystal-induced inflammation may provide insight into the mechanisms of acute gouty arthritis in man.
THE INFLUENCE OF ERYTHROPHAGOCYTOSIS ON THE INTERACTION OF MACROPHAGES AND SALMONELLA IN VITRO
Authors: Gill Fred A. , Kaye Donald , Hook Edward W.
Published: June 2004

Phagocytosis and killing of Salmonella typhimurium by mouse peritoneal macrophages was inhibited when the bacteria and antibody-coated homologous erythrocytes or heterologous erythrocytes were simultaneously exposed to macrophages in vitro. No inhibition of phagocytosis or killing was observed in experiments employing uncoated or disrupted antibody-coated homologous erythrocytes.

Degradation of S. typhimurium as measured by the loss of fluorescence from intracellular salmonella coated with fluorescein-labeled antibody was inhibited in macrophages which had previously ingested antibody-coated homologous erythrocytes.

Anti-mouse-erythrocyte serum was found to have a cytotoxic action on mouse macrophages. However, the viability of macrophages was not altered by phagocytosis of antibody-coated homologous erythrocytes or uncoated heterologous erythrocytes.
THE CHEMOSUPPRESSION OF CHEMOTAXIS
Authors: Ward Peter A.
Published: June 2004

The effects of various drugs on chemotaxis of polymorphonuclear leukocytes (PMN's) in vitro and in vivo have been studied. Response of rabbit PMN's in vitro to the chemotactic factor of rabbit serum, consisting of an activated protein-protein complex of the fifth and sixth (and probably seventh) components of complement (C'), is suppressed by hydrocortisone, methyl prednisolone, and chloroquine. Drug concentrations causing 50% inhibition of chemotaxis in vitro were found to be: hydrocortisone, 2.9 x 10–4 M; methly prednisolone, 1.2 x 10–4 M; and chloroquine 8.5 x 10–6 M. The hydrocortisone effect on PMN's appeared to be irreversible, since washing of the cells did not restore their chemotactic response. 2, 4-Dinitrophenol (DNP), vitamin A, and endotoxin did not inhibit chemotaxis. Hydrocortisone and chloroquine did block serum C' activity in vitro, but only at substantially higher concentrations.

Using the reversed passive Arthus reaction in guinea pigs as a model for chemotaxis in vivo, systemic treatment of animals with hydrocortisone or chloroquine inhibited development of the vasculitis. Circulating antigen and C' were fixed in vascular structures, and serum C' was not perceptibly altered. Nevertheless, PMN infiltrates failed to occur. Local administration of hydrocortisone also prevented influx of PMN's in the Arthus reaction, in spite of the fact that immune reactants were found fixed in the vascular walls. Systemic treatment of guinea pigs with DNP did not diminish the intensity of the Arthus reactions.

Phagocytosis of zymosan particles by rabbit PMN's was inhibited by hydrocortisone, methyl prednisolone, and chloroquine, but not by DNP or endotoxin. The concentrations of drugs inhibitory in phagocytosis were substantially higher than those required for inhibition of chemotaxis in vitro.

These findings suggest that hydrocortisone and chloroquine inhibit the inflammatory process by preventing the response of leukocytes to chemotactic stimuli.
STUDIES ON THE EFFECT OF EXPERIMENTAL NONKETOTIC DIABETES MELLITUS ON ANTIBACTERIAL DEFENSE
Authors: Drachman Robert H. , Root Richard K. , Wood W. Barry
Published: June 2004

Chronically diabetic nonketotic rats were shown to be more susceptible to experimental Type 25 pneumococcal pneumonia than nondiabetic rats. The cumulative mortality in the diabetic group was significantly higher at infecting doses of 103, 104, 105, and 106 organisms, and the LD50 was less than one twentieth of that for the nondiabetic group. More than ten times as many viable pneumococci were found in the pneumonic lesions of the diabetic animals at 24 and 36 hr as were present in the lesions of the nondiabetic controls, and serial histologic studies revealed that phagocytosis was strikingly depressed in the alveolar exudates of the diabetic animals. The diabetic state was also found to cause a similar depression of in vivo phagocytosis in preformed peritoneal exudates.

The results of in vitro experiments indicated that the principal defect in the diabetic animals resided in their serum rather than in their polymorphonuclear leukocytes. The depressive factor in the serum was identified as the abnormally high concentration of glucose. Since equivalent molar concentrations of unmetabolized sugars added to normal serum caused a similar depression of phagocytosis, it was tentatively concluded that the action of the glucose on the leukocytes was primarily osmotic. The sensitivity of the granulocytes to the glucose effect, however, depended upon the conditions of the phagocytic test. Only when the pneumococci were encapsulated and the leukocytes derived from inflammatory exudates were crowded together, as in vivo, was the depressive action of the glucose clearly demonstrable.
PRODUCTION OF BACTERIOCINES BY GROUP A STREPTOCOCCI WITH SPECIAL REFERENCE TO THE NEPHRITOGENIC TYPES
Authors: Kuttner Ann G.
Published: June 2004

Colicinelike substances, bacteriocines, are produced by many strains of Group A and non-Group A streptococci. Bacteriocines were detected by their inhibitory action on the growth of 2 Group A strains which served as indicators.

Streptococcal bacteriocines were demonstrable on agar plates only if the bacteriocine-producing strain and the indicator lawn were alive and actively growing. The inhibitory substances diffused slowly into the agar during the course of growth. Bacteriocines were not replicated in the zones of inhibition in which the microorganisms of the indicator strains were killed. Attempts by various methods to separate bacteriocines from living bacteria were unsuccessful.

In contrast to the many strains which produced bacteriocines, only a few strains of Group A streptococci were suitable to serve as indicators for bacteriocine production. Strains of Group A streptococci of the nephritogenic types 12, 4, and 49 produced bacteriocines most consistently. Strains of other types, isolated from patients with acute rheumatic fever or from children with uncomplicated streptococcal pharyngitis, produced bacteriocines infrequently. Among non-Group A streptococci bacteriocine-positive and bacteriocine-negative strains occurred in approximately equal numbers.

It was shown by Wilson and by Bernheimer that the majority of the strains of the nephritogenic types were leukotoxic and produced DPNase. Bacteriocine production is another common characteristic property of these special types.
ENHANCEMENT OF ANTIBODY SYNTHESIS BY 6-MERCAPTOPURINE
Authors: Chanmougan Devendrathan , Schwartz Robert S.
Published: June 2004

The administration of 6-MP to rabbits led to either suppression or enhancement of antibody production, depending on when the drug was given in relation to the antigenic challenge. Maximum enhancement of antibody synthesis was found when a small dose of BGG was administered 5 days after the last dose of a 1 wk course of 6-MP. There were no indications that the macrophage system or immunological memory was affected in animals with augmented antibody synthesis. It was proposed that enhancement of antibody production by 6-MP was due to nucleic acids released from cells killed or injured by the drug. It was suggested that lymphocytes incorporating these nucleic acids were transformed into specialized cells capable of direct and immediate stimulation by antigen and lacking immunological memory (hemocytoblasts). A relatively small dose of antigen was apparently capable of stimulating all the hemocytoblasts representing a given clone) with the result that large amounts of antibody rapidly appeared in the serum.
QUANTITATIVE STUDIES OF THE IMMUNOGLOBULIN SEQUENCE IN THE RESPONSE OF THE RABBIT TO A SOMATIC ANTIGEN
Authors: Altemeier W. A. , Robbins J. B. , Smith R. T.
Published: June 2004

Employing a sensitive and immunoglobulin-specific assay method based upon antiglobulin augmentation, quantitative and qualitative aspects of the primary and secondary response of the rabbit to Salmonella typhimurium O antigens have been evaluated. These studies examine the validity of the method of assay for detecting and measuring γG- and γM-antibodies produced in response to whole organisms or its lipopolysaccharide.

The results show that during the primary response γG-antibodies, not detectable by usual techniques, are produced in a pattern similar to that reported in animals stimulated by other classes of antigens. Moreover, the γG response following reinjection is characteristic of a secondary-type response. In contrast, γM-antibody levels after both primary and secondary stimulation rose equally to levels between 1 and 4 mg/ml. Despite increased sensitivity of detection and quantitative estimates of the actual molar concentration of each immunoglobulin, the minimal interval between γM and γG appearance in serum was not less than 1.5 days. The variable degree of augmentation of agglutination by antiglobulin reagent found during the immune response severely limits the quantitative usefulness of the methods developed. However, the data suggest that qualitative changes in anti-O antibodies interpretable as changes in avidity occur regularly during the immune response.
THE INTERACTION OF MYCOPLASMAS WITH MAMMALIAN CELLS
Authors: Zucker-Franklin Dorothea , Davidson Morton , Thomas Lewis
Published: June 2004

The ultrastructure of three mycoplasma species, Mycoplasma pneumoniae, Mycoplasma gallisepticum, and Mycoplasma neurolyticum, has been studied in isolated form as well as in HeLa cell cultures and following incubation with human peripheral blood leukocytes. During log growth phase, the organisms could be distinguished from each other on the basis of their fine structure. In mammalian cell cultures, PPLO's appeared to proliferate on the plasma membranes which had markedly increased their surface area by means of long cytoplasmic processes which extended toward and surrounded them. Some of the microorganisms affected in this way may well have lain, not in vacuoles, but at the bottom of crypts.

It is suggested that the cytopathogenic effect exerted by PPLO's on some tissue cultures may be attributable to membrane damage. Mycoplasmas adhered to leukocyte plasma membranes in a similar manner. They were avidly phagocytosed by neutrophils and eosinophils with accompanying degranulation of the white cells. It is thus likely that the local inflammatory reaction induced by PPLO's does not differ in essence from that caused by bacteria.
THE INTERACTION OF MYCOPLASMAS WITH MAMMALIAN CELLS
Authors: Zucker-Franklin Dorothea , Davidson Morton , Thomas Lewis
Published: June 2004

The incubation of mycoplasmas with human peripheral blood buffy coats resulted in the uptake of these microorganisms by more than 50% of the mononuclear cells. Mycoplasmas adhered to the plasma membranes of all leukocytes, most of which developed long cytoplasmic processes not seen in the controls. In human and rat thoracic duct lymph, about 6% of the cells ingested the microorganisms. T2 phage and thorotrast were taken up by a similar percentage of lymphocytes. On morphological grounds, the cells which were able to take up PPLO's or particles could not be distinguished from the cells which were incapable of this function. Following phagocytosis, neither the cell nor the microorganism showed any morphological alterations over a 3 hr period of observation. The demonstration that a small percentage of "lymphocytes" are able to phagocytose may have pathological and immunological implications.
THE ACUTE INFLAMMATORY REACTION IN THE RABBIT EAR CHAMBER WITH PARTICULAR REFERENCE TO THE PHENOMENON OF LEUKOCYTIC MIGRATION
Authors: Cliff W. J.
Published: June 2004

Responses to injections of various materials into rabbit ear chambers were studied by in vivo microscopy. The acute inflammatory responses provoked by injections of antibody-antigen complexes were both quantitatively and qualitatively different from the responses obtained after injections of either homologous sera or the antigens alone. The sticking of leukocytes to endothelium during these responses occurred only in the venules draining the injection sites and was frequently present only on the sides of the venules towards the injection sites. An explanation of this finding was proposed in terms of absorption by the minute vessels related to the injection sites of postulated mediator(s) with specific activity on venular endothelium.

Analysis of the rates and direction of movement of leukocytes during the reactions produced by the antibody-antigen complexes was performed with the aid of time-lapse cinemicroscopy. The leukocytes that were sticking to the venular endothelium frequently exhibited amoeboid locomotion within the vessels. Twice as many of these cells moved against the direction of blood flow as with it. This finding was discussed and an explanation proposed.

A method for detecting a drift in the overall population of emigrated leukocytes within the inflamed tissue was described and revealed that four times as many amoeboid cells moved away from the injection sites as towards them. This result was discussed in the light of the in vitro chemotactic properties of antibody-antigen complexes demonstrated for rabbit leukocytes. An alternative explanation was proposed in terms of variation in the population density of these cells and their random movements and collisions.

The rates of amoeboid movement of leukocytes during the acute inflammatory reactions produced by antibody-antigen complexes were similar to the rates found during turpentine inflammation and were compared to other published values.
AN IMMUNOLOGICAL RELATIONSHIP BETWEEN THE GROUP A STREPTOCOCCUS AND MAMMALIAN MUSCLE
Authors: Zabriskie John B. , Freimer Earl H.
Published: June 2004

By means of the immunofluorescent staining technique, antisera to a wide variety of serological types of Group A and A variant streptococci were found to contain an antibody which reacted with mammalian striated muscle, both skeletal and cardiac, as well as with smooth muscle in the endocardium and in the media of arterioles. Similar heart-reactive antibodies were not present in antisera to most other groups of hemolytic streptococci and to other Gram-positive cocci. Chemical and serological studies clearly pointed to the cell (protoplast) membrane of the Group A streptococcus as the locus of the antigenic determinant of this heart-reactive antibody. In addition, preliminary studies suggested that the reaction between this streptococcal antibody and cardiac tissue represented an immunological relationship between the sarcolemma, the membrane of a mammalian muscle cell and the cell membrane of a bacterium, the hemolytic streptococcus.