bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ANALYSIS OF STREPTOCOCCAL INFECTIONS
Authors: Halbert S. P. , Bircher R. , Dahle E.
Published: June 2004

1. The rapid death which occurred after intravenous injection of activated streptolysin O from. Group A or Group C streptococci was always preceded by profound electrocardiographic alterations. After several multiples of the LD50 doses, cardiac electrical arrest or fibrillation could occur within 2 to 4 seconds after completion of the injection.

2. The streptolysin O preparations used were rather highly purified, but were known to be contaminated with small amounts of one or two other immunologically distinct components. Evidence that the observed results were due to streptolysin O was obtained by tests of the reversibly oxidized materials, and by cholesterol inactivation, as well as by in vivo protection with human gamma globulin rich in antistreptolysin antibodies.

3. Four non-streptolysin streptococcal antigens, partially or highly purified, failed to produce similar electrocardiographic changes, and were much less toxic. One of these was 3 X recrystallized and 1 X rechromatographed streptococcal proteinase. Shigella paradysenteriae type III endotoxin also did not produce striking electrocardiographic abnormalities.

4. A working hypothesis has been developed implicating streptolysin O as the etiological streptococcal factor responsible for the pathogenesis of rheumatic fever, which seems to account for the principal features of this illness.
PATHOGENICITY FOR SUCKLING MICE OF COXSACKIE VIRUSES ADAPTED TO HUMAN AMNION CELLS
Authors: Lehmann-Grube Fritz , Syverton Jerome T.
Published: June 2004

Continuous passages in primary human amnion cell cultures of Coxsackie prototype viruses A-9, A-10, A-11, A-13, A-14, A-15, A-18, B-1, B-2, B-4, and B-5 increased the titers, hastened and enhanced cytopathic effect, and in varying degrees caused loss of virulence for newborn mice. Only B-3 behaved differently in that neither adaptation to cells in vitro nor attenuation with respect to the original animal host could be observed. Types A-15, B-1, B-2, and B-5 slowly regained virulence when passed in mice after high concentration passages in amnion cells whereas all other viruses reverted to their original virulence after only 1 or 2 passages in the animal host. When these strains, however, were purified by cloning procedures, they too showed markedly increased stability. In all stages of attenuation, viruses multiplied extensively in vivo as could be shown by titration in amnion cell cultures. It is suggested that a genetic mechanism is operative leading to virus populations in which the majority of the particles is qualitatively changed.
EXPERIMENTAL GLOMERULONEPHRITIS
Authors: Dixon Frank J. , Feldman Joseph D. , Vazquez Jacinto J.
Published: June 2004

Daily injections of any one of several foreign serum proteins produced in rabbits functional and morphological alterations similar to those seen in acute, subacute, and chronic human glomerulonephritis. The critical factor determining whether a rabbit would develop renal disease and the type of disease developed was the amount of antibody the rabbit formed. Those responding with much antibody were likely to develop an acute, self-limited glomerulonephritis and to be subsequently immune to further renal damage. Those responding with antibody barely sufficient to neutralize the antigen injected developed subacute and chronic glomerulonephritis. In the circulation of the rabbits with chronic glomerulonephritis, there was a daily recurring antigen-antibody reaction in the region of near antigen excess to near antibody excess which presumably led to the disease. Antigen apparently in the form of antigen-antibody complexes was deposited along the renal capillary basement membranes coincident with the development of subacute and chronic glomerulonephritis. Once developed, the morphologic stigmata of chronic glomerulonephritis persisted even after injections of antigen were stopped. However, in milder instances the renal function recovered in part after stopping antigen.

This experimental model has several implications: first, the renal injury is precipitated by antigens with no known affinity for, or immunologic relationship to, kidney; second, antigen antibody complexes localize in the kidney, apparently on the basis of non-immunologic factors, and may be an etiologic agent of renal injury; third, severe hypersensitivity disorders can be related specifically to relatively poor as well as to good antibody responses; and finally, the pathogenesis suggested here offers an alternative to that of nephrotoxic serum nephritis for the experimental approach to the study of human glomerulonephritis.
THE CHANGES IN SERUM PROTEINS AND BLOOD VOLUME DURING IMMUNIZATION
Authors: Bjørneboe M. , Jarnum Stig
Published: June 2004

In rabbits hyperimmunized with pneumococcal vaccine high concentrations of gamma globulin are produced. In such rabbits, plasma volume was determined with 131I-labelled rabbit albumin and red cell volume with 51-Cr-labelled autologous red cells. It was found that the plasma volume increased with increasing gamma globulin concentration, the highest values observed being about 10 gm. per cent gamma globulin and about 70 ml. plasma per kg as against normal values of 0.6 to 0.7 gm. per cent gamma globulin and 30 ml. plasma per kg. The red cell volume was the same in immunized and in normal rabbits and consequently hemoglobin concentration fell with increasing gamma globulin.
IMMUNOLOGIC STUDIES WITH ETHYLENE OXIDE-TREATED HUMAN SERUM
Authors: Maurer Paul H.
Published: June 2004

The antigenicity of an ethylene oxide-treated human serum in humans has been studied. The immune response to the material had many of the characteristics of a delayed cellular skin reaction. Even after repeated immunizations by intradermal skin testing over a period of 1½ years, no detectable antibody could be found in the sera. The antigenicity has been shown to be associated with drastic alteration of the homologous serum proteins as evidenced by (a) the formation of new proteins, and (b) the poor cross-reactions of the modified serum proteins with antisera against normal human serum albumin and normal human gamma globulin.

The delayed hypersensitivity was transferable to normal recipients by either viable or killed leukocytes. The implications of these findings have been discussed with respect to the problem of sterilization of sera, the tuberculin reaction, and autoimmune phenomena.
ANTIGENICITY OF RAT COLLAGEN
Authors: Rothbard Sidney , Watson Robert F.
Published: June 2004

Rabbit serum or globulin, containing antibody to rat collagen, injected intravenously or intracardially into normal or adjuvant-prepared rats becomes fixed in the basement membranes of renal glomeruli and, to a slight extent, of the tubules. When examined by ultraviolet light, this antibody can be identified in tissue sections by the yellow-green fluorescence occurring where the rabbit globulin, associated with the fixed collagen antibody, has reacted with fluorescein-conjugated anti-rabbit globulin from ducks. The reaction of the antibody to rat collagen with its antigen in the kidney is a primary factor in the production of the renal glomerular injury which occurs in rats prepared with adjuvant. Adjacent control sections failed to fluoresce when pretreated with unlabeled anti-rabbit globulin or when treated with heterologous conjugated anti-duck globulin from rabbits. The antibody to rat collagen remains in the kidney as long as 92 days and has been detected as early as 45 minutes after injection. When normal rabbit serum, rabbit anti-fish collagen serum, or rabbit anti-rat collagen serum absorbed with rat collagen was substituted for the rabbit anti-rat collagen serum, fixed antibody could not be demonstrated by fluorescence; but absorption of the anti-rat collagen serum with fish collagen did not affect the antibody fixation.

This series of immunologic tests indicates that the anti-collagen serum reacts with its homologous antigen, presumably collagen, in the basement membranes of renal glomeruli and tubules, and that specific antibody can be used to identify collagen in other tissues of the animal body.
STUDIES ON BACTERIEMIA
Authors: Derby Bennett M. , Rogers David E.
Published: June 2004

Observations are presented on the course of experimental bacteriemia in rabbits modified by thorotrast reticuloendothelial "blockade" and mechlorethamine induced leukopenia, given singly and together.

The production of severe granulocytopenia did not impair the clearance of staphylococci from the blood stream and did not enhance the impairment of clearance produced by thorotrast reticuloendothelial "blockade."

Neither severe granulocytopenia nor thorotrast blockade alone produced consistent impairment in the removal of circulating E. coli from the blood stream, whereas when these conditions were present together, the early phases of clearance in these animals were virtually prevented.

These results indicate that the host mechanisms operative in the control of bacteriemia differ for staphylococci and E. coli. It is suggested that the fate of bacteria within polymorphonuclear leukocytes may in part determine the importance of these cells in the removal of bacteria from the blood stream.
BLOOD GROUP ACTIVITY OF GRAM-NEGATIVE BACTERIA
Authors: Springer Georg F. , Williamson Peter , Brandes William C.
Published: June 2004

Distribution of blood group A, B, and H(O) activities among 282 aerobic Gram-negative bacteria, many isolated from the blood of patients, has been studied. Almost half of these bacteria were found to be blood group active. About 10 per cent of the organisms exhibited high, disproportional activities, which in some instances approached those of crude human blood group mucoids. No significant, specific D (Rho), M, or N activity was found in approximately 70 members of the Enterobacteriaceae.

An attempt was made to correlate the observed activity of a given organism of known O somatic antigen with its monosaccharide components. The presence of those sugars which account for the specificity of human blood group mucoids was noted.

The bearing of these findings on the origin of human anti-A and anti-B isoantibodies has been mentioned.
ENDOTOXIN FEVER IN GRANULOCYTOPENIC ANIMALS
Authors: Herion John C. , Walker Richard I. , Palmer Jeffress G.
Published: June 2004

The febrile response to bacterial endotoxin was measured in rabbits made leukopenic with nitrogen mustard. A striking increase in susceptibility to the lethal effects of endotoxin occurred in severely leukopenic animals. Animals without circulating granulocytes, or with only basophils, developed no significant fever after endotoxin injection. Animals with circulating granulocytes other than basophils exhibited a biphasic febrile response to endotoxin; this response was significantly less in magnitude than that of control animals. Control animals, severely granulocytopenic animals, and animals with no circulating granulocytes other than basophils showed comparable febrile responses to serum pyrogen.

These results suggest that granulocytes inactivate endotoxin in vivo and support the hypothesis that leukocyte pyrogen is a necessary intermediate in endotoxin fever. Basophils do not appear to participate in this process. These observations also contradict previous studies that were taken to indicate a normal febrile response to endotoxin in leukopenic animals and suggest that those results are related to the persistence of granulocytes.
THE SPECIFICITY OF THE PASSIVE HEMAGGLUTINATION METHODS USED IN SEROLOGY OF TUBERCULOSIS
Authors: Takahashi Yoshio , Fujita Seiichi , Sasaki Akio
Published: June 2004

The Middlebrook-Dubos hemagglutination test with normal red cells and the Boyden hemagglutination test with red cells tanned with tannic acid were shown to be strictly specific, for tubercle polysaccharide and for the protein antigens. The former test detects polysaccharide antibodies and the latter protein antibodies. Convincing evidence is given that polysaccharide does not adhere to the surface of tanned red cells nor protein to the normal red cell surface. Hemosensitizing ability and in vitro antigenicity were found to be two distinct properties of tubercle polysaccharide and protein antigens.

The phosphatide hemagglutination test with normal red cells sensitized with tubercle phosphatide is also specific; it detects only phosphatide antibodies.

The three different kinds of antibodies, antipolysaccharide, antiprotein, and antiphosphatide, were shown to be completely distinct from each other in tuberculous serum. Each of them can be completely removed from serum by absorption with red cells or kaolin particles coated with its corresponding antigen.

The reliability of the cross-inhibition test is discussed.
STUDIES ON CELL LINES DEVELOPED FROM THE TISSUES OF PATIENTS WITH GALACTOSEMIA
Authors: Krooth Robert S. , Weinberg Arnold N.
Published: June 2004

Cell lines were developed from biopsies on galactosemic and non-galactosemic patients. It was shown that one can discriminate between lines from the two types of donors by their relative growth in glucose and galactose and by their ability to oxidize galactose-1-C14. The latter method was successful in distinguishing a heterozygous cell line from the normal ones. Sensitivity of galactosemic cells to galactose was suggested by some of the experiments. The kinetics of growth were in some ways reminiscent of a similar phenomenon in the transferase mutants of E. coli, though in the human cells the effect was much less marked.
THE RENAL LESIONS OF ELECTROLYTE IMBALANCE
Authors: Holliday Malcolm A. , Bright Nancy H. , Schulz Dale , Oliver Jean
Published: June 2004

Acute chloride depletion in rats is associated with the occurrence of an extensive cell damage in the mid-portion of the proximal convolutions which is followed by an excessive hyperplastic reaction of the renal epithelium; no other significant lesions were found by microdissection in either the tubules of the nephrons or the collecting system.

Potassium deficiency is not essential to the development of this lesion but does increase the severity of the reaction.

As in the case of potassium deficiency, chloride depletion predisposes to or exaggerates the structural alterations that accompany excess phosphate intake.

The relations of the different structural changes in renal architecture that occur in various states of electrolyte imbalance are discussed as well as the relation of the lesions seen experimentally in the rat and monkey and clinically in man.
THE ISOLATED PERFUSED BOVINE LIVER
Authors: Chapman Niles D. , Goldsworthy Patrick D. , Volwiler Wade , Nyhus Lloyd M. , Martinis Andrew J.
Published: June 2004

1. A procedure is described for surgically isolating and artificially perfusing the liver of the young bovine. Heparinized autogenous blood from the hepatectomized animal diluted with Krebs-Ringer-bicarbonate solution is employed as the perfusate.

2. This preparation has been satisfactorily reproducible in this laboratory in more than 90 separate sequential perfusions. Absence of a sensitive hepatic venous smooth musculature contributes to the ability to maintain satisfactory perfusion for as long as 24 hours.

3. The perfusate was usually maintained bacterially free for at least the first 12 hours of perfusion without the use of antibiotics. The perfusate was maintained at normal body temperature and, by varying the CO2 content of the oxygenating gas, within a physiological pH range. The importance of these features when studying problems of intermediary biochemistry and ultrastructure is emphasized.

4. The liver of the bovine calf is sufficiently large to permit (a) simultaneous and independent perfusion through the hepatic artery and portal vein, and (b) repeated sampling of hepatic tissue without interruption of the circulation.

5. Excellent, viable condition of the isolated liver, throughout many hours of perfusion, was demonstrated by steady state of oxygen consumption, efficient clearance of bromsulphalein dye, continuous secretion of bile, constancy of blood flows and pressures, and very minimal alterations from normal in histologic and ultrastructural detail.
DEMONSTRATION OF THE SEQUENTIAL DEVELOPMENT OF VACCINIAL ANTIGENS AND VIRUS IN INFECTED CELLS: OBSERVATIONS WITH CYTOCHEMICAL AND DIFFERENTIAL FLUORESCENT PROCEDURES
Authors: Loh Philip C. , Riggs John L.
Published: June 2004

Virus-induced alterations in vaccinia virus-infected HeLa cells have been followed by immunofluorescent and cytochemical techniques. In a time sequence study, infected cells show an early increase in cytoplasmic RNA content, followed by appearance of centers of viral DNA synthesis in the cytoplasm. The centers of synthesis were detected at 4 hours post infection, with the acridine orange fluorochrome stain as compared to 6 hours with Feulgen and methyl green-pyronin stains. Marginal fragmentation of the inclusion bodies was seen at 8 to 10 hours post infection, and appears to coincide with the first increase in cell-associated virus.

With the immunofluorescent technique, it was found that the LS antigen of the virus can be detected at about 4 hours post infection. This is followed at 5 to 6 hours post infection by the appearance of the NP antigen. Both antigens are found only in the cytoplasm, and precede the appearance of the infective particle. The HA antigen, a by-product of virus-cell interaction, is not seen until about 10 hours post infection; that is, several hours after the appearance of both the LS and NP antigens, and only after the appearance of mature virus.

The successful application of the use of two immune sera, each labeled with a different fluorescent dye for the simultaneous visualization of two antigens within a cell, is reported. Using this technique, the sites of LS and NP antigen synthesis, were easily differentiated. The intimate mixing of the two antigens at a later stage appears to coincide with the fragmentation of the inclusion body and the first detectable increase in cell-associated virus. The evidence obtained strongly suggests that the typical inclusion body observed in vaccinia-infected cells is composed mainly of the NP antigen.
STUDIES ON TUBERCLE BACILLUS-MONOCYTE RELATIONSHIP
Authors: Fong Jacob , Chin Dennis , Elberg Sanford S.
Published: June 2004

Passage of the virulent H37Rv strain of tubercle bacillus in normal or immune systems (normal or immune monocytes suspended in the corresponding serum) resulted in decreased virulence of the bacilli; this was evidenced by the very low mortality rates in mice inoculated intravenously with passaged bacilli.

Passaged bacilli when cultivated directly in tween-albumin medium or when grown on glycerol-blood agar plates after recovery from infected mouse tissues proved as virulent as unpassaged bacilli.

The decreased virulence of passaged H37Rv was accompanied by loss of ability to bind neutral red.

Passaged H37Rv was more sensitive than unpassaged bacilli to inactivation by sodium oleate and by normal monocyte lysate; however, passaged H37Rv was more resistant than unpassaged bacilli to inhibition by streptomycin.
EFFECTS OF CHRONIC EXCESS SALT FEEDING
Authors: Dahl Lewis K.
Published: June 2004

Hypertension was induced in female rats by chronic feeding of sodium-containing salts in excess. The hypertension so induced appeared to be self-sustaining since about two-thirds of the animals failed to show a significant fall in blood pressure after withdrawal of these salts from the diet.

Under the conditions of these experiments a lack of response to restriction of dietary sodium does not exclude an etiologic relationship between salt intake and development of hypertension.
SPECIFICITY OF THE REACTION BETWEEN RHEUMATOID FACTORS AND GAMMA GLOBULIN
Authors: Fudenberg Hugh H. , Kunkel Henry G.
Published: June 2004

Rheumatoid factors in the sera of patients with rheumatoid arthritis appear to be specifically directed against genetically determined "antigens" in human γ-globulin. At least eight rheumatoid factors of differing specificity exist; usually several are present in combination in the same serum. The different rheumatoid factors can be readily detected through their pattern of reactivity with anti-Rh antibodies from different individuals. Rheumatoid factors in diseases other than rheumatoid arthritis were found to have a more restricted specificity, contrasted to the broader reactivity of the factors in most rheumatoid arthritis sera. A specificity similar to that for incomplete antibodies was not demonstrated for the reaction of rheumatoid factors with aggregated γ-globulin or with γ-globulin to form the "22S complex."

In certain instances, using the anti-Rh system, rheumatoid factors were found to react poorly with the patient's own γ-globulin, compared to that of other individuals of different genetic γ-globulin types. These results, as well as additional indirect evidence, indicate that the rheumatoid factors can possess isospecificity. However, a certain degree of autospecificity was also found which was most clearly evident through complex formation with the patients own γ-globulin and in the reaction with aggregates. The relevance of these findings to possible isoantibody as well as autoantibody concepts is discussed.
INDUCTION OF TUMORS IN DOMESTIC RABBITS WITH NUCLEIC ACID PREPARATIONS FROM PARTIALLY PURIFIED SHOPE PAPILLOMA VIRUS AND FROM EXTRACTS OF THE PAPILLOMAS OF DOMESTIC AND COTTONTAIL RABBITS
Authors: Ito Yohei , Evans Charles A.
Published: June 2004

A deoxyribonucleic acid preparation which showed infectivity and tumorigenic activity in domestic rabbits was isolated from the papillomatous tissue of wild cottontail rabbits by phenolic deproteinization procedure. The activity of the preparation could be completely abolished by its exposure to a minute amount (0.02 µg/ml) of DNAase. Antisera against Shope papilloma virus did not block the tumorigenic activity of the preparation, and trypsin and chymotrypsin had no effect on it. The extraction with phenol of a partially purified virus preparation also yielded extracts with tumorigenic potency.

Extracts obtained from the domestic rabbit papilloma and submitted to phenolic deproteinization also proved infective and tumorigenic in rabbits of this sort, although the level of "tumorigenicity" was much lower than that of the cottontail preparations. Tests for intact virus, carried out with half of the extracts yielded wholly negative findings.
STUDIES ON THE PATHOGENESIS OF ACUTE INFLAMMATION
Authors: Allison Fred , Lancaster Margie G.
Published: June 2004

Vigorous anticoagulation with heparin sodium and sodium warfarin singly and in combination did not prevent the margination and endothelial sticking reaction of leucocytes in rabbit ear chambers damaged by heat. The general inflammatory reaction observed in this preparation was similarly uninfluenced by the anticoagulants. An unexpected finding after administration of heparin was the enhanced formation of platelet and fibrin-like thrombi within damaged ear chambers. Sodium warfarin did not induce or prevent this heparin effect. Production of these heparin-associated thrombi was minimized in animals subjected to defibrinogenation in vivo whereas leucocytic sticking was not modified. Although defibrinogenation was not absolute, these experiments represent additional proof that the sticking of white blood cells to vascular endothelium is not causally related to the fibrinogen-fibrin system.
PREPARATION AND HOST-REACTIVE PROPERTIES OF ENDOTOXIN WITH LOW CONTENT OF NITROGEN AND LIPID
Authors: Ribi Edgar , Haskins Willard T. , Landy Maurice , Milner Kelsey C.
Published: June 2004

Endotoxins of low lipid content prepared from S. enteritidis by the aqueous ether method have been further treated to remove bound lipid by non-hydrolytic procedures. Such endotoxins, containing as little as 2 per cent lipid A, were as potent in stimulating a variety of physiological responses as those prepared by the well known phenol-water or Boivin procedures which yield products containing as much as 30 per cent lipid A.

To verify the difference in lipid content between the aqueous ether preparations and other types of endotoxins, three different methods of lipid analysis were employed: determination of chloroform-soluble material released by hydrolysis with hydrochloric acid (lipid A) or with acetic acid (lipid W), and estimation of total bound fatty acids. These methods were in accord in showing the magnitude of the difference. No more than one-half of the fatty acids present in endotoxin were associated with the fraction designated lipid A.

Methods are described for the preparation of potent endotoxins with analytical values for nitrogen, phosphorus, hexosamine, carbohydrate, and fatty acid which do not differ appreciably from those of the classical, non-toxic, haptenic polysaccharides.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Gillman Samuel M. , Bornstein Donald L. , Wood W. Barry
Published: June 2004

Rabbits made granulocytopenic with nitrogen mustard have been shown to generate serum endogenous pyrogen when given a fever-producing dose of bacterial endotoxin. This finding is in accord with the hypothesis that endogenous pyrogen plays a central role in the pathogenesis of endotoxin fever. The fact that leucopenic animals produce less serum-endogenous pyrogen than normal animals given the same dose of endotoxin has also been confirmed and suggests that polymorphonuclear leucocytes constitute a major source of the endogenous pyrogen which is demonstrable in the circulation during endotoxin fever.
EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM
Authors: Berry L. Joe , Smythe Dorothy S.
Published: June 2004

In vitro secretion of glycocorticoids by adrenal glands pooled from several control mice was compared with that of glands removed from animals following injections of either ACTH or endotoxin. Both substances prevent glycocorticoid synthesis stimulated in vitro with ACTH. Cholesterol content of adrenal glands under these conditions was nearly depleted, indicating maximal response to ACTH or endotoxin prior to their removal for the in vitro tests.

In an effort to account physiologically for the manner in which endotoxin suppresses or prevents the rise in urinary nitrogen excreted in response to ACTH, blood non-protein nitrogen levels (NPN) were determined. The following experimental conditions resulted in increased urinary nitrogen excretion but did not alter blood NPN: cortisone given alone or at the same time as endotoxin; ACTH alone; dichloroisoproterenol (DCI) given concurrently with endotoxin; and lactalbumin digest injected intraperitoneally. Increases (2- to 3-fold) in blood NPN were observed when endotoxin was given alone, concurrently with ACTH, or 3 hours prior to cortisone, DCI, or lactalbumin digest. Urinary nitrogen excretion showed no change under these conditions.

The elevation in blood NPN in endotoxin-poisoned mice was found to be due almost entirely to urea nitrogen and not to amino acid nitrogen or to other nitrogenous wastes.

Blood clearance of mulin, phenol red excretion, and urea elimination were each determined in control and in endotoxin-poisoned mice. The latter mice showed impaired renal function. Treatment with diuretics (diuril and aminophylline) failed to alter oliguria or elevated blood NPN. Hydergine treatment was also without effect.

Total carcass NPN and urinary nitrogen excretion data were combined to give a picture of total protein catabolized by mice under different experimental conditions. Cortisone injected at the same time as endotoxin or 3 hours later resulted in the same increase in total NPN. However, in the former case all the extra nitrogen appeared in the urine while in the latter it remained in the carcass. ACTH given alone or concurrently with endotoxin produced large increases in total NPN but less in poisoned mice. This suggests that endotoxin suppresses adrenal response to ACTH.

Urea injected into normal mice was recovered quantitatively in urine while in endotoxin-poisoned mice it was partitioned between carcass and urine. Elevation of carcass NPN by means of urea injections failed to alter the lethality of an LD70 dose of endotoxin.
THE INDUCTION OF A RHEUMATOID FACTOR-LIKE SUBSTANCE IN RABBITS
Authors: Abruzzo John L. , Christians Charles L.
Published: June 2004

Hyperimmunization of two groups of rabbits with killed Escherichia coli and Bacillus subtilis has resulted in the formation of a serum factor (RFLS) which resembled the human rheumatoid factor. It was a heat-stable protein that migrated electrophoretically in the gamma-beta globulin range and sedimented rapidly with ultracentrifugation. The serologic properties of the RFLS were destroyed by mercaptoethanol. It reacted primarily with rabbit gamma globulin in an aggregated state (immune complexes or physically aggregated gamma globulin) and demonstrated cross-reactivity with human gamma globulin.
THE APPLICATION OF FERRITIN-CONJUGATED ANTIBODY TO ELECTRON MICROSCOPIC STUDIES OF INFLUENZA VIRUS IN INFECTED CELLS
Authors: Morgan Councilman , Hsu Konrad C. , Rifkind Richard A. , Knox Alice W. , Rose Harry M.
Published: June 2004

Immersion of chorioallantoic membranes infected by influenza virus in ferritin-conjugated antibody globulin prior to fixation permits recognition of viral antigen at the cellular surface. In some cases the antigen is confined to sites at which viral particles appear to be in process of release, whereas in others it is present along the entire cellular surface. During infection part or all of the cellular membrane presumably is transformed so that it contains the antigenic and structural components which coat the virus during emergence. It is suggested that detached fragments of cytoplasm possessing surface hemagglutinin but incapable of initiating infection constitute at least one form of "incomplete virus."
ANTIBODY FORMATION IN VITRO
Authors: Fishman M.
Published: June 2004

Neutralizing activity against T2 bacteriophage appeared in cultures of lymph node cells from normal rats in response to their in vitro stimulation with a cell-free filtrate derived from homogenized rat macrophages which had been incubated with T2 bacteriophage.

This activity was specifically directed against T2 bacteriophage. It resided in a fraction of the culture fluid which had the salting-out properties of serum globulin. Phage neutralization was inhibited by antibody specific for rat serum gamma globulin.

Antibody production against T2 bacteriophage in cultures of lymph node cells from normal animals failed to occur if (a) T2 bacteriophage alone was added, (b) if the incubation period of macrophages and T2 phage was unduly shortened, (c) if the cell-free filtrate was heated at 80–100°C for 15 minutes, (d) if more than an optimal amount of T2 bacteriophage was added to the macrophages. Additional factors which prevented the formation of antibody were the heat inactivation of the lymph node cells or the addition to the culture medium of either streptomycin or ribonuclease. Finally, it was found that macrophages and lymph node cells had to be obtained from animals of one and the same species.

All essential findings on the production of antibody to T2 bacteriophage in vitro could be confirmed by substitution of the chick embryo for the tissue culture medium.

The results are discussed in terms of a possible mechanism of antibody production in which an RNAse-sensitive substance resulting from the interaction of macrophages and antigen is capable of stimulating antibody synthesis in lymphocytic cells.
EFFECTS OF BACTERIAL ENDOTOXIN ON RABBIT PLATELETS
Authors: Des Prez Roger M. , Horowitz Herbert I. , Hook Edward W.
Published: June 2004

Incubation of platelet-rich rabbit plasma with E. coli endotoxin at 37°C results in platelet aggregation and transfer of platelet 5-hydroxytryptamine to plasma. Release of 5HT is influenced by dose of endotoxin, type of anticoagulant, and temperature of incubation. A heat-labile plasma factor is necessary for the platelet-endotoxin interaction. Additional studies have shown that incubation of endotoxin with platelet-rich rabbit plasma also results in release of platelet phospholipid and bactericidins active against B. subtilis.
INHIBITION OF RED CELL SEQUESTRATION BY CORTISONE
Authors: Kaplan Manuel E. , Jandl James H.
Published: June 2004

The effect of cortisone on the sequestration of (a) antibody-coated red cells and (b) incubated red cells was studied in rats. Cortisone administration inhibited the hepatic sequestration of red cells altered by non-immune as well as by immune injury. There was a latent period of 2 days between the institution of cortisone therapy and its first manifest effect on hepatic sequestration.

The splenic sequestration of altered red cells was not inhibited by cortisone, and there was no inhibition of the sequestration of hemoglobin by either liver or spleen.

It is suggested that steroids may inhibit hepatic sequestration through hemodynamic effects.
THE USE OF SPECIFIC "LYMPHOCYTE" ANTISERA TO INHIBIT HYPERSENSITIVE REACTIONS OF THE "DELAYED" TYPE
Authors: Waksman Byron H. , Arbouys Simone , Arnason Barry G.
Published: June 2004

Rabbit antisera against normal guinea pig lymph node, when injected into guinea pigs, produced transient depression of the level of blood lymphocytes. It had no effect on other circulating cellular elements. Repeated injection over several days produced lymphopenia, which became progressively less marked with continued treatment, and clear-cut depletion of small lymphocytes in lymph nodes, whether draining an inoculation site or remote. In guinea pigs treated with lymphocyte antiserum, there was marked suppression of the tuberculin and contact allergic reactions and the "delayed" skin reaction to purified diphtheria toxoid, and a relative suppression of allergic encephalomyelitis and the rejection of first set skin homografts. There was a slight effect on second set graft rejection and no effect on PCA or the reversed passive Arthus reaction. Non-specific reactions to intradermal turpentine or to concentrated dinitrochlorobenzene placed on the skin were moderately reduced. The suppression of these reactions (except allergic encephalomyelitis) was closely correlated with the degree of lymphopenia. Lymphocyte antiserum absorbed with normal blood white cells lost both its lymphopenic effect and its ability to suppress the tuberculin reaction. It is tentatively concluded that a circulating mononuclear cell, probably the small lymphocyte, is the primary reactant in the various types of delayed hypersensitive reactions.
THE AMELIORATION OF HYPERVITAMINOSIS D IN RATS WITH VITAMIN A
Authors: Clark Irwin , Bassett C. Andrew L.
Published: June 2004

The administration of relatively large amounts of vitamin A to hypervitaminotic D rats decreases the toxicity of this condition as evidenced by increased longevity, better weight gain, decreased soft tissue calcification and by considerable improvement in the histologic appearance of osseous structures.
IMMUNOLOGICAL DETERMINANTS OF POLYOMA VIRUS ONCOGENESIS
Authors: Habel Karl
Published: June 2004

Adult mice and hamsters can be made resistant to an isologous transplantable polyoma tumor by an inapparent infection with polyoma virus. This resistance is cell-mediated and seems not to be related to anti-viral serum antibodies. The basis of the resistance appears to be a transplantation type of cellular immunity directed against a "foreign" antigen contained in the tumor cell. Evidence has been presented to demonstrate this tumor antigen. It is possible that this phenomenon may explain the lack of oncogenesis by polyoma virus infection of adult mice, and the rarity of naturally occurring polyoma tumors.
SENSITIZATION TO DENATURED AUTOLOGOUS GAMMA GLOBULIN
Authors: McCluskey Robert T. , Miller Frederick , Benacerraf Baruj
Published: June 2004

Immunization of guinea pigs with denatured autologous gamma globulin results in the development of delayed hypersensitivity to some form of gamma globulin. When the autologous gamma globulin is subjected to denaturation with alkaline treatment as employed in this study, guinea pigs regularly develop reactivity to the immunizing material and occasionally to some form of heterologous gamma globulin. With other forms of denaturation, such as produced by urea, ultrasound, or heat, guinea pigs rarely develop sensitivity to the immunizing material but frequently exhibit delayed reactivity to native or denatured heterologous gamma globulin. Reactivity against native autologous gamma globulin does not occur. Guinea pigs immunized with undenatured autologous gamma globulin fail to develop reactivity to any form of gamma globulin.

Rabbits immunized with denatured autologous gamma globulin develop circulating antibodies against some form of gamma globulin. Rabbits immunized with alkaline denatured autologous gamma globulin develop antibodies against the preparation used for immunization and against heterologous gamma globulin; rabbits immunized with autologous gamma globulin subjected to freeze-thaw or heat denaturation develop antibodies against heterologous globulin, but antibodies against the immunizing material can only rarely be demonstrated.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Kaiser Hans Klaus , Wood W. Barry
Published: June 2004

Determination of the dose-response curve for rabbit leucocytic pyrogen reveals a hyperthermic "ceiling" at which there is a marked insensitivity to dosage. This finding has important implications in relation to the quantitative assay of leucocytic pyrogen.

Polymorphonuclear leucocytes separated from normal rabbit blood possess the capacity to produce less than 5 per cent of the pyrogen generated by the same number of rabbit granulocytes collected from acute peritoneal exudates.

Blood granulocytes, separated in the cold from the buffy coat, contain no detectable preformed pyrogen.

The amount of preformed pyrogen within exudate granulocytes represents but a small fraction of the pyrogen which the cells are capable of generating when incubated in normal saline at 37°C. It is suggested that the active pyrogen is formed from an inactive precursor within the cells.

Under the conditions tested, cell fragments of rabbit granulocytes fail to produce endogenous pyrogen.

The fact that the production of pyrogen is blocked at 4°C is in keeping with the hypothesis that it involves metabolic reactions within the cell.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Kaiser Hans Klaus , Wood W. Barry
Published: June 2004

The production of endogenous pyrogen by intact granulocytes obtained from acute peritoneal exudates is blocked by arsenite, iodoacetate, p-chloromercuribenzoate, and N-ethylmaleimide in concentrations of 2 x 10–4 M.

When the concentration of these sulfhydryl-reactive enzyme inhibitors is increased to 2 x 10–2 M, only the iodoacetate inactivates the pyrogen molecule, whereas the arsenite, the p-chloromercuribenzoate, and the N-ethylmaleimide have no gross effect upon its thermogenic activity.

Both diisopropyl fluorophosphate and dinitrofluorobenzene are even more potent inactivators of the pyrogen molecule than iodoacetate, although the action of the DFP cannot be blocked or reversed by known antagonists such as 2-pyridine aldoxime methiodide and hydroxylamine.

Proteolytic enzymes, potentially capable of degrading leucocytic pyrogen, are released from polymorphonuclear leucocytes, along with the pyrogen, when the cells are incubated in normal salt solution. These enzymes are readily activated by a sufficient concentration of glutathione (2 x 10–2 M). They are not present in preparations of partially purified leucocytic pyrogen from which much of the non-pyrogenic protein has been removed.

Glutathione by itself, even at concentrations as high as 2 x 10–1 M, does not affect in the gross the thermogenic activity of the purified pyrogen.

The implications of these findings in relation to both the production and the chemical characteristics of leucocytic pyrogen are discussed.
STUDIES ON THE CHEMICAL STRUCTURE OF THE STREPTOCOCCAL CELL WALL
Authors: Krause Richard M. , McCarty Maclyn
Published: June 2004

The trypsinized cell walls of Group C streptococci contain two components, the group-specific carbohydrate and a mucopeptide polymer. Hot formamide extraction of Group C cell walls results in a soluble group-specific carbohydrate fraction and an insoluble mucopeptide residue. This mucopeptide, similar in composition to that of Groups A and A-variant streptococci, contains N-acetylglucosamine, N-acetylmuramic acid, alanine, glutamic acid, lysine, and glycine. It is dissolved by the muralytic enzymes, including lysozyme, which does not attack the whole cell wall. Lysis of the cell wall by phage-associated lysin results in the release of soluble fragments composed of the elements of mucopeptide.

Group C carbohydrate extracted with formamide is composed primarily of N-acetylgalactosamine and rhamnose. Serological studies suggest that the specificity of Group C carbohydrate is determined by the N-acetylgalactosamine.
STUDIES ON THE TRANSFERRINS OF ADULT SERUM, CORD SERUM, AND CEREBROSPINAL FLUID
Authors: Parker W. Carey , Bearn Alexander G.
Published: June 2004

Nine of the twelve known variants of human transferrin have been resolved by the action of neuraminidase into stepwise patterns of four additional slower moving components whose relative intensities depended upon the concentration of enzyme. These components appeared to represent the stepwise removal of the four sialic acid residues from the transferrin molecule, and at large enzyme concentrations, almost all of the transferrin was reduced to the position of the slowest moving component. In contrast, the electrophoretic mobilities of haptoglobin, ceruloplasmin, and α2-macroglobulin showed a gradual decrease with increasing neuraminidase concentration.

The transferrins of chimpanzees, rhesus and cynomolgus monkeys, and cattle were resolved by neuraminidase into two slower moving components. These experiments suggested that the primate and cattle transferrins contained only two sialic acid residues accessible to the enzyme.

Transferrins C, B2, and D1 and a cynomolgus monkey transferrin were purified from serum by starch block electrophoresis and cellulose chromatography. Ultracentrifugal analysis could detect no difference in sedimentation rate between transferrin C, the primate transferrin, and neuraminidase-treated transferrin C. The human transferrins showed no variation in amino acid composition, but the cynomolgus transferrin was approximately 20 per cent higher in serine content and 50 per cent lower in glucosamine than human transferrin C. Reactions of antigenic identity were obtained among five human transferrin variants but a reaction of only partial identity was obtained between transferrin C and the cynomolgus transferrin.

The transferrin pattern of cord blood showed a prominent band in the position of transferrin C, accompanied by four faint slower moving bands which coincided with the four transferrin components produced by the action of neuraminidase on transferrin C.

The transferrin pattern of cerebrospinal fluid in individuals homozygous for serum transferrin C showed two principal components, one of which appeared to contain no sialic acid. Haptoglobin, ceruloplasmin, and α2-macroglobulin were also present in cerebrospinal fluid.
PREVENTION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS (EAE) BY VITAMIN C DEPRIVATION
Authors: Mueller Peter S. , Kies Marian W. , Alvord Ellsworth C. , Shaw Cheng-Mei
Published: June 2004

Scorbutic guinea pigs injected with CNS and mycobacterium to induce experimental allergic encephalomyelitis (EAE) showed no clear-cut neurological signs and failed to show histological evidence of central nervous system damage. The degree of protection afforded by vitamin C deprivation was related directly to the duration of the scorbutogenic diet and inversely to the strength of the CNS challenge.

Vitamin C deprivation also abolished tuberculin sensitivity as measured by the PPD skin reaction. Upon restoration of vitamin C, the animals recovered their sensitivity to PPD but did not develop EAE.

It was further demonstrated that these effects of vitamin C deprivation were not related to inanition or to the endogenous levels of 17-hydroxycorticosteroids.
ALTERATION IN THE COLLAGEN CONTENT OF THE HUMAN UTERUS DURING PREGNANCY AND POST PARTUM INVOLUTION
Authors: Morrione Thomas G. , Seifter Sam
Published: June 2004

Quantitative collagen determinations demonstrate an increase of approximately 800 per cent in the collagen content of the human uterus at term as compared with the non-pregnant state. Following parturition, there is a rapid resorption of collagen. The amount of collagen which disappears from the post partum uterus is approximately 53 gm.

By the 8th day post partum, the human uterus has lost approximately 72 per cent of the total collagen which was present at term. The slopes of curves depicting alterations in collagen content of the uterus of the rat and human are virtually identical, despite the marked differences in the length of the gestational periods of the two species.

The alterations in the collagen content of the human uterus during pregnancy and involution closely follow changes in total uterine weight. There is a slight decrease in per cent collagen content of the uterus during pregnancy, and an increase in the water content of the post partum uterus.

Approximately 97 per cent of the collagen which is present in the human uterus at term is of the so called "insoluble" type. The physiological resorbability of uterine collagen, as evidenced by its post partum dissolution, cannot therefore be correlated with its in vitro solubility characteristics.

No collagenase was demonstrable in the myometrium of post partum uteri. A 2 day post partum uterus was found to contain an enzyme which slowly degraded gelatin at pH 3.85 but was virtually inactive at pH 7,0.

There is an increase in myometrial prolidase activity of approximately 75 per cent, commencing 2 days post partum. Prolidase activity remains elevated until the 8th day post partum, and subsequently falls to almost normal levels by the 5th post partum week.

During the process of involution, the post partum uterus shows histological evidence of edema and partial destruction of its reticular framework.
STUDIES ON THE RELATIONSHIP OF 5-HYDROXYTRYPTAMINE AND THE ENTEROCHROMAFFIN CELL TO ANAPHYLACTIC SHOCK IN MICE
Authors: Gershon Michael D. , Ross Leonard L.
Published: June 2004

Protection against anaphylactic shock in mice by reserpine has been shown to be a delayed phenomenon, probably not dependent upon a direct effect of reserpine. The release and depletion of catechol amines by reserpine show little likelihood of being responsible for protection because these substances are in themselves protective against anaphylactic shock, while ß-TM 10, a drug which interferes with their release is not. Since L-α-methyl dopa and reserpine both deplete serotonin, and since both protect against anaphylactic shock, it is proposed that serotonin depletion is responsible for the protection.

Enterochromaffin substance is depleted in anaphylactic shock. It is also depleted by reserpine and serotonin, both of which protect against anaphylactic shock when given prior to challenge with antigen. The amount of enterochromaffin substance seems to correlate with susceptibility to anaphylactic shock.

The behavior of animals undergoing anaphylactic shock and the effect of shock on body temperature is similar to the effects on behavior and temperature of treatment with reserpine, which is known to release serotonin. The effect of monoamine oxidase inhibition on animals undergoing anaphylactic shock is also similar to the effect of monoamine oxidase inhibition on animals given reserpine.

These results are consistent with the views that the release of serotonin is causally related to anaphylactic shock in mice and that serotonin is accumulated in the chromogenic material of the enterochromaffin cell.
INHIBITION OF CYTOCHROME OXIDASE BY AMINOACETONITRILE
Authors: Clemmons J. J. , Jackson E. B.
Published: June 2004

Aminoacetonitrile (AAN) decomposes with the formation of a substance that is a potent inhibitor of cytochrome oxidase. The inhibitor is probably cyanide. Connective tissue contains cytochrome oxidase that varies in amount with the maturity of the tissue and is also inhibited by the product of AAN decomposition.