bluuebunny/crossref_metadata_2025_split huggingface dataset:
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Petersdorf Robert G. , Keene Willis R. , Bennett Ivan L. 
Published: June 2004

The "endogenous serum pyrogen" that appears in the circulating blood after a single intravenous injection of endotoxin does not produce leukopenia in normal animals, fails to provoke the local Shwartzman reaction, and elicits no "tolerance" when injected daily. Suppression of the febrile response to endotoxin by prednisone does not prevent the appearance of pyrogen in the blood.
Animals given large amounts of endotoxin daily continue to respond with high fevers despite failure of endogenous serum pyrogen to appear in detectable amounts after the first two or three injections. Analysis of the response to daily injections shows clearly that the fever during the first 2 hours after administration of endotoxin is unrelated to levels of endogenous serum pyrogen; in contrast, the magnitude of the fever after the 2nd hour correlates well with endogenous pyrogen in some instances. The leukopenic response to endotoxin could not be correlated with the appearance of endogenous serum pyrogen.
The differences between endotoxin and endogenous pyrogen and the similarities between leukocyte extracts (sterile exudates) and endogenous pyrogen are summarized and discussed. Dissociation of the febrile response to bacterial endotoxin and levels of endogenous serum pyrogen are discussed and it is concluded that a mechanism involving both direct and indirect action of endotoxins offers the best explanation for the pyrogenic action of these bacterial products.
THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION
Authors: Kilbourne Edwin D. ,   With the Technical Assistance of Barbara Ann Pokorny
Published: June 2004

Cortisone is a highly potent inhibitor of influenza virus synthesis in the chick embryo, inducing manifest inhibition in doses of 0.1 to 1.0 µg/egg.
Inhibition of viral synthesis is only temporarily manifest. As infection continues, the negation by cortisone of the self-limiting effects of viral autointerference obscures the coincident cortisone effect on synthesis.
The inhibitory effect of cortisone may be induced late in the course of viral multiplication, after conclusion of the latent period.
It is proposed that inhibition of viral synthesis with cortisone is a corollary of the steroid's inhibitory effects on growth and protein synthesis of the infected host.
The role of adrenal corticoids in the regulation of infection with obligate intracellular parasites deserves continued investigation.
STUDIES ON THE EFFECT OF TRITON (WR-1339) ON GUINEA PIG TISSUES
Authors: Patnode Robert A. , Hudgins Paul C. , Janicki Bernard W. 
Published: June 2004

Guinea pigs given three subcutaneous injections of triton WR-1339, 300 mg./kg., at 3 day intervals develop an intense lipemia as evidenced by marked increases in serum phospholipide, free cholesterol, ester cholesterol, neutral fat, and total fatty acids. The total fatty acid content of the lung, liver, and spleen, however, remains unchanged. No qualitative change in the fatty acids of the lung and liver from treated animals could be detected by the methods used. The injection of triton was found to diminish slightly the cholesterol content of the adrenal glands.
The implications of these findings are discussed in relation to an understanding of the mechanism involved in the therapeutic action of triton in experimental tuberculosis.
THE IN VITRO ACTION OF HYDROCORTISONE ON LEUCOCYTE MIGRATION
Authors: Ketchel Melvin M. , Favour Cutting B. , Sturgis Somers H. ,   With the Technical Assistance of Aurelia C. Koros and Frances Mao
Published: June 2004

Hydrocortisone inhibits the ameboid migration of human leucocytes when added in vitro. The dose-response curve for the reaction between this steroid and leucocytes can be best expressed by a logarithmic plot of the steroid concentrations.
Tetrahydrocortisone and desoxycorticosterone had no effect on in vitro leucotyte migration.
STUDIES ON THE GENERALIZED SHWARTZMAN REACTION
Authors: Pappas George D. , Ross Michael H. , Thomas Lewis 
Published: June 2004

The intravascular fibrinoid which is deposited in glomerular capillaries of the rabbit during the generalized Shwartzman reaction has been studied with the aid of the electron microscope. In one group of animals the reaction was produced by two intravenous injections of Escherichia coli lipopolysaccharide endotoxin, spaced 24 hours apart. In another, a single dose of endotoxin was followed, 1 hour later, by intravenous liquoid (sodium polyanethol sulfonate).
The appearance of fibrinoid was the same in the two groups. Initially, fibrinoid deposition occurred on the irregular, swollen surfaces of the endothelial cells within the capillary lumen. Subsequently, the fibrinoid mass increased to such proportions that the capillary lumen was completely occluded.
Fibrinoid was found to be composed of unbranched fibrils, having a diameter of 200–300 angstroms and an axial repeating structure of 120 A.
The basement membrane (lamina densa) underwent no change in appearance during the time when fibrinoid was being laid down.
Balloon-like vesicles were consistently encountered in endothelial cells of glomerular capillaries after two doses of endotoxin, and also in animals given one injection of endotoxin followed by liquoid.
The possible significance of the observations are discussed. It is suggested that they are compatible with the hypothesis, proposed earlier, that intravascular fibrinoid, in the generalized Shwartzman reaction, is derived from fibrinogen.
ALTERATIONS IN THE BLOOD COAGULATION SYSTEM INDUCED BY BACTERIAL ENDOTOXIN
Authors: McKay Donald G. , Shapiro Sandor S. 
Published: June 2004

The intravenous injection of bacterial endotoxins alter the coagulation system of rabbits' blood in vivo. Twenty-four hours after the first injection the fibrinogen level rises to twice normal values. The second injection at this time causes a 30 to 40 per cent decrease in fibrinogen content in 4 hours. Twenty hours later it again rises to twice normal values. A marked decrease in whole blood coagulation times in silicone occurs 4 hours after both injections but rises to normal values 24 hours following each injection. The circulating platelets drop from average levels of 300,000/c.mm. to 150,000/c.mm. after the first injection. The platelets remain at this low level and decrease to less than 100,000 after the second injection. During this time no fibrinolytic or fibrinogenolytic activity can be detected. Also, there is no significant change in the one stage prothrombin times or antithrombin titres.
The marked decrease in circulating fibrinogen at the time when intracapillary thrombi are formed suggests that the "hyaline" thrombi of the generalized Shwartzman reaction are composed, in part, of fibrin.
There appears to be a relationship between the level of circulating fibrinogen at the time of injection of bacterial endotoxin and the extent of the thrombosis. The higher the preinjection fibrinogen level, the more extensive is the thrombosis. There is also a relationship between the amount of fibrinogen loss and the extent of thrombosis after the injection. The more extensive the thrombosis the greater is the postinjection decrease in circulating fibrinogen.
A comparison between the response of the hemostatic mechanism to tissue thromboplastin and bacterial endotoxin indicates that the latter acts in a unique manner and not by way of a simple "thromboplastic" activity.
From the hematological standpoint, "preparation" for the generalized Shwartzman reaction is accompanied by an increased circulating fibrinogen, leukocytosis, and thrombocytopenia.
STUDIES ON THE PATHOGENESIS OF FEVER WITH INFLUENZAL VIRUSES
Authors: Atkins Elisha , Huang Wei Cheng 
Published: June 2004

A substance with pyrogenic properties appears in the blood streams of rabbits made febrile by the intravenous inoculation of the PR8 strain of influenza A and Newcastle disease viruses (NDV). By means of a technique involving passive transfer of sera from animals given virus to recipient rabbits, the titer of circulating pyrogen was found to be closely correlated with the course of fever produced by virus.
Certain properties of the pyrogen are described which differentiate it from the originally injected virus and suggest that the induced pyrogen is of endogenous origin. These properties resemble those of endogenous pyrogens occurring in other forms of experimental fever.
The source of virus-induced pyrogen is unknown. In vitro incubation of virus with various constituents of the circulation did not result in the appearance of endogenous pyrogen.
Granulocytopenia induced by HN2 failed to influence either fever or the production of endogenous pyrogen in rabbits injected with NDV. Similarly, the intraperitoneal inoculation of NDV into prepared exudates did not modify the febrile response. These findings do not lend support to the possibility that the polymorphonuclear leukocyte is a significant source of endogenous pyrogen in virus-induced fever.
It is concluded that the liberation of an endogenous pyrogen from some as yet undefined source is an essential step in the pathogenesis of fever caused by the influenza group of viruses.
STUDIES ON THE ACTIVATION OF A PROESTERASE ASSOCIATED WITH PARTIALLY PURIFIED FIRST COMPONENT OF HUMAN COMPLEMENT
Authors: Lepow Irwin H. , Ratnoff Oscar D. , Levy Lawrence R. 
Published: June 2004

It has been found that under a wide range of physico-chemical conditions a positive correlation exists between the rate of disappearance of hemolytically active, partially purified first component of human complement and the rate of activation of an esterase hydrolyzing N-acetyl-L-tyrosine ethyl ester. Both reactions follow the kinetic equation for second order autocatalysis, with an apparent energy of activation of 31,000 calories per mol. They occur optimally at pH 7.3–7.7 and are inhibited by ionic strengths greater than 0.15, by 5 x 105 M ethylenediaminetetraacetic acid, and by a heat-labile serum inhibitor which appears unrelated to any component of complement. The activation of first component to esterase resembles closely the activation of trypsinogen to trypsin. Partially purified first component, containing plasminogen, may also be activated to esterase by addition of streptokinase.
The significance of these data with respect to the postulated existence of first component as a proesterase and its possible role in complement-"fixation" is discussed.
A BIOCHEMICAL AND MORPHOLOGIC STUDY OF MYELINATION AND DEMYELINATION
Authors: Majno Guido , Karnovsky Manfred L. 
Published: June 2004

Samples of normal grey matter, white matter, and peripheral nerves obtained from rats were incubated in Warburg vessels with glucose and a labelled lipide precursor (acetate, phosphate, choline, glycerol, glucose). The total lipides were then extracted and their radioactivity measured.
The preparations were compared with respect to dry weight, lipide content, O2 uptake, and ability to incorporate the various substrates into the lipides. Grey matter was found to be the least damaged by incubation, white matter the most. Damage to the tissue depressed lipogenesis to a greater extent than respiration.
Five substrates were compared with respect to their degree of incorporation into the lipides of the various preparations. White matter, which had a greater oxygen uptake than peripheral nerves, showed the lowest degree of incorporation for most of the substrates studied. The results suggest that there are considerable quantitative differences in the metabolism of central and peripheral myelin.
In the sciatic preparations, oxygen uptake and lipogenesis from acetate were found to decrease from the proximal to the distal end of the nerve. This finding may be relevant to the pathogenesis of peripheral neuropathies.
The growth and metabolic activity of peripheral nerves were studied in rats aged 1 to 500 days, and the biochemical and histological findings were correlated. The results indicated that the lipogenetic activity of the Schwann cell was lowest in the newborn animal, and reached its peak at about 20 days. Comparative data were also obtained from the cerebral cortex.
The growth pattern of peripheral nerves was distinctly different from that of the brain. With respect to changes in tissue weight, respiration, and lipogenesis, growing peripheral nerve correlated with body weight, while the brain matured much more rapidly.
COLOMINIC ACID, A POLYMER OF N-ACETYLNEURAMINIC ACID
Authors: Barry Guy T. 
Published: June 2004

All acidic carbohydrate has been isolated from the culture medium of the enteric microorganism E. coli K235 L+O. This substance has been named colominic acid.
N-acetylneuraminic acid, which has been isolated from the hydrolysate of colominic acid, is believed to be the monomer unit from which colominic acid is constituted.
Colominic acid is not antigenic in rabbits. Tests have failed to reveal a relationship between the ability of E. coli K235 to elaborate colominic acid and its virulence in mice.
BLOOD PRESSURE, CHOLESTEROL CONTENT OF SERUM AND TISSUES, AND ATHEROGENESIS IN THE RAT
Authors: Deming Q. B. , Mosbach E. H. , Bevans M. , Daly M. M. , Abell L. L. , Martin E. , Brun L. M. , Halpern E. , Kaplan R. 
Published: June 2004

Rats on a stock diet with added cholesterol, cholic acid, and thiouracil developed increased concentrations of cholesterol, total lipide, and beta lipoprotein in the serum, and an increased content of cholesterol in the liver and carcass, despite the fact that the diet produced a cessation of endogenous cholesterol synthesis. Rats with high serum lipide concentrations developed intimal lesions similar to those of human atherosclerosis.
The induction of hypertension by desoxycorticosterone and salt accelerated the development of hypercholesterolemia, hyperlipemia, increase in tissue cholesterol content, and atherosclerotic changes in the intima. Hypertension induced by renal artery constriction also intensified the hypercholesterolemia and hyperlipemia. On the other hand, rats receiving desoxycorticosterone acetate without salt or salt without desoxycorticosterone acetate did not show any intensification of hypercholesterolemia or hyperlipemia.
The extent of the atherosclerotic lesions was correlated with the concentration of cholesterol in the serum. There was also a positive correlation between blood pressure and the degree of hypercholesterolemia. It remained uncertain whether the increase in atherosclerosis in the hypertensive animals was dependent on the increased lipide content of serum and tissues or on a local effect of the elevated blood pressure.
CYTOLOGICAL ABERRATIONS IN CULTURES OF "NORMAL" MONKEY KIDNEY EPITHELIAL CELLS
Authors: Kleinfeld Ruth , Melnick Joseph L. 
Published: June 2004

A cytological study was made of short term primary cultures of monkey kidney epithelial cells grown in serum-containing (M-H) and synthetic (SM-2) media. The mitotic activity of the cultures reached a peak 3 to 5 days after seeding, and rapidly declined if the medium was not changed. With replenishment at 48 hour intervals a high mitotic rate was maintained through the 8th day. Cultures subjected to a glycine- and glucose-deficient medium showed a sharp decline in mitotic activity within 24 hours. When such cultures were replenished a burst of mitotic activity occurred 20 to 30 hours later.
Mitotic aberrations such as multipolar spindles, anomalous spindles with scattered chromosomes, lagging or precocious movement of chromosomes, chromosome fragments, and chromosome bridges were found in all cultures ranging from 16 to 40 per cent of the dividing cells. Non-mitotic aberrations such as giant nuclei, multinucleate cells, nuclear fragmentation, micronuclei, nuclear inclusions, and phagocytosis were found in approximately 3 to 7 per cent of the non-dividing cell population. The frequency and types of mitotic abnormalities were generally independent of the medium used and the mitotic index of the cultures.
IMMUNOREACTIONS INVOLVING PLATELETS
Authors: Shulman N. Raphael 
Published: June 2004

Quantitative aspects of platelet agglutination and inhibition of clot retraction by the antibody of quinidine purpura were described. The reactions appeared to depend on formation of types of antibody-quinidine-platelet complexes which could fix complement but complement was not necessary for these reactions. Complement fixation was at least 10 times more sensitive than platelet agglutination or inhibition of clot retraction for measurement and detection of antibody activity.
Although it has been considered that antibodies of drug purpura act as platelet lysins in the presence of complement and that direct lysis of platelets accounts for development of thrombocytopenia in drug purpura, the present study suggests that attachment of antibody produces a change in platelets which is manifested in vitro only by increased susceptibility to non-specific factors which can alter the stability of platelets in the absence of antibody. The attachment of antibody to platelets in vivo may only indirectly affect platelet survival.
In contrast to human platelets, dog, rabbit, and guinea pig platelets, and normal or trypsin-treated human red cells did not agglutinate, fix complement, or adsorb antibody; and intact human endothelial cells did not fix complement or adsorb antibody.
Rhesus monkey platelets were not agglutinated by the antibody but did adsorb antibody and fix complement although their activity in these reactions differed quantitatively from that of human platelets.
Cinchonine could be substituted for quinidine in agglutination and inhibition of clot retraction reactions but quinine and cinchonidine could not.
Attempts to cause passive anaphylaxis in guinea pigs with the antibody of quinidine purpura were not successful.
IMMUNOREACTIONS INVOLVING PLATELETS
Authors: Shulman N. Raphael 
Published: June 2004

Regulated intravenous doses of quinidine were given to patients with the antibody of quinidine purpura to produce controlled thrombocytopenia without clinical sequelae. The degree of thrombocytopenia and the rate at which it developed were dependent on the relative plasma concentration of quinidine and antibody. By relating in vivo changes in platelet levels to concurrent in vitro tests for antibody activity and to quantitative relationships between reactants determined in Papers I and III of this series, it was concluded that the amount of antibody which attaches to platelets when thrombocytopenia develops is insufficient to cause complement fixation or platelet agglutination. Platelets do not appear to be destroyed directly by reaction with antibody in vivo. The minimal amount of antibody which does attach to platelets in vivo appears to increase their susceptibility to the usual mechanisms of sequestration.
Megakaryocytes and blood vessels do not appear to be affected directly by the antibody which causes quinidine purpura, and hemorrhagic manifestations of the disease appear to be consequent to changes in platelets alone.
A safe method of performing in vivo tests for the presence of an antibody of drug purpura is described.
The implications of the present work in idiopathic thrombocytopenic purpura are discussed.
CELLULAR MECHANISMS OF PROTEIN METABOLISM IN THE NEPHRON
Authors: Oliver Jean , MacDowell Muriel 
Published: June 2004

1. The exaggeration of "hyaline droplet" formation observed in the renal lesion of epidemic hemorrhagic fever when treated with the infusion of large amounts of human serum albumin and the histochemical characteristics of the droplets so formed afford evidence towards their identification with the protein absorption droplets of experimental procedures and with those that occur in other renal diseases.
2. Protein absorption droplets (hyaline droplets) are the visible aspect of pathological modifications of a physiological process; i.e., the continuing reabsorption of plasma proteins by the proximal convolutions.
3. The mitochondria of the renal cells are directly involved in both the physiological and the abnormal reabsorption and disposal of the plasma proteins; the absorption droplets are a complex of reabsorbed proteins and mitochondrial substances and enzymes; they result whenever disposal is at a rate insufficient to prevent accumulation.
4. Failure of intracellular disposal of reabsorbed protein is determined by (a) the quantitative and qualitative characteristics of the protein and (b) by the functional state of renal cell.
5. Various factors in renal disease that result in disturbances of reabsorption and of intracellular disposal, both with and without droplet formation, are described.
THE SWINE LUNGWORM AS A RESERVOIR AND INTERMEDIATE HOST FOR HOG CHOLERA VIRUS
Authors: Shope Richard E. 
Published: June 2004

Suspensions of adult lungworms, procured from swine that were outwardly healthy but derived from eggs passed by swine with hog cholera, induced this disease in a small proportion of swine into which they were injected intramuscularly. This result was achieved in both lungworm-free and lungworm-infested swine, though perhaps slightly more regularly in the lungworm-infested animals. Swine that had had an intramuscular injection of lungworm suspension and that had remained normal, developed hog cholera much more regularly following the ingestion of lungworm larvae of cholera origin than did swine not previously injected with lungworms. The findings described were markedly dependent upon season and were regularly reproducible only during the first 4 or 5 months of the year.
The results presented are considered as further evidence that the swine lungworm serves as reservoir and intermediate host for hog cholera virus and that the virus is ordinarily carried by the lungworm in a masked form which must be provoked to pathogenicity by some stress before it can cause obvious disease in swine.