bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON STRUCTURAL UNITS OF THE γ-GLOBULINS
Authors: Edelman G. M. , Poulik M. D.
Published: June 2004

When human and rabbit 7S γ-globulins were reduced in strong urea solutions by a number of procedures, their molecular weights fell to approximately ⅓ of the original values. Partial separation of the reduction products was achieved using chromatography and starch gel electrophoresis in urea solutions. One of the components of reduced human 7S γ-globulin was isolated by chromatography, identified by starch gel electrophoresis, and subjected to amino acid analyses. The amino acid composition of this component differed from that of the starting material and also from that of the remaining components.

A reduced pathological macroglobulin dissociated to components with an average molecular weight of 41,000. Several reduced human myeloma proteins, when subjected to starch gel electrophoresis, yielded individual patterns that nevertheless had features in common with those of reduced normal γ-globulins. Reduction of normal and abnormal γ-globulins was accompanied by the appearance of titratable sulfhydryl groups. Chemical treatments other than reduction were used to determine the type of bond holding the subunits together. It was tentatively concluded that they were linked by disulfide bonds. An hypothesis is presented to relate the structural features of the various γ-globulins in terms of the multiplicity of polypeptide chains in these molecules.
ANTIBODY FORMATION
Authors: Uhr Jonathan W. , Baumann Joyce B.
Published: June 2004

The suppression of antibody formation by passively administered antibody is influenced by the dose and nature of the antigen, type of immunization procedure, ratio of antibody to antigen, species origin and characteristics of the antiserum used, as well as the species selected for immunization. In guinea pigs, diphtheria antitoxin formation can be effectively suppressed by an intravenous injection of excess homologous or heterologous antitoxin as long as 5 days after toxoid immunization and after delayed-type hypersensitivity to toxoid has developed. Following the period of antibody suppression which lasts 2 to 7 weeks, serum antibody can usually be demonstrated. It is proposed that this delayed immunization results from dissociation of antigen, since diphtheritic paralysis and death can be produced in guinea pigs and rabbits by the intravenous injection of toxin-antitoxin precipitates formed in antitoxin excess. This syndrome is prevented by injection of excess horse antitoxin 1 hour after injection of the toxin-antitoxin complexes.
ANTIBODY FORMATION
Authors: Uhr Jonathan W. , Baumann Joyce B.
Published: June 2004

Diphtheria toxoid-antitoxin precipitates formed in antitoxin excess can prepare guinea pigs, rats, and rabbits for a secondary type of antitoxin response. Priming may occur without the development of detectable serum antibody. In rats, toxoid-antitoxin precipitates are more efficient than "free" toxoid in priming, whereas in guinea pigs, the magnitude of the anamnestic response varies with the precipitate employed. The possibility that priming is due to "free" antigen released from the specific precipitate rather than the precipitate itself is discussed. The anamnestic antitoxin response can be inhibited by passive antitoxin, but less efficiently than primary antitoxin formation. Partial suppression of the secondary antitoxin response was accomplished by injection of excess horse antitoxin as long as 4 days after reimmunization with toxoid. The importance of these findings for the understanding of passive-active immunization in the human is discussed.
THE ANALYSIS OF STREPTOCOCCAL INFECTIONS
Authors: Halbert Seymour P. , Keatinge Suzanne L.
Published: June 2004

It has been found by immunoelectrophoresis, that Group A streptococci release at least 20 distinct extracellular antigens in human tissues, as judged by naturally occurring antibodies present in normal pooled human gamma globulin.

Several of these precipitin arcs have been identified with streptococcal antigens previously purified by electrophoresis and chromatography.

Human gamma globulin, as well as several rheumatic fever sera, were shown to be remarkably potent in antistreptococcal antibodies, when compared to four horse antibody concentrates obtained by hyperimmunization with several streptococcal filtrates.

A Group C streptococcal culture concentrate revealed 8 or 9 antigens for which corresponding antibodies were present in human gamma globulin.
EFFECTS OF CHRONIC EXCESS SALT FEEDING
Authors: Dahl Lewis K. , Heine Martha
Published: June 2004

Female rats were fed diets containing either excess sea salt or excess sodium chloride for periods up to 14 months. The hypertension produced by sea salt was more pronounced than that caused by sodium chloride alone, although the average amount of sodium chloride contained in the sea salt feeding was slightly less. The ions involved in this incremental effect of sea salt were not identified.
OBSERVATIONS ON THE PRODUCTION OF PYROGENIC SUBSTANCES BY RABBIT AND HUMAN LEUCOCYTES
Authors: Fessler J. H. , Cooper K. E. , Cranston W. I. , Vollum R. L.
Published: June 2004

1. The mechanism of release of a pyrogen from leucocytes has been studied in cells obtained from sterile rabbit peritoneal exudates and from rabbit blood. Attempts were made to induce human leucocytes—from blood—to release a pyrogen.

2. Rabbit leucocytes, kept below 4°C., were not pyrogenic and did not release any pyrogen when disintegrated. Incubating such cells, in various media, at 37°C. led to the formation of a pyrogen which was heat-labile. The maximum yield was attained after 1½ hours' incubation.

3. The formation of rabbit leucocytic pyrogen was prevented by freezing and thawing the leucocytes, by heating them to 56°C. for half an hour before incubation, and by ageing them in the cold.

4. Nitrofurazone (5-nitro-2-furaldehyde semicarbazone) prevents the formation of leucocytic pyrogen when given by mouth to the cell-donor animals, or when added to leucocytes in intro.

5. Leucocytes from rabbit blood formed leucocytic pyrogen, on incubation in saline, and this formation was also inhibited by nitrofurazone.

6. No leucocytic pyrogen was released from human leucocytes subjected to mechanical, osmotic, or thermal damage, and it was not formed when the cells were incubated in saline.

7. The source of rabbit leucocytic pyrogen, the action of nitrofurazone on leucocytes, and the supposed role of leucocytic pyrogen in fever are discussed.
MORPHOLOGIC ALTERATIONS PRODUCED BY COPPER IN NEURAL TISSUES WITH CONSIDERATION OF THE ROLE OF THE METAL IN THE PATHOGENESIS OF WILSON'S DISEASE
Authors: Vogel F. Stephen , Evans John W.
Published: June 2004

The injection into the cerebrospinal fluid of cats of 52 to 208 gamma of copper in the form of an albumin complex or as cupric sulfate, was followed by small elevations in the content of metal in the neural tissues, but regularly and promptly produced persistent quadriplegia and conspicuous histologic changes. Smaller amounts of copper caused less, or no, neurologic manifestations or histologic alterations. The earliest lesions were essentially unaccompanied by inflammation and were initially characterized by hydropic swelling of the myelin sheaths. They progressed rapidly to focal necrosis of all parenchymal components with marked degeneration of myelin and axis cylinders in the peripheral margins of the spinal cord, brain stem, mid-brain, and cerebrum. These histologic changes did not occur in neural tissues incubated in vitro in solutions of the copper-albumin complex. They did not appear in animals injected intraventricularly with ferric sulfate or saccharated iron. Considered together, the findings make it clear that copper in concentrations comparable to those present in the neural tissues of patients with Wilson's disease has the property of profoundly altering neural function and causing conspicuous morphologic alterations.
STUDIES ON THE CHEMICAL STRUCTURE OF THE STREPTOCOCCAL CELL WALL
Authors: Krause Richard M. , McCarty Maclyn
Published: June 2004

Lysis of trypsinized Group A streptococcal cell walls with phage-associated lysin releases into solution dialyzable and non-dialyzable mucopeptide fractions composed of N-acetylglucosamine, N-acetylmuramic acid and alanine, glutamic acid, lysine, and glycine in addition to the characteristic group-specific carbohydrate. The latter substance contains appreciable amounts of N-acetylmuramic acid and the amino acids as well as N-acetylglucosamine and rhamnose.

Hot formamide extraction of the cell walls results in a soluble fraction of group-specific carbohydrate and an insoluble residue. The Group A carbohydrate in this instance is composed of rhamnose and N-acetylglucosamine. The composition of the insoluble residue is similar to that of the mucopeptide fractions released from the cell wall by phage-associated lysin. This residue was shown by electron microscopy to be composed of discrete discs which appear similar in structure to the intact cell wall.

The specific carbohydrate obtained by hot formamide extraction of Group A-variant cell walls was composed almost exclusively of rhamnose. The residue fraction was similar to that of Group A.

The residue of cell walls extracted with hot formamide is extensively solubilized not only by phage-associated lysin and S. albus enzyme, but also by lysozyme, which has no measurable effect on the intact streptococcal cell wall.
ANAPHYLAXIS IN CHOPPED GUINEA PIG LUNG
Authors: Austen K. F. , Brocklehurst W. E.
Published: June 2004

The anaphylactic release of histamine from perfused, chopped guinea pig lung is very sensitive to changes in the NaCl concentration of the containing medium, and it is ionic strength rather than particle concentration which is critical. Consequently, in studies with inhibitors care must be taken to avoid inadvertently increasing ionic strength and thereby misinterpreting the cause of the inhibition.

Since immune hemolysis exhibits a similar sensitivity to changes in the NaCl concentration of the suspending medium, salicylaldoxime and phlorizin, which prevent the participation of the third component of complement in immune hemolysis, were investigated for their effect on the anaphylactic reaction. Salicylaldoxime is a potent inhibitor of in vitro anaphylaxis in guinea pig lung, but phlorizin is only a weak inhibitor.

Potassium cyanide, 1 mM, inhibits the anaphylactic release of histamine most effectively if the duration of contact between the tissue and the cyanide prior to antigen addition is minimal; preincubation of the tissue with cyanide prior to antigen addition results in progressive diminution of inhibition even when there is only minimal loss of cyanide from the containing medium.

The anaphylactic release of histamine from perfused whole lungs or suspensions of blood-free chopped lung is not prevented by the cytochrome oxidase inhibitor, carbon monoxide. In addition, 2-heptyl 4 hydroxyquinoline N oxide and malonic acid, which inhibit aerobic metabolism at different sites, do not prevent the reaction. These studies and those with cyanide indicate that the anaphylactic release of histamine in guinea pig lung is not dependent on cytochrome-mediated aerobic metabolism.
FACTORS AFFECTING THE ADHESIVENESS OF HUMAN LEUCOCYTES AND PLATELETS IN VITRO
Authors: Garvin James E.
Published: June 2004

Some factors affecting the retention of human polymorphonuclear neutrophils (PMN), lymphocytes, and platelets on a siliconized glass bead column were explored.

PMN were more effectively retained when the flow rates were slow and the columns long. They were found largely on the upper portions of the columns except with rapid flow rates when they spread down the columns. PMN retention on the columns was greatest in the range 30°–43°C. Both magnesium and calcium ions were required for full adhesiveness; calcium ions alone were unable to restore adhesiveness to PMN from blood which had been treated with a chelating resin to remove divalent cations. The adhesiveness of the PMN was independent of cyanide and dinitrophenol, but was almost completely eliminated by iodoacetamide. Under all the conditions mentioned above in which adhesiveness was lost there was a concurrent loss of the usual ability of the PMN to migrate, but at least in the presence of EDTA, a capacity to change shape by pseudopod formation remained.

Lymphocytes were retained on the columns to a much lesser extent than the PMN under all conditions and, within limits, this retention was not related to either flow rate or column length. Maximum lymphocyte retention occurred in the range 30°–43°C. No dependence of lymphocyte adhesiveness was shown for divalent cations, cyanide, dinitrophenol, or iodoacetamide, but such dependence is not excluded by the data obtained.

Platelets were largely retained by the glass bead columns under most conditions and this was unrelated to temperature in the range 0°–50°C. Their adhesiveness was found to require either magnesium or calcium ions and to be blocked by iodoacetamide.
THE EFFECT OF AMINOMETHYLPTEROYLGLUTAMIC ACID ON THE DEVELOPMENT OF SKIN HYPERSENSITIVITY AND ON ANTIBODY FORMATION IN GUINEA PIGS
Authors: Friedman Robert M. , Buckler Charles E. , Baron Samuel
Published: June 2004

1. In guinea pigs, aminomethylpteroylglutamic acid (methotrexate) is capable of blocking the development of delayed skin hypersensitivity, the primary antibody response, and the specific febrile response to ovalbumin and diphtheria toxoid. The primary antibody response is more easily inhibited than is the development of delayed skin hypersensitivity.

2. The effect of methotrexate on immunologic responses depended upon the dose of methotrexate employed and the strength of the antigenic stimulus.
THE SPECIFICITY OF ALLERGIC REACTIONS
Authors: Salvin S. B. , Smith R. F.
Published: June 2004

Intradermal injection of a simple hapten (e.g., 1-fluoro-2,4-dinitrobenzene) in water-in-oil emulsion results in contact hypersensitivity to surface application of the homologous hapten and, after appearance of circulating antibody, in Arthus type hypersensitivity to a conjugate of homologous hapten with guinea pig serum. Intradermal administration of this conjugate induces delayed and subsequently Arthus hypersensitivity to the conjugate, but no evidence of a contact reaction to the hapten alone. When a conjugate of hapten plus solubilized guinea pig skin is used as the sensitizing antigen, both contact hypersensitivity to the hapten and delayed and/or Arthus reactions to the conjugate develop. These observations are consistent with the hypothesis that the specificity of contact sensitivity is directed toward some particular protein of the skin which has been modified by combination with hapten.
PATHOGENESIS OF EXPERIMENTAL SHOCK
Authors: Nagler Arnold L. , Zweifach Benjamin W.
Published: June 2004

A series of biological test reactions was used in order to establish the presence of bacterial endotoxins in the blood of rabbits during the progression of hemorrhagic shock.

1. When the shocked animal was used as the test object, it was not possible to induce either the generalized Shwartzman reaction or the dermal Shwartzman phenomenon with exogenous endotoxin (S. enteritidis or E. coli) as one of the two provocative factors.

2. Epinephrine instilled into the skin of rabbits either before, during, or after an episode of hemorrhagic shock did not result in the hemorrhagic skin reaction which occurs in the presence of as little as 1 µg of endotoxin intravenously.

3. Passive transfer from a donor in the irreversible phase of shock of 20 to 25 ml of blood into a primed recipient (B.P. at 40 mm Hg for 1 hour) was uniformly lethal.

4. Similar amounts of blood from such shocked donor failed upon intravenous injection to elicit a protective hemorrhagic reaction in skin sites which were infiltrated with 100 µg of epinephrine. In the same animals 1 µg of endotoxin added to the blood samples caused a positive dermal response.

5. Blood was taken from rabbits which had been pretreated with S. enteritidis endotoxin and then subjected to hemorrhagic shock (35 mm Hg for 2 hours). Such samples upon passive transfer produced positive skin reactions in epinephrine sites but were not lethal to the primed test recipient used in these studies.

It is concluded that the contribution of bacterial endotoxemia to the genesis of hemorrhagic shock remains to be determined.
PATHOGENESIS OF EXPERIMENTAL SHOCK
Authors: Janoff Aaron , Nagler Arnold L. , Baez Silvio , Zweifach Benjamin W.
Published: June 2004

Donor rabbits were subjected to shock by occlusion of the superior mesenteric artery (SMAO shock). Portal blood was collected from these animals at certain intervals after release of the arterial ligature. Infusion of this blood into sub-lethally hemorrhaged rabbits caused the death of half of the tested animals; a mortality incidence which closely matched the per cent mortality in rabbits shocked by SMA occlusion alone. Blood from sham-operated donor animals did not prove lethal when infused into hemorrhage-prepared rabbits.

Infusion of SMAO shock plasma did not result in the death of recipient animals, even though the whole blood source of the plasma had proven to be lethal upon infusion into hemorrhage-prepared rabbits. Moreover, following pretreatment of donor animals with a non-absorbable antibiotic per os, the number of actively reproducing bacteria in the intestinal fluids was reduced to less than 0.1 per cent of normal; nevertheless, the incidence of passive transfer of lethality from shocked donors receiving this pretreatment was not consistently reduced. Furthermore, when SMAO shock portal blood was tested for the presence of bacterial endotoxin by the sensitive dermal epinephrine reaction, although some blood samples demonstrated lesion-provoking activity, there was no correlation between this activity and the lethal properties of the blood samples.

In seeking an explanation for the production of dermal epinephrine lesions by non-lethal shock blood, a positive correlation was demonstrated between the lesion-provoking activity of portal blood and the serotonin content of intestinal tissues of rabbits shocked by SMA ligation. In addition, small amounts of serotonin were shown to be capable of provoking dermal epinephrine reactions in rabbits, under the same conditions used to test the lesion-provoking activity of portal blood.

It was therefore concluded that: (a) a toxic factor(s) is present in the portal blood of SMAO-shocked rabbits; (b) that this factor(s) is not likely to be a bacterial endotoxin; and (c) that the occasional provocation of a dermal epinephrine reaction by portal blood from SMAO-shocked rabbits, a property heretofore exclusively attributed to the presence of endotoxin in shock blood, can be entirely explained on the basis of elevated levels of serotonin in this blood.
A COMPARISON OF THE PEPTIDES RELEASED FROM RELATED RABBIT ANTIBODIES BY ENZYMATIC HYDROLYSIS
Authors: Gitlin David , Merler Ezio
Published: June 2004

Rabbit antibodies against pneumococcus capsular polysaccharides of Types II, III, VI, VII, and XII were isolated from type-specific antisera by precipitation with homologous antigen and hydrolyzed with either subtilisin, chymotrypsin or trypsin. Purified antibodies were also hydrolyzed with papain; the two polypeptides with active antibody sites and the crystallizable polypeptide were separated, studied in the ultracentrifuge and hydrolyzed with either subtilisin or chymotrypsin. The resulting peptides were separated on filter paper by electrophoresis and chromatography.

1. The two polypeptides with antigen-combining activity, fractions I and II, each constituted about 25 per cent of the original antibody molecule; the crystallizable polypeptide did not combine with antigen, fraction III, and represented about 35 per cent of the original antibody molecule. About 10 to 15 per cent of the original antibody molecule was hydrolyzed by papain into about 35 peptides.

2. The peptide patterns obtained for hydrolyzates of fraction I were almost identical with those obtained for fraction II obtained from the same antibody and were quite different for those obtained for fraction III.

3. Many of the peptide spots in the patterns obtained with whole antibody hydrolysates contained at least two peptides derived from different parts of the antibody molecule.

4. Differences were observed in the peptide patterns for different antibodies that suggested the existence of differences in both primary and tertiary structures among these antibodies.
TRITON HYPERLIPEMIA IN DOGS
Authors: Scanu Angelo , Oriente Pasquale , Szajewski Janusz M. , McCormack Lawrence J. , Page Irvine H.
Published: June 2004

Fourteen dogs, fed a regular diet and given 250 mg/kg of triton (a non-ionic surface-active agent) intravenously every 4th day, exhibited a progressively severe hyperlipemia. Serum triglycerides were the first to increase. Cholesterol, mostly in the free form, and phospholipids showed elevation only at a later stage and increased at almost identical rates. The plasma-free fatty acid concentration was from 2 to 3 times above normal.

With establishment of sustained hyperlipemia, there was reduction, followed by total disappearance, of the high density D 1.063 to 1.21 lipoprotein. Most of the cholesterol and phospholipids (70 to 75 per cent of the total) were found in the D 1.006 to 1.063 lipoprotein class, the remainder in the D < 1.006 class. Triglycerides were almost evenly distributed between these two classes. The concentration of the serum lipoprotein proteins was within normal limits.

All of the animals died within from 4 to 5 months after receiving the first injection of triton. Autopsy findings consistently showed: (a) numerous lipidladen macrophages in the liver, spleen, and lymph nodes; (b) significant depletion of all fat stores; (c) presence of lipids, either free or engulfed in macrophages (foam cells), in the subintima of the coronary arteries, aorta, and pulmonary arteries, indicating an early stage of atherosclerosis.

Concurrent daily administration of heparin (5 mg per kilogram of body weight) did not substantially change the course of the disease.

Withdrawal of triton from animals that had been receiving the detergent for from 3 to 4 months, elicited a slow return to normal of the lipid pattern. In two dogs killed when normolipemia was reestablished, all tissues were normal with the minor exception of a few hepatic macrophages still laden with sudanophilic material.

It is postulated that the primary action of the injected triton was on the lipid moieties of plasma lipoproteins with formation of complexes, which, as foreign bodies, were preferentially taken up by the cells of the reticuloendothelial system. Depletion of fat stores was probably secondary to increased lipid mobilization, as an attempt by these tissues to supply energy to the parenchymal cells unable to utilize triton-bound lipids.
STRUCTURAL REQUIREMENTS FOR LATHYROGENIC AGENTS
Authors: Levene C. I.
Published: June 2004

Using the chick embryo assay system, a series of organic compounds was tested for lathyrogenic activity; lathyrogenic compounds were shown to fall into 4 groups—nitriles, ureides, and 2 new groups—hydrazides and hydrazines, forming a spectrum of diminishing potency in their ability to produce solubility of collagen and skeletal deformities.

Pyridoxal was seen to reverse to a great degree the effects on collagen solubility and skeletal deformity produced by the ureides and hydrazides, though not by the nitriles; its effect was considered to be due to the formation of a Schiff's complex between the aldehyde and the terminal amine of the lathyrogen. Evidence is presented to show that lathyrogens do not act as inhibitors of monoamine oxidases or as chelate-forming agents, nor, in the case of isoniazid, as an anti-nicotinamide agent.
STUDIES ON INFECTION AND IMMUNITY IN EXPERIMENTAL TYPHOID FEVER
Authors: Gaines Sidney , Landy Maurice , Edsall Geoffrey , Mandel Adrian D. , Trapani R.-J. , Benenson A. S.
Published: June 2004

A study was made of the efficacy of various antityphoid immunizing agents in immunizing chimpanzees against typhoid fever produced by feeding viable S. typhosa.

It was found that both acetone-killed and heat-killed, phenol-preserved typhoid vaccines were effective in protecting against infection induced with either homologous or heterologous strains of typhoid bacilli.

Purified O antigen induced no discernible protection, but some immunity was afforded by the administration of purified Vi antigen.
IMMUNOCHEMICAL STUDIES OF TWENTY MOUSE MYELOMA PROTEINS: EVIDENCE FOR TWO GROUPS OF PROTEINS SIMILAR TO GAMMA AND BETA-2A GLOBULINS IN MAN
Authors: Fahey John L.
Published: June 2004

The serum myeloma proteins associated with 20 mouse plasma cell tumors in C3H or BALB/c mice that had proved transplantable were characterized by electrophoretic and immunochemical techniques. Although the myeloma proteins ranged in electrophoretic mobility from gamma to alpha globulins, they could be divided into two groups, the gamma type and the beta type myeloma globulins, on the basis of characteristic immunochemical properties. Gamma type myeloma proteins (5563, MPC-11) showed a close immunochemical relationship to normal mouse gamma globulins.

Eighteen beta type mouse myeloma proteins migrated as beta or alpha globulins on zone electrophoresis. These proteins shared common antigenic features which permitted their recognition, separate from gamma myeloma proteins. The beta type myeloma proteins were shown to be related to a beta globulin component present in normal serum. Strain differences were observed for the normal beta globulin component believed to be formed in plasma cells.

The proteins formed in mouse plasma cells were found to be antigenically complex. Shared antigenic determinants as well as distinctive antigenic determinants were detected when representative myeloma proteins were purified and compared by the Ouchterlony double diffusion technique.

The myeloma proteins associated with each of the transplantable plasma cell tumors in mice are regarded as distinctive and characteristic products of plasma cell metabolism. The variety of myeloma globulins was similar for plasma cell tumors arising in C3H as well as in BALB/c mice, indicating that differences in mouse strains would not account for the differences among the myeloma globulins. These differences, however, may be due to differences among the normal plasma cells from which the malignant cells are derived. If this is so, the variety of myeloma globulins reflect the variety of plasma cells present normally.
PHYSICOCHEMICAL CHARACTERIZATION OF MOUSE MYELOMA PROTEINS: DEMONSTRATION OF HETEROGENEITY FOR EACH MYELOMA GLOBULIN
Authors: Fahey John L.
Published: June 2004

Physicochemical characterization of mouse myeloma proteins revealed the individuality of each myeloma protein. When the myeloma proteins are considered collectively a wide range of individual properties were represented, including electrophoretic mobilities varying from the gamma to alpha region, hexose contents from 1 to 4 per cent, and ultracentrifugal components from 6.5 to 13 S. The 20 myeloma proteins could be divided into groups, the gamma type and the beta type myeloma globulins, on the basis of physicochemical, as well as immunoelectrophoretic, studies. Two gamma type myeloma proteins (5563, MPC-11) resembled normal gamma globulins, sedimenting as a single 6.5 S peak in the ultracentrifuge, and having a relatively low hexose content (1 per cent).

Eighteen beta type mouse myeloma proteins differed from gamma myeloma proteins and, typically, were found on ultracentrifugal analysis to have multiple components with sedimentation coefficients of 6.5, 9, 11, and 13 S, having a higher hexose content (2 to 4 per cent) as well as distinctive chromatographic and starch gel electrophoretic properties.

All of the mouse myeloma proteins were heterogeneous and heterogeneity of two types was observed. Polymer formation was responsible for the 9, 11, and/or 13 S components seen on ultracentrifugation of the beta type myeloma proteins. Starch gel electrophoresis revealed this type of heterogeneity as relatively widely separated myeloma protein components, presumably owing to the retardation effect of starch gel on the electrophoretic migration of the larger polymers. Starch gel electrophoresis revealed a different type of heterogeneity for the two gamma type myeloma proteins, each of these being shown to contain 5 or more components differing only in electrophoretic properties.

The physicochemical characteristics of the γ-type and ß-type myeloma proteins in the mouse indicated the close similarity of these proteins to the γ- and ß-2A-myeloma proteins in man.
DEMONSTRATION OF MOUSE ISOANTIGENS AT THE CELLULAR LEVEL BY THE FLUORESCENT ANTIBODY TECHNIQUE
Authors: Möller Göran
Published: June 2004

The fluorescent antibody technique has been applied for the demonstration of mouse isoantigens at the cellular level. Specific reactions were obtained by the indirect or "sandwich" technique with a variety of living normal and neoplastic cells. Isoantigens of the H-2 system and of other systems could be demonstrated as well and appeared to be localized at the cell membrane. As far as the H-2 system was concerned, the membrane localization could be confirmed on histological sections.

Different types of non-specific staining reactions have been identified and described. Pinocytosis and cell injury led to such reactions that were morphologically distinguishable from the specific "ring" reaction and as far as pinocytosis is concerned, could be easily avoided by reducing the incubation time. In addition, a non-specific staining reaction morphologically indistinguishable from the specific "ring" reaction could be seen in a small proportion of bone marrow and lymph node cells but in no other cell type studied. The possible nature of this reaction is discussed.
SITES OF FORMATION OF IMMUNE GLOBULINS AND OF A COMPONENT OF C'3
Authors: Hochwald G. M. , Thorbecke G. J. , Asofsky R.
Published: June 2004

The development of a new method for the determination of the sites of serum protein formation has been described. The method involves the incorporation of C14-labeled amino acids by tissues cultured in vitro, and subsequent autoradiography of immunoelectrophoretic patterns prepared from a mixture of culture fluids and carrier serum with an antiserum against the carrier serum.

This technique has been used to demonstrate formation of γ-globulin, of ß2-macroglobulin, and of a component of C'3 by mouse spleen tissue, and of various other serum proteins by liver tissue. The specificity and sensitivity of this method have been discussed, and some of its advantages and pitfalls were mentioned.

In addition, a rabbit antimouse serum was prepared, and the immunoelectrophoretic patterns obtained with mouse serum were compared with those described in the literature.
SITES OF FORMATION OF IMMUNE GLOBULINS AND OF A COMPONENT OF C'3
Authors: Asofsky R. , Thorbecke G. J.
Published: June 2004

Human, and monkey tissues were cultured in the presence of labeled amino acid. The culture fluids were then examined for labeled serum proteins by means of autoradiography of immunoelectrophoretic patterns prepared from mixtures of the fluids and carrier sera. Gamma globulin, ß2A-globulin, ß2Mglobulin, and ß1C-globulin were found to be formed in human lymph node, bone marrow, and ileum. Gamma globulin, ß2M-globulin, and ß1C-globulin were found to be formed in monkey spleen, lymph node, and bone marrow. Formation of several other serum proteins was observed in the monkey liver.
A LABILE SERUM FACTOR IN EXPERIMENTAL ENDOTOXIN SHOCK: CROSS-TRANSFUSION STUDIES IN DOGS
Authors: Spink Wesley W. , Vick James
Published: June 2004

Peripheral vascular failure caused by endotoxin in the dog has an initial stage of vasoconstriction. Preliminary studies in vitro demonstrated that the constriction was due to the interaction of endotoxin with a heat-labile serum or plasma factor and platelets, resulting in the liberation of histamine. Further studies on the intact dog support and extend this concept.

A standardized dose of Escherichia coli endotoxin produced fatal shock in control adult mongrel dogs within 28 hours. The characteristic pattern of changes included progressive hypotension, oliguria and anuria, hemoconcentration, and acidosis.

Normal dogs were protected against endotoxin by transfusions of blood in which the essential serum factor was depleted in one of two ways. First, plasma separated from the blood of normal animals was heated at 56°C for 30 minutes, and the infused reconstituted whole blood protected normal dogs. Protection was not afforded by unheated reconstituted blood. Second, blood from immune dogs obtained within 24 hours after a second lethal dose of endotoxin protected recipient dogs. However, protection was not demonstrated with blood collected 72 hours after a second injection of endotoxin.

The nature of the serum factor essential for endotoxin activity is not known. It is postulated that an enzyme or enzyme system is involved, and the possible role of complement is discussed.
THE BEHAVIOR OF THREE DIFFERENT KINDS OF ANTIBODIES IN TUBERCULOSIS: ANTIPROTEIN, ANTIPOLYSACCHARIDE, AND ANTIPHOSPHATIDE
Authors: Takahashi Yoshio , Onodera Tadazumi , Yamamoto Ken-Ichi
Published: June 2004

The mode and the level of production of the three different kinds of antibodies, antipolysaccharide, antiprotein, and antiphosphatide, were found to differ considerably with the mode of infection and the virulence of tubercle bacilli. Evidence is given that production of the antipolysaccharide and antiprotein is stimulated without regard to the mode of infection and the virulence of bacilli, while the antiphosphatide is produced chiefly under conditions where in vivo bacilli might have undergone destruction. Of the three antibodies, the level of antiphosphatide was shown to reflect most faithfully the progression of experimental tuberculous infection.

The amounts of the three circulating antibodies were found to have no direct relationship to the degree of tuberculin skin hypersensitivity.
COMPLEMENT FIXATION IN DISEASED TISSUES
Authors: Burkholder Peter M.
Published: June 2004

An immunohistologic complement fixation test has been used in an effort to detect immune complexes in sections of kidney from rats injected with rabbit anti-rat kidney serum and in sections of biopsied kidneys from four humans with membranous glomerulonephritis. Sections of the rat and human kidneys were treated with fluorescein-conjugated anti-rabbit globulin or antihuman globulin respectively. Adjacent sections in each case were incubated first with fresh guinea pig serum and then in a second step were treated with fluorescein-conjugated antibodies against fixed guinea pig complement to detect sites of fixation of the complement. It was demonstrated that the sites of rabbit globulin in glomerular capillary walls of the rat kidneys and the sites of localized human globulin in thickened glomerular capillary walls and swollen glomerular endothelial cells of the human kidneys were the same sites in which guinea pig complement was fixed in vitro. It was concluded from these studies that rabbit nephrotoxic antibodies localize in rat glomeruli in complement-fixing antigen-antibody complexes. Furthermore, it was concluded that the deposits of human globulin in the glomeruli of the human kidneys behaved like antibody globulin in complement-fixing antigen-antibody complexes. The significance of demonstrating complement-fixing immune complexes in certain diseased tissues is discussed in regard to determination of the causative role of allergic reactions in disease.
BIOLOGICAL PROPERTIES OF PARENT ENDOTOXINS AND LIPOID FRACTIONS, WITH A KINETIC STUDY OF ACID-HYDROLYZED ENDOTOXIN
Authors: Haskins Willard T. , Landy Maurice , Milner Kelsey C. , Ribi Edgar
Published: June 2004

The biological potencies of a number of lipid fractions separated from endotoxins by acid hydrolysis, including the material known as lipid A, were determined in parallel with those of their parent endotoxins, employing bio-assays based on the following dose-related host responses: fever, resistance to infection, tumor damage, primary inflammation of skin, and lethality. Without exception, lipid fractions dispersed by detergents exerted less than 1 per cent of the biological activity of the potent endotoxins from which they were derived.

A study was made of the rate at which biologic activities diminished in relation to the release of bound lipid during progressive hydrolysis of Salmonella enteritidis endotoxin with dilute acid. Each of the five assays for endotoxin revealed that biological activity had been reduced to negligible proportions prior to any significant liberation from the endotoxin of water-insoluble firmly bound lipid. The major pharmacological activity of endotoxins, therefore, is acid-labile and cannot be accounted for in isolated lipids. This conclusion is also supported by the finding that lipids with activity similar to that of lipid A could be obtained by non-hydrolytic methods without diminishing the potency of the parent endotoxins.
PASSIVE TRANSFER OF TUBERCULIN SENSITIVITY BY TRITIATED THYMIDINE-LABELED LYMPHOID CELLS
Authors: Najarian John S. , Feldman Joseph D.
Published: June 2004

Passive transfer of tritiated thymidine-labeled BCG sensitized lymphoid cells into homologous guinea pigs resulted in positive tuberculin skin reactions 24 hours after testing with PPD. Labeled cells were found specifically attracted to these sites. Labeled non-sensitized lymphoid cells did not appear at PPD injection sites, nor did labeled sensitized cells accumulate in non-specific inflammatory lesions. The specifically reacting tritiated cells were small, medium, and large lymphocytes and stem or immature cells of the lymphoid series. In the homologous system employed, positive skin tests were either minimal or absent 3 days after transfusion of activated cells. The injected labeled sensitized cells were rapidly cleared from the circulating blood and lodged in the lungs, spleen, and lymph nodes. Upon application of specific antigen they reappeared at the skin test site at 6 hours and then increased in number for the next 18 hours.
THE RELEASE OF CHOLESTEROL ESTERS FROM SERUM LIPOPROTEINS BY EXTRACTS OF CERTAIN GROUP A STREPTOCOCCI
Authors: Rowen Robert
Published: June 2004

A chemical explanation has been provided for the production of opalescence in human and animal sera by extracts of certain Group A streptococci. Opalescence results from the selective liberation of specific lipids from α1-serum lipoprotein. The released lipids have been quantitatively separated through the relatively simple technique of ultracentrifugal flotation, and subsequently analyzed by chemical and chromatographic means. Esterified cholesterol constitutes by far the major low density reaction product, accounting for 85 to 90 per cent of the total lipid released. A small amount of phospholipid (apparently limited to lecithin) was the only other lipid consistently found in low density product fractions.

Comparative kinetics of opalescence development and cholesterol release under varying conditions of pH, extract concentration, and temperature reveal that the two effects do not run exactly parallel but are, nevertheless, probably closely related manifestations of a specific enzymic degradation of serum lipoprotein. It has been suggested that enzymic action may occur at a site within the lipoprotein remote from the cholesterol esters themselves. Although the over-all reaction appears to be mediated by an enzyme present in many Group A streptococci, it is uncertain whether this enzyme acts directly on lipoprotein or acts by causing the activation of a serum enzyme which in turn attacks the lipoprotein.
A STUDY IN VITRO OF COMPONENTS IN THE TRANSMISSION CYCLE OF SWINE INFLUENZA VIRUS
Authors: Peterson W. D. , Davenport Fred M. , Francis Thomas
Published: June 2004

Swine lungworm extracts and suspensions of swine lungworms contain receptor-like substances capable of adsorbing influenza virus, a result consonant with the hypothesis (5–8) that the lungworm may be involved in the swine influenza cycle. Yet no evidence for multiplication of virus or even persistence of infectious virus in lungworms at undimished titer was found. Clearly much more information is needed, and it is hoped that the present demonstration of the practicality of studying the components of the transmission cycle proposed by Shope, will provide important tools requisite for further investigation of this problem.

Studies on the role of the earthworm in the transmission of swine influenza suggest that, at best, that role would be a passive one.
MOLECULAR HETEROGENEITY OF LACTIC DEHYDROGENASE IN AVIAN MALARIA (PLASMODIUM LOPHURAE)
Authors: Sherman Irwin W.
Published: June 2004

Lactic dehydrogenase activity increased in direct proportion to the degree of parasitization in synchronous infections of duck erythrocytes. Deviations from this linearity could be accounted for on the basis of the developmental stage of the parasite. Erythrocyte-free P. lophurae showed activities which averaged 3 times that of uninfected erythrocytes, whereas infected erythrocytes had intermediate values. In addition, a patent infection was generally reflected by an increase in the lactic dehydrogenase activity in the plasma, but no direct correlation with parasitemia was established.

Molecular heterogeneity of the enzyme was determined on the basis of kinetic data and electrophoretic isolation on a starch block. The uninfected red blood cell showed a major anodal and a minor cathodal peak of lactic dehydrogenase activity, and was further characterized by a kinetic constant representing a high pH optimum with low concentrations of substrate. Isolated P. lophurae had a single, cathodal peak of activity dissimilar from that of the uninfected erythrocyte, and a kinetic constant describing a low pH optimum with a high concentration of substrate. Infected erythrocytes showed a combination of these electrophoretic entities and an intermediate range of kinetic constants.

The data indicate that the avian malaria parasite P. lophurae contains a lactic dehydrogenase qualitatively dissimilar from that of its host cell, and the increased enzymatic activity of infected erythrocytes is a result of the enzyme content of the growing parasite added to that of the red blood cell. It is suggested that the LDH of the parasite has a physiological advantage under those conditions which prevail inside the red blood cell.
ANTIBACTERIAL EFFECTS ASSOCIATED WITH CHANGES IN BACTERIAL CYTOLOGY PRODUCED BY CATIONIC POLYPEPTIDES
Authors: Spitznagel John K.
Published: June 2004

The antibacterial action of cationic polypeptides has been found to be correlated with changes which they produce in the cytochemical reactions of the bacterial cells. Bacterial cells ordinarily stain with cationic dyes at pH values above 7. Treatment with cationic polypeptides rendered them stainable with the anionic dye fast green at pH 8.1. This change occurred parallel to loss of bacterial viability.

An anionic, biological substance, mucin, was found to inhibit the usual conversion of bacterial cells from strong basophilia to strong acidophilia in the presence of cationic polypeptide. This inhibitory action was paralleled by inhibition of the toxicity of the cationic polypeptides for the bacterial cells. It was found that the basic protein, globin, which has a lesser pK than total calf thymus histone, was less toxic for E. coli and less effective in causing the bacterial cells to become stainable with the anionic dye at high pH.

Staining with fast green at pH 8.1 appeared to provide presumptive evidence of lethal interaction between certain bacterial cells and cationic polypeptides such as total histones. It is suggested that the method may prove to be useful in the detection of lethal interaction between cationic polypeptides of the host and bacteria residing in host tissues.
STUDIES ON TUBERCULIN FEVER
Authors: Moses John M. , Atkins Elisha
Published: June 2004

Certain characteristics of tolerance which develops to the pyrogenic effects of old tuberculin (OT) in BCG-vaccinated rabbits have been described.

Rabbits made tolerant by several injections of OT lost their ability to produce detectable amounts of endogenous pyrogen (EP) in response to the specific agent (OT) but mobilized normal amounts of EP when given a small unrelated stimulus. On the other hand, when this stimulus followed shortly after an initial tuberculin fever of sufficient magnitude, release of additional EP was suppressed, presumably due to an inhibitory effect of the EP previously mobilized by tuberculin.

Similarly, a single large dose of endotoxin almost completely suppressed the response of sensitized rabbits to OT given several hours later. Since several spaced injections of the same dosage were ineffective, this phenomenon does not appear to be attributable to the known mechanisms by which endotoxins promote non-specific resistance to toxicity and infection. Tolerance to tuberculin could not be definitely shown following an injection of Newcastle disease virus which also produces a circulating EP, and it has been inferred that endotoxin blocks the pyrogenic action of antigen on host tissues directly rather than through mobilizing EP.

On the basis of these observations, the relationship of specific to non-specific tolerance to tuberculin fever has been compared in terms of the ability of such tolerant animals to mobilize EP to heterologous stimuli and it is concluded that the two forms of tolerance are different. Furthermore, the fact that a number of unrelated agents produce tolerance non-specifically supports the concept that there may be a common source of EP released by a number of stimuli, including endotoxins and myxoviruses, as well as antigen in specifically sensitized hosts.
THE VACUOLATING VIRUS OF MONKEYS
Authors: Hsiung G.-D. , Gaylord W. H.
Published: June 2004

A vacuolating virus isolated from uninoculated patas monkey kidney cultures was found to be serologically identical with SV40, a virus previously found in association with rhesus and cynomolgus monkeys. Detection of the patas virus was facilitated when patas cells were exposed to x-ray treatment. Rhesus monkey and human cells were relatively insusceptible to the virus, although it persisted in these cells for a long period of time. Distinct intranuclear inclusions were detected in infected patas cultures 2 to 3 days before cytoplasmic vacuoles were noticeable. Cultures previously infected with PA-57 virus did not affect yields of poliovirus, and doubly infected cells were easily distinguished in stained preparations.