bluuebunny/crossref_metadata_2025 huggingface dataset:
THE RENAL LESIONS OF ELECTROLYTE IMBALANCE
Authors: Oliver Jean , MacDowell Muriel , Welt L. G. , Holliday M. A. , Hollander W. , Winters R. W. , Williams T. F. , Segar W. E.
Published: June 2004

Renal tubular lesions during the early phases of progressive potassium depletion in rats were found in nephrons isolated by microdissection in two locations, the collecting tubules and the proximal convolutions. All other portions of the nephron, in particular the "distal tubule," i.e. ascending limbs of Henle's loop and distal convolutions, showed no structural alterations except the passive effects of dilatation and cellular compression which developed as a result of primary disturbances lower in the tubular system.

The alterations affected all the collecting tubules uniformly and took two forms; the more severe, a swelling and hyperplasia of the tubular epithelium and the lesser, an intracellular accumulation of granule droplets. The former was limited to the outer zone of the medulla, the latter to its inner zone. In the proximal convolution the structural alteration began in its middle third and extended downward towards the medulla; only occasional nephrons were affected.

The essential nature of the more severe epithelial lesion was similar in both collecting tubule and proximal convolution, beginning as a swelling of cell bodies, increasing to protoplasmic disturbances with disintegration of the mitochondrial pattern, followed by rupture of cells and nuclear disappearance. These retrogressive alterations were followed by prolific regenerative hyperplasia. In the collecting tubules of the outer zone these epithelial alterations were present in both the clear and the intercalcated cells; in the latter the swelling of the cells was not prominent, but the hyperplastic proliferative increase in their number was the predominating feature of the lesion when the dissected tubules were viewed intact in the continuity of their topographical relations.

The cellular alterations in the tubules are associated with an inability to concentrate the urine; reasons are given for considering this functional disturbance a correlate of the structural lesion in the collecting tubules.
A CYTOCHEMICAL STUDY OF THE L.E. BODIES OF SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Godman Gabriel C. , Deitch Arline D.
Published: June 2004

Microspectrophotometric comparison of lymphocyte nuclei and free L.E. bodies which are derived from them show a more than twofold average increase in the latter of protein basic groups revealed by naphthol yellow S binding, and tyrosine residues demonstrated by the Millon reaction. The alkaline fast green method for histones and the Sakaguchi reaction for arginine residues suggest that there is a marked loss and ultimate disappearance of histones in the course of formation of the L.E. body from a nucleus. It is postulated that the L.E. transformation entails influx of protein normally foreign to the nucleus, displacement of histone from combination of DNA, and association of the DNA with the new protein which is then responsible for masking the anionic groups of DNA.
GROWTH CHARACTERISTICS OF POLIOVIRUS IN HELA CELLS: NUCLEIC ACID METABOLISM
Authors: Maassab H. F. , Loh Philip C. , Ackermann W. Wilbur
Published: June 2004

The RNA and DNA contents of the nucleus and cytoplasm of the HeLa cell were determined. The rates of incorporation of P32 into the various nucleic acid fractions were established for the ordinary HeLa cell maintained under a set of standard conditions.

The changes in the rates of incorporation of P32 and in the amounts of RNA and DNA which occurred subsequent to infection with poliovirus were followed throughout the infectious cycle. These changes were correlated with the intracellular appearance of the newly formed virus. A net synthesis of RNA occurred in the cytoplasmic component of the cell. The increase was detectable 2 hours before the first appearance of demonstrable virus and reached a maximum (2.5 times normal) at 6 hours. Viral increase was not maximal before the 7th hour after infection.
AN ELECTRON MICROSCOPE STUDY OF THE GLOMERULUS IN NEPHROSIS, GLOMERULONEPHRITIS, AND LUPUS ERYTHEMATOSUS
Authors: Farquhar Marilyn G. , Vernier Robert L. , Good Robert A.
Published: June 2004

Renal biopsies from 16 patients with nephrosis, 7 patients with glomerulonephritis, and 3 patients with disseminated lupus erythematosus were studied with the electron microscope.

The observations presented indicate that early in the course of each of these diseases alterations occur in the fine structure of the glomeruli which serve to distinguish one disease process from another.

In nephrosis, some distortion of the organization of the epithelial foot processes was seen in all patients. These epithelial changes constituted the early, consistent lesion of the disease. There was frequently also a swelling of the endothelium.

In glomerulonephritis, pronounced proliferative changes involving the endothelium and to a lesser extent the epithelium, together with the laying down of a basement membrane-like material, represented the predominate pathologic processes. There was also a swelling of both endothelial and epithelial cytoplasm. The epithelial foot processes generally appeared normal.

In patients with a clinically "mixed" picture of nephrosis and nephritis, the glomerular changes were likewise "mixed," for various combinations of epithelial, endothelial, and basement membrane abnormalities were present.

In disseminated lupus erythematosus, a more or less generalized thickening of the basement membrane proper associated with a variable degree of endothelial proliferation was seen. It is suggested that an accentuation of the process of basement membrane thickening results in the "wire loop" appearance sometimes seen by light microscopy.

Although the earliest alterations in glomerular fine structure were characteristic for each of the disease processes, at later stages the changes were not always distinctive. The resulting scarred or "hyalinized" glomeruli, composed of relatively homogeneous, basement membrane-like material, and a few atrophic cells, appeared quite similar.

Although the functional implications of the structural changes observed remain obscure at this time, it is believed that insight into mechanisms may stem from such observations.
POLIOVIRUS PRECIPITINS
Authors: Le Bouvier George L.
Published: June 2004

Antigens present in poliovirus concentrates react with antibodies present in the serum of hyperimmunized monkeys to give type-specific precipitates. One or more bands of precipitate can be formed wherever such homotypic reactants, diffusing into an agar gel, meet in sufficient concentration and in equivalent proportions.

No qualitative differences have been detected between the type-specific reactions given by different strains of the same virus type; and no precipitates have been seen which could be called "group-specific." Non-specific precipitates have occasionally been observed.

Type-specific poliovirus precipitins are found in the serum of poliomyelitis patients. Their concentration has been measured by a standardized method. They tend to develop in parallel with neutralizing antibodies against the same virus type, increasing in amount during the first weeks of illness in those patients who show concurrent neutralizing antibody rises.

The precipitation reaction has proved valuable in the antigenic analysis of polioviruses. Its general adoption as a diagnostic procedure is perhaps unlikely; but it may be well worth applying for special purposes.
THE INFECTION OF CHIMPANZEES WITH ECHO VIRUSES
Authors: Itoh Heihachi , Melnick Joseph L.
Published: June 2004

The oral and parenteral infections of chimpanzees receiving echo Types 6 and 4 viruses successively are described. The two infections, spaced 2½ months apart, and given by the same route in each animal, failed to induce overt disease. The inapparent infections were demonstrated by virus excretion in the throat and the stools and the development of neutralizing antibodies. Complement-fixing antibodies also appeared after Type 6 infection, but fell more rapidly than the neutralizing antibodies.

After oral infection, echo-6 virus was found for equal periods in both the throat and feces, but echo-4 persisted in the throat for much longer periods than in the lower bowel. Almost no virus carriage occurred after parenteral inoculation. No true viremia was exhibited in any of the animals.

One of the chimpanzees had neutralizing antibodies against Type 6 virus in its pre-inoculation serum. It responded extraordinarily to the Type 6 exposure, developing antibody levels of 1:50,000 to echo-6, of 1:1024 against the echo-6' variant, and of 1:64 against the echo 6'' variant.

Although Type 4 antibodies developed after the exposure, they proved difficult to measure by ordinary methods. However, they could be satisfactorily assayed by the plaque reduction method.

Three other chimpanzees fed echo-2, echo-3, and an untypable echo virus, respectively, yielded results confirming those established with Types 4 and 6.
EFFECTS OF CELLULAR CONSTITUENTS OF MYCOBACTERIA ON THE RESISTANCE OF MICE TO HETEROLOGOUS INFECTIONS
Authors: Dubos René J. , Schaedler Russell W.
Published: June 2004

Vaccination with living attenuated tubercle bacilli (BCG) was found to increase the resistance of mice to infection with virulent staphylococci.

An even more striking protective effect could be elicited by intraperitoneal or subcutaneous injection of small amounts (0.1 mg. or more) of killed BCG cells.

The killed BCG cells retained most of their protective activity after prolonged heating at acid, neutral, or basic reactions—and after extraction with acetone, methanol, and NaOH (at pH 10.5). Some protective activity could be recovered in a fraction soluble in methanol at 55°C.

The protective effect against infection manifested itself in a prolongation of survival time following infection, and also in the fact that smaller numbers of staphylococci were recovered from the organs of infected mice. Both types of effects were still evident 10 weeks after vaccination.

Injection by the intraperitoneal route of killed cells of BCG, or of methanol extracts of them, elicited in mice a high level of protection against intravenous injection of Myco. fortuitum.

A protective effect quantitatively and qualitatively similar to that elicited by BCG, resulted from the intraperitoneal or subcutaneous injection of killed cells of Myco. fortuitum.
EFFECTS OF CELLULAR CONSTITUENTS OF MYCOBACTERIA ON THE RESISTANCE OF MICE TO HETEROLOGOUS INFECTIONS
Authors: Schaedler Russell W. , Dubos René J.
Published: June 2004

Injection of certain cellular constituents of mycobacteria into mice simultaneously with, or shortly after, infection with Staph. aureus or with Myco. fortuitum, markedly shortened the life of the infected animals. This infection-enhancing effect could be achieved by injecting the cellular constituents by either the intravenous, the intraperitoneal, or the subcutaneous route.

Suspensions of killed mycobacteria were injected into mice which had been infected several months before with small doses of various bacterial pathogens and which still harbored small numbers of living organisms in their organs. Under these conditions, a marked increase in the numbers of living bacteria in the organs of the treated mice could be detected within a very few days after treatment with the mycobacterial products, and a certain percentage of the animals died rapidly.

One of the first and most constant manifestations of the change in the infectious process from the chronic to the acute state was the appearance of a large microbial population in the liver. This happened even though Staph. aureus and Myco. fortuitum are rapidly cleared from the liver of normal mice.

In addition to killed cells of BCG and of Myco. fortuitum, pertussis vaccine and the purified lipopolysaccharide (endotoxin) of Gram-negative bacilli also proved capable of converting chronic bacterial infections into acute infectious processes.
STUDIES ON THE ETIOLOGY AND TRANSMISSION OF EPIDEMIC DIARRHEA OF INFANT MICE
Authors: Kraft Lisbeth M.
Published: June 2004

Transmission experiments have shown that epidemic diarrhea of infant mice of the CFW strain is infectious and communicable. Cage to cage spread can take place by the air-borne route. The agent appears to be a fairly heat-resistant virus that can be serially transferred and that is neutralized by specific hyperimmune antiserum from rabbits. Mice are susceptible to it by the oral route from at least the 3rd day after birth to the 10th or 11th day. Thereafter they appear to become resistant. The shortest incubation period observed has been 40 hours from the time of feeding infectious material; the longest period could not be ascertained under the conditions of test. Factors relative to the differentiation of this virus from other viruses are briefly discussed.
INTERRELATIONSHIPS BETWEEN EXPERIMENTAL HYPERCHOLESTEREMIA, MAGNESIUM REQUIREMENT, AND EXPERIMENTAL ATHEROSCLEROSIS
Authors: Vitale J. J. , White P. L. , Nakamura M. , Hegsted D. M. , Zamcheck N. , Hellerstein E. E. ,   With the Technical Assistance of P. Connors, A. Gotsis, and T. Faherty
Published: June 2004

The addition of cholesterol and cholic acid to a diet containing 24 mg. percent of magnesium, an amount normally required for young rats, resulted in magnesium deficiency in rats. This was characterized by hyperexcitability, hyperemia of the ears, calcium deposition in the kidney tubules, low serum magnesium levels, and decreased oxidative phosphorylation of heart mitochondria. All these lesions were prevented by raising the dietary magnesium level four to eight times.

Feeding the atherogenic diet produced the deposition of lipide in the aorta and in the heart valves. The extent of this intimal sudanophilia was reduced by large amounts of dietary magnesium although serum cholesterol values did not fall and usually rose. This represents perhaps the first clear cut disassociation between serum cholesterol values and the extent of intimal sudanophilia.

Raising the level of dietary protein from 10 to 20 per cent decreased the serum cholesterol levels and the extent of the kidney lesions. Thyroxine administration lowered the serum cholesterol values, abolished the kidney lesions and reduced the intimal sudanophilia. These effects occurred even though the serum magnesium levels remained low.
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.
ANTIGENICITY OF GELATIN
Authors: Maurer Paul H.
Published: June 2004

The effects of physical and enzymatic treatments of gelatin on the gelatin-antigelatin reaction have been presented. The data obtained indicate that the gelatin-antigelatin reaction is indeed a specific one. It appears that a definite limiting molecular size and specific molecular pattern of this molecular unit are necessary for reaction with antibody.
CHARACTERISTICS OF THE ADENOVIRUSES
Authors: Ginsberg Harold S.
Published: June 2004

The strains of types 1 to 4 adenoviruses studied attained maximum combination with host cells, strain HeLa, in 5 to 6 hours. During this adsorption period approximately 75 per cent of the total virus became associated with the host cells. Following adsorption of virus to HeLa cells, these agents underwent cyclic multiplication periods similar to bacterial and other animal viruses. The latent or eclipse period of the multiplication cycle for types 1 and 2 viruses was 17 hours, whereas the types 3 and 4 agents had a latent period 14 to 15 hours in length. The rate of viral propagation during the incremental period was very similar for types 1, 2, and 4 viruses, but was slower for the type 3 agent. During the incremental period of viral propagation newly synthesized virus was not released into the fluid phase of the culture and even after 6 days of viral multiplication when marked cytopathic alterations of the infected HeLa cells had occurred, the spontaneous release was only 2 to 6 per cent of the total virus detectable.
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.
TISSUE CULTURE STUDIES ON BACTERIAL ALLERGY IN EXPERIMENTAL BRUCELLOSIS
Authors: Heilman Dorothy H. , Howard Dexter H. , Carpenter Charles M.
Published: June 2004

Tissue culture methods have been used to investigate infectious allergy in experimental brucellosis. A study was made of the effect of whole cell Brucella antigen on cultures of spleen from normal and Brucella-infected guinea pigs. The degree of toxicity was based upon the inhibition of migration of wandering cells and upon the morphologic appearance of stained sections of tissue cultures at different periods of incubation. A suspension of heat-killed Br. suis was more toxic for splenic cells from guinea pigs infected with Br. suis than for normal splenic cells. Macrophages were more sensitive than leucocytes to the toxic action of the antigen. The degenerative changes observed in Brucella-sensitive cells exposed to the antigen were similar to the degeneration previously observed in cultures of tuberculin-sensitive cells in the presence of tuberculin. The specific toxicity of the whole Brucella antigen, however, was more marked than that of tuberculin. Preliminary experiments indicate that serum and plasma containing specific antibodies obtained from Brucella-infected guinea pigs reduce the toxic effect of the antigen in cultures of both normal and Brucella-sensitive cells. The protective action of the homologous antiserum was greater for Brucella-sensitive cells than for normal cells.
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

A steric and kinetic model for the sequence and mechanism of reactions leading to formation of a complex from an antibody, a haptene (quinidine), and a cell membrane (platelets), and to fixation of complement by the complex was deduced from the effects of varying the initial concentration of each component of the complex on the amount of complement fixed, from kinetic aspects of the sequential reactions, and from other chemical and physical properties of the various components involved. Theoretical results calculated using equations based on the model, which were derived by Dr. Terrell L. Hill, were similar in all respects to experimental results. Results of this study were consistent with the possibilities that the protein moiety of a haptenic antigen involved in development of an antibody which attaches to a cell is not necessarily a component of the cell, and that the cell reacts with the antibody by virtue of having a surface favorable for non-specific adsorption of certain haptene-antibody complexes.
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.
ELECTROPHORETIC STUDIES OF THE EXTRACELLULAR PRODUCTS OF GROUP A STREPTOCOCCI
Authors: Wannamaker Lewis W.
Published: June 2004

Concentrates of the extracellular products of group A streptococci were prepared which were essentially free of constituents of the medium. The extracellular products appeared to consist primarily of protein material. The yield of total extracellular products was of the order of magnitude of 10 mg. per liter of supernatant broth. When studied by zone electrophoresis, the concentrates showed protein over a wide distribution with distinct peaks in certain areas. The locations of streptolysin O, streptokinase, desoxyribonuclease, and ribonuclease activities were identified, and partial separation of these enzymes was achieved. Considerable variation in the electrophoretic patterns of the extracellular products from different strains was noted.
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.
STUDIES ON THE TRANSFER OF LYMPH NODE CELLS
Authors: Harris T. N. , Harris Susanna , Farber Miriam B.
Published: June 2004

The transfer to rabbits of homologous lymph node cells which have been incubated in vitro with Shigella-trypsin filtrate leads to the appearance of agglutinins to Shigella in the sera of the recipients. In the present study it has been found that the prior injection of the prospective recipients with blood leucocytes from the donor animals prevented the appearance of anti-Shigella agglutinins. The following observations have been made in this system:

1. The degree of the pre-injection effect was found to be a function of the number of leucocytes injected and of the interval between such pre-injection and the transfer of the antigen-incubated lymph node cells.

2. The pre-injection of leucocytes at appropriate intervals could also cause the failure of antibody to appear in sera of recipients of lymph node cells when these were obtained from donor rabbits injected with Shigella, 1, 2, or 3 days prior to cell transfer.

3. Agglutinins failed to appear in cell-transfer experiments after the pre-injection not only of blood leucocytes, but also of lymph node cells, peritoneal exudate cells, or thymus cells of rabbits. This effect was not brought about by pre-injection of erythrocytes of rabbits or leucocytes of chicken, cow, or horse. The pre-injection of leucocytes of human blood had an effect of partial suppression.

4. When the leucocytes for pre-injection were pooled from groups of rabbits, either the prospective donors of the lymph node cells or other rabbits, essentially complete suppression of agglutinin titers occurred regularly. When the leucocytes for pre-injection were obtained from an individual rabbit and the lymph node cells from another rabbit the suppression of the recipients' titers occurred sporadically.

5. When the recipient's own leucocytes were pre-injected the subsequent agglutinin titers were somewhat lower than those of the non-pre-injected controls. When the recipient's whole blood was re-injected as the source of leucocytes the subsequent agglutinin titers were as high as those of the non-pre-injected controls.

6. The pre-injection effect was not obtained if the leucocytes had been heated, frozen and thawed, suspended in distilled water, lyophilized, or treated with sodium iodoacetate. However, sonic oscillation or x-irradiation of the leucocytes had no effect on their capacity to bring about the pre-injection effect.
DETECTION OF "NON-PRECIPITATING" ANTIBODIES IN SERA OF INDIVIDUALS ALLERGIC TO RAGWEED POLLEN BY AN IN VITRO METHOD
Authors: Gordon J. , Rose B. , Sehon A. H.
Published: June 2004

A hemagglutination test capable of demonstrating antibodies in sera of ragweed-sensitive individuals has been described in detail. This test involves coupling of the antigen to rabbit erythrocytes via stable azo bonds. The antigen-coated cells are then suspended in the serum which is suspected to contain the homologous antibodies. The test has been shown to be specific and highly sensitive. Precipitating antibodies to ragweed pollen extract produced in experimental animals can be demonstrated in dilutions as high as 105 to 107, while antibodies to ragweed in allergic sera are detected only in dilutions of the order of 103. Positive results were obtained with all sera from treated or non-treated allergic individuals containing skin-sensitizing and/or blocking antibodies. Absorption of these sera with antigen-coated erythrocytes yielded a supernatant devoid of either skin-sensitizing, blocking, or hemagglutinating capacity. It is concluded that the hemagglutinating factor has the properties of a divalent antibody.
GENETICS OF SOMATIC MAMMALIAN CELLS
Authors: Tjio J. H. , Puck Theodore T.
Published: June 2004

A convenient, reliable method for chromosome delineation of animal cells grown as monolayers on glass has been applied to human, opossum, and Chinese hamster cells.

Tissue cultured cells from 5 different, normal organs of 7 different human subjects uniformly displayed the expected chromosome number of 46 and showed no variations in morphology or number other than the expected sex differences and a small incidence of polyploidy.

The chromosomes of normal cells from the American opossum were as uniform as those of human cells. Cells of the inbred Chinese hamster demonstrated appreciable karyotype variability, the cause of which is under investigation.

The chromosome number and morphology of cells from normal human tissues have remained constant after more than 5 months of continuous, rapid growth in tissue culture involving scores of vessel transfers and a number of generations equivalent to many billions of progeny.

By the use of routine recloning, even cells of malignant, aneuploid constitution have been maintained in active growth for 3 years and hundreds of generations, with stable chromosomal and metabolic characteristics.

The cells of the American opossum and Chinese hamster which possess only 22 chromosomes have been established in vitro and are especially suitable for genetic studies. The readily recognizeable Y and X chromosomes of the male opossum are particularly favorable as cytological markers.

Photomicrographs of the chromosomes of the various cells employed are presented.
STUDIES ON EXPERIMENTAL SHIGELLOSIS
Authors: McGuire C. David , Floyd Thomas M.
Published: June 2004

Experimental Shigella flexneri 3 infections produced in normal mice have been described. The passage of viable Shigella through the stomach of orally infected animals, and the persistence of the organisms in the intestine for periods of 5 to 7 days, with an increase in bacterial numbers, indicated that true infection was produced. Blood culture studies showed that a Shigella bacteriemia occurred after either oral or parenteral administration of Shigella to normal mice. Mice infected orally revealed mild, but consistent pathological changes, including mesenteric hemorrhage, liver and spleen hypertrophy, and occasional diarrhea.
STUDIES ON EXPERIMENTAL SHIGELLOSIS
Authors: McGuire C. David , Floyd Thomas M.
Published: June 2004

Host resistance to Shigella infections can be decreased by non-specific physical stress. Fasting lowers the number of Shigella required for a parenteral LD50 dose. While the LD50 by the oral route is larger in fasted than in nonfasted animals, the fasted host's susceptibility to oral infection is increased as evidenced by the increased fecal Shigella carrier state, duration of intestinal infection, and increased incidence of Shigella bacteriemia.

Fatigue also increases the animal's susceptibility to shigellosis, but to a lesser extent than does fasting.