bluuebunny/crossref_metadata_2025 huggingface dataset:
Invariant chain is the core protein of the Ia-associated chondroitin sulfate proteoglycan.
Authors: Sant A J , Cullen S E , Giacoletto K S , Schwartz B D
Published: June 2004

The murine Ia-associated chondroitin sulfate proteoglycan (CSPG) was studied both biochemically and immunochemically to determine the nature of its core protein. Chondroitinase ABC or chondroitinase AC treatment of the CSPG digested the chondroitin sulfate glycosaminoglycan, yielding a core protein that migrated with an apparent molecular weight of 38,000. Comparative V8 protease digestion of the CSPG core protein and conventional invariant glycoproteins yielded homologous peptides, indicating that the core protein and invariant chain were structurally similar. The purified CSPG and its core protein were both shown to react directly with the monoclonal anti-invariant chain antibody, In-1. Comparative tryptic peptide analysis by high performance liquid chromatography demonstrated coelution of the majority of the peptides from the invariant chain and the CSPG core protein. Collectively, these results indicate that the CSPG is an alternatively processed form of invariant chain.
Immune regulation of in vitro murine megakaryocyte development. Role of T lymphocytes and Ia antigen expression.
Authors: Long M W , Shapiro D N
Published: June 2004

Mitogen-activated murine T lymphocytes or T cell hybridomas produce an activity (megakaryocyte [Mk] potentiator activity) that enhances the in vitro growth and development of Mk colonies. This activity was found in optimal concentrations (2.5%) in T cell hybridoma-conditioned medium, and was also produced by feeder layers of concanavalin A-activated T cells. A subpopulation of murine Mk progenitor cells (colony-forming units; CFU-Mk) bears the Ia antigen. Separate experiments indicated that T cell products stimulate CFU-Mk by increasing their basal levels of Ia expression as well as the frequency of cells actively synthesizing DNA. The hypothesis that the expression of this antigen was related to the cell cycle status of these progenitor cells was confirmed in studies that indicated that ablation of actively cycling cells in vivo abrogated the cytotoxic effects of anti-Ia monoclonal antibodies. The interdependence of T cell lymphokine regulation of both Ia expression and cell cycle status was also seen in in vitro experiments in which Ia+ progenitor cells were eliminated by complement-dependent cytotoxicity. The removal of Ia+ cells prevented 5-hydroxyurea-mediated inhibition of cells in S phase. We hypothesize that immune modulation of megakaryocytopoiesis occurs via soluble T cell products that augment Mk differentiation. Further, the mechanism of immune recognition/modulation may occur via Ia antigens present on the surface of these progenitor cells.
Properties of purified T cell subsets. I. In vitro responses to class I vs. class II H-2 alloantigens.
Authors: Sprent J , Schaefer M
Published: June 2004

In light of the widely accepted view that Ia-restricted L3T4+ T helper cells play a decisive role in controlling the differentiation of Lyt-2+ cells, experiments were designed to examine whether Lyt-2+ cells can respond to antigen in the absence of L3T4+ cells. The results showed that highly purified Lyt-2+ cells gave high primary mixed lymphocyte reactions (MLR) to various class I differences, including both mutant and allelic differences; responses to class II (Ia) differences were generally undetectable with Lyt-2+ cells. The intensity of MLR to class I differences was not affected by addition of anti-L3T4 monoclonal antibodies (mAb) to the cultures or by removing T cells from the stimulator populations. Negative selection experiments showed that Lyt-2+ cells could respond to class I differences across Ia barriers. MLR of purified Lyt-2+ cells peaked on days 3-4 and then fell sharply; background responses with syngeneic stimulators (auto-MLR) were virtually absent. Parallel experiments with purified L3T4+ cells showed that this subset responded in MLR only to class II (Ia) and not class I differences, reached peak responses only on day 6 rather than days 3-4, and often gave high auto-MLR. Within the first 3-4 d of culture, MLR were generally higher with Lyt-2+ cells than L3T4+ cells. Although no evidence could be found that Ia-restricted L3T4+ cells were required for the response of Lyt-2+ cells, presentation of antigen by Ia+ cells appeared to be essential. Thus, responses were ablated by pretreating stimulator cells with anti-Ia mAb plus C'. Significantly the failure of Lyt-2+ cells to respond to anti-Ia plus C'-treated stimulators could not be restored by adding syngeneic spleen cells; addition of IL-2 led to only a minor (15%) restoration of the response. It is suggested that Ia+ cells provide an obligatory second signal required by Lyt-2+ cells.
A fast-acting elastase inhibitor in human monocytes.
Authors: Remold-O'Donnell E
Published: June 2004

A proteinase inhibitor active against neutrophil and pancreatic elastase was detected in extracts of cultured human monocytes and the human monocyte-like cell line U937. This component forms a covalent complex with the active site of elastase; the complex is stable in boiling sodium dodecyl sulfate solution, and is susceptible to nucleophilic cleavage. The activity of the elastase inhibitor is not detected in extracts of freshly isolated monocytes, but becomes detectable when the monocytes are allowed to mature in culture, with maximum levels occurring at 5-7 d. The monocyte inhibitor is fast-acting; its reaction with 125I-labeled elastase is complete in less than 1 min at 37 degrees C. Analysis by electrophoresis and studies using a heteroantiserum to alpha 1-proteinase inhibitor demonstrated that the elastase inhibitor of monocytes/U937 cells is not identical to alpha 1-proteinase inhibitor, the major elastase inhibitor of blood plasma. The extent of conversion of 125I-elastase to the 125I-elastase-inhibitor complex is proportional to the amount of U937 extract or cultured monocyte extract, indicating that this reaction can serve to quantify the elastase inhibitor. The elastase inhibitor is an abundant component in mature monocytes, with greater than or equal to 1.5 X 10(6) molecules/cell (greater than or equal to 12 micrograms per 10(8) cells, greater than 0.1% of total cell protein). Its mol wt is estimated at 50,000. Thus, the monocyte inhibitor should be classified as a putative regulator of neutrophil (and monocyte) elastase activity at inflammatory sites. This designation is based on the properties of the molecule, including its high concentration in maturing monocytes, its affinity for elastase, and its fast reaction with this enzyme.
T cell receptor beta chain gene rearrangements in lymphoproliferative disorders of large granular lymphocytes/natural killer cells.
Authors: Rambaldi A , Pelicci P G , Allavena P , Knowles D M , Rossini S , Bassan R , Barbui T , Dalla-Favera R , Mantovani A
Published: June 2004

Twelve cases of T gamma LPD (lymphoproliferative disorders of Fc gamma receptor-bearing T cells) involving an expansion of large granular lymphocyte/natural killer (LGL/NK) cells were investigated for the expression of LGL/NK-associated markers and for T beta gene rearrangement. All the cases selected were classified as T gamma LPD on the basis of morphology, function, and phenotype of the circulating cells. 10 to 12 cases displayed clonal rearrangements of the T beta locus and expression of the T3 antigen, whereas the 2 remaining cases displayed the germline configuration of the T beta gene and no expression of the T3 antigen. T8, Mol, B73.1, and N901 antigens were variably expressed among both T beta+T3+ and T beta-T3- T gamma LPD cases. We suggest that individual T gamma LPD cases represent the clonal expansion of cells frozen at different stages of differentiation/activation within an individual hematopoietic LGL/NK lineage.
Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts.
Authors: Dayer J M , Beutler B , Cerami A
Published: June 2004

Cachectin/TNF (tumor necrosis factor), an endotoxin-induced murine macrophage hormone implicated in the pathogenesis of cachexia and shock, has been found capable of stimulating collagenase and prostaglandin E2 (PGE2) production by isolated human synovial cells and dermal fibroblasts. This bioactivity associated with cachectin is comparable to that observed with the monokine interleukin 1 (IL-1), previously suggested as the major mediator of proteolysis. The ability of cachectin/TNF to stimulate collagenase and PGE2 production suggests that it may play a role in tissue destruction and remodelling, as these processes occur in inflammatory diseases.
INFECTIOUS FIBROMA OF RABBITS
Authors: Shope Richard E.
Published: June 2004

In the experiments presented, Virus myxomatosum was observed to produce only a localized fibromatous or myxomatous orchitis when injected into the testicles of cottontail rabbits. This type of disease was quite unlike the acute fatal illness which the virus caused in domestic rabbits. 10 serial passages of Virus myxomatosum through cottontail rabbits, covering a total elapsed time of 140 days, failed to alter its pathogenicity for domestic rabbits. Although it proved impossible to convert the myxoma virus into fibroma virus by serial passage in cottontail rabbits, it was found that these animals, recovered from myxoma, had a solid resistance to infection with the fibroma virus. Furthermore, their sera possessed neutralizing antibodies effective against the fibroma virus as well as Virus myxomatosum. A similar cross-immunological relationship was observed in the cases of domestic rabbits that had survived an attack of infectious myxoma.
SEROLOGICAL REACTIONS WITH A VIRUS CAUSING RABBIT PAPILLOMAS WHICH BECOME CANCEROUS
Authors: Kidd John G. , Beard J. W. , Rous Peyton
Published: June 2004

The serum of a rabbit with large cancers resulting from the transplantation of a squamous cell carcinoma that had arisen from a virusinduced papilloma, possessed the power to neutralize the virus, and so too in less degree did that of an animal of the same transplantation series in which a small nodule had developed. The sera of rabbits carrying tar papillomas or the Brown-Pearce carcinoma proved wholly devoid of effect on the virus. The implantation of Brown-Pearce tumor material mixed with virus did not lead to an enduring establishment of the latter in the resulting growths, nor to any immediate changes in their morphological character.

The significance of the facts is discussed.
STUDIES ON THE SOLUBLE PRECIPITABLE SUBSTANCES OF VACCINIA
Authors: Craigie James , Wishart F. O.
Published: June 2004

1. Thermolabile and thermostable soluble precipitable substances dissociate in vitro from the elementary bodies of vaccinia.

2. These substances are serologically related to the soluble precipitable substances found in suspensions of fresh vaccine pulp.
EXPERIMENTAL NEPHRITIS IN RATS INDUCED BY INJECTION OF ANTI-KIDNEY SERUM
Authors: Smadel Joseph E. , Farr Lee E.
Published: June 2004

The glomerulonephritis induced in rats by nephrotoxin was characterized clinically during its initial phase by severe albuminuria, cylindruria, and anasarca, but not by hematuria.

Rapidly fatal nephritis was produced by injecting relatively large amounts of anti-kidney serum at frequent intervals. In such cases the blood urea mounted rapidly; the urea clearance fell; and death occurred within about 2 weeks.

A milder nephritis of the chronic type was induced by giving smaller quantities of anti-kidney serum in either single or divided doses. In these instances there was no immediate alteration of the urea clearance. Lipemia and plasma protein deficit appeared with the development of anasarca. The majority of rats which survived the initial stage of this experimental nephritis continued to show marked albuminuria with casts until they died or were sacrificed months later. Some of these animals showed retardation of growth and a progressive fall of the urea clearance. Terminally there developed marked retention of urea, plasma protein deficit, anemia, and hypertension.
EXPERIMENTAL NEPHRITIS IN RATS INDUCED BY INJECTION OF ANTI-KIDNEY SERUM
Authors: Swift Homer F. , Smadel Joseph E.
Published: June 2004

A saline extract of perfused rat kidney administered intravenously to rats immediately before injecting an anti-rat-kidney serum, by the same route, prevents renal damage. A preliminary injection of physiological salt solution or of an extract of perfused rat liver has no preventive effect.

These findings are a further indication that the nephrotoxic effect induced by anti-kidney serum is dependent upon a relatively organ specific antibody, nephrotoxin.
VIRUSES OF POLIOMYELITIS
Authors: Trask James D. , Paul John R. , Beebe Agnes R. , German William J.
Published: June 2004

Qualitative immunological differences exist between early passage strains or so called human strains of the virus of poliomyelitis.

These differences show a relationship to the epidemic source of the virus and are exemplified in this study by 4 strains isolated in different years during an eastern and western epidemic of poliomyelitis.
INFECTIOUS MYXOMATOSIS OF RABBITS
Authors: Rivers Thomas M. , Ward S. M.
Published: June 2004

From the results of the experiments described in this paper it is obvious that large amounts of elementary bodies of myxoma can be obtained in a relatively pure state by means of the methods used. Furthermore, it is evident that infectious myxomatosis is a viral disease in which elementary bodies of the same order of magnitude as vaccinal elementary bodies play a conspicuous rô1e in that they either represent the etiological agent or are intimately associated with it. The bodies are specifically agglutinated by antimyxoma serum and are agglutinated to a less extent by serum from rabbits convalescing from fibroma, a disease closely related to myxoma. In virus-free filtrates of emulsions prepared from infected skin there is a soluble precipitinogen or precipitinogens specific for the malady. Moreover, a specific precipitinogen or precipitinogens are demonstrable in virus-free serum of animals acutely ill as a result of extensive infection with myxoma virus. It is believed that this is the second viral disease, yellow fever (14) being the first, in which a specific soluble antigen free from virus has been found in the serum of ill animals.
INFLUENCE OF HOST FACTORS ON NEUROINVASIVENESS OF VESICULAR STOMATITIS VIRUS
Authors: Sabin Albert B. , Olitsky Peter K.
Published: June 2004

1. Injection of vesicular stomatitis virus into the leg muscles of young mice gives rise to flaccid paralysis of the inoculated extremity as the first clinical sign of a disease which is invariably fatal; old mice similarly injected with the largest doses of virus survive without exhibiting any signs of illness.

2. In young mice the virus was shown to multiply at the site of inoculation and to invade the sciatic nerve and spinal cord; there was no evidence of multiplication of virus in the blood or viscera.

3. In old mice, after intramuscular injection of as much as 10 million M.C.L.D., there was no evidence of either local or systemic multiplication; in spite of the persistence of thousands of M.C.L.D. of virus at the site of inoculation for at least 4 days, there was no detectable invasion of the sciatic nerve or the central nervous system.

4. Injection of the virus directly into the sciatic nerve of old mice led to the typical paralytic disease in half the number of animals.

5. For 3 days after intrasciatic injection the virus could be demonstrated in the nerve but not in the spinal cord or brain. At the onset of paralysis (6th day) virus was detectable in the spinal cord but no longer in the inoculated nerve.

6. The capacity of the virus to invade the central nervous system from the nerve but not from the muscle suggested the existence of a barrier in the muscle or myoneural junction.

7. Injection of the virus into the vitreous humor of the eye is followed by a fatal encephalitis in 15 day old mice, but 1 year old mice, with few exceptions, survive without showing signs of disease.

8. The spread of virus in the brains of intraocularly injected, 15 day old mice was too rapid to indicate the pathways which were pursued, but in 21 day old mice there was evidence that the primary pathway was probably along the axons of the optic nerve with decussation to the contralateral diencephalon and mesencephalon, and subsequent early spread to the corresponding occipital cortex. In resistant, old mice, however, no virus was found in any part of the brain.
THE EFFECT OF HEMOPHILUS INFLUENZAE SUIS VACCINES ON SWINE INFLUENZA
Authors: Shope Richard E.
Published: June 2004

Either living or heat-killed H. influenzae suis vaccines, given intramuscularly to swine, elicit an immune response capable of modifying the course of a later swine influenza infection. The protection afforded is only partial and is in no way comparable to the complete immunity afforded by swine influenza virus vaccines.
ELEMENTARY BODIES OF VACCINIA FROM INFECTED CHORIO-ALLANTOIC MEMBRANES OF DEVELOPING CHICK EMBRYOS
Authors: Smadel Joseph E. , Wall M. J.
Published: June 2004

By a method of differential centrifugation and tryptic digestion suspensions of elementary bodies have been prepared from chorioallantoic membranes of chick embryos infected with vaccine virus. The infective titer of the final suspension of elementary bodies was usually the same as that of the original tissue emulsion. Elementary bodies from infected chick membranes were agglutinated as well by antivaccinal serum obtained from different mammalian species as were bodies prepared from inoculated rabbit skin. Seitz filtrates of infected chick material contained soluble precipitable substances of vaccinia; these filtrates and filtrates from infected rabbit skin, respectively, reacted equally well with rabbit serum which contained either L or S antibodies.
EXPERIMENTAL LOCAL BLADDER EDEMA CAUSING URINE REFLUX INTO URETER AND KIDNEY
Authors: Auer John , Seager Lloyd D.
Published: June 2004

Experimental infiltration of the intravesical ureter of the normal bladder in the living, anesthetized animal with magnesium sulfate or physiological salt solution caused a reflux of urine into the ureter in 6 out of 18 guinea pigs (33 per cent); in 22 out of 27 rabbits (81 per cent), and in 14 out of 17 dogs (82 per cent).

The vesical pressure necessary to produce this experimental reflux is low and ranges between 2 and 12 mm. of Hg; hydrostatic pressure of the bladder contents often sufficed to drive urine into the kidney pelvis.

After an experimental reflux had occurred, increased vesical pressure often failed to raise the level of the regurgitant column in the ureters of rabbit and dog: these higher pressures had rendered an incompetent valve competent.

Control pressures ranging between 8 and 40 mm. of Hg without a preceding infiltration, caused no reflux in the great majority of dogs.

The amount of infiltrated fluid necessary to produce reflux varied from 0.2 cc. in the guinea pig to 0.5 to 2 cc. in dog.

Spontaneous regurgitation, that is regurgitation without a preceding infiltration, was seen in 4 guinea pigs, 4 rabbits and 2 dogs.

Antiperistalsis of the ureters, that is a wave of contraction passing from the bladder to the kidney, was never seen in our animals with experimental reflux.

Biopsy of the bladder in rabbit and dog showed edema of the ureterovesical valves after infiltration in most of our animals. Hemorrhages into the submucosa in the neighborhood of the ureteral valves were observed in some. The bladders of 3 rabbits, exhibiting spontaneous reflux without infiltration showed pouting, edematous lips of the ureterovesical orifices.

The cause of experimental regurgitation is a non-obstructive edema of the vesical valve; this edema renders the valve flap more rigid and therefore incompetent at relatively low intravesical pressures. Higher intravesical pressures may again render the incompetent valve competent.

The experimental results are applied to the human subject because the urinary bladder of dog and of man are quite similar in structure and function. Reasons are presented suggesting that the described type of reflux may cause pyelitis and pyelonephritis.
STUDIES ON INFLAMMATION
Authors: Menkin Valy
Published: June 2004

There is present in inflammatory exudates a factor which induces a prompt increase in the permeability of normal capillaries. Its liberation and presence in exudates offers a reasonable explanation for the mechanism of increased permeability of small vessels in injured tissue.

A method for the isolation and purification of this permeability factor has been described. In its essential features, this consists of treating the exudate with pyridine followed by acetone. After separation of the protein fractions further purification can be obtained by prolonged extraction with butyl alcohol or by subjecting the acetone supernatant fraction to low temperature (–20°C.). The latter favors spontaneous separation of the active principle. The purified material is a crystalline doubly refractive nitrogenous substance.

The factor is evidently not a protein, yet it contains amino and carboxyl groups. It gives a positive test for the presence of an indole nucleus in its structure (Adamkiewicz test). The active material is dialyzable; and it is precipitated by concentrated ammonium sulfate. The present evidence indicates that it is an intermediary breakdown product of protein metabolism, probably belonging to the group of relatively simple polypeptides. Further studies are being conducted in an endeavor to determine its precise chemical structure.
STUDIES ON INFLAMMATION
Authors: Menkin Valy
Published: June 2004

Blood serum digested by trypsin yields split products which, when injected into the skin of normal rabbits, rapidly increase the permeability of small cutaneous vessels. This is likewise followed in the affected tissue by prompt local migration of polymorphonuclear leukocytes.

The tryptic digest of blood serum can be purified by methods previously described (3). The resulting crystalline substance alters the permeability of the capillary wall and favors local migration of leukocytes in a manner similar to leukotaxine proper. The present observations indicate that leukotaxine, or a substance having at least identical biological properties, appears to have been formed by proteolytic enzymatic action on an otherwise relatively inactive blood serum. This finding serves as additional evidence in support of the view that leukotaxine, recovered from inflammatory exudates, is probably an intermediary product of protein catabolism.
HEMOGLOBIN PRODUCTION IN ANEMIA AS INFLUENCED BY THE BILE FISTULA
Authors: Hawkins W. B. , Robscheit-Robbins F. S. , Whipple G. H.
Published: June 2004

The presence of a renal bile fistula with escape of all bile into the urinary tract seriously impairs the capacity of an anemic dog to form new hemoglobin on standard diets.

These bile fistula dogs will produce about one-half as much hemoglobin in anemia on standard diets as during earlier control periods without a bile fistula.

Iron given by mouth to an anemic bile fistula dog will effect the production of about one-half the amount of new hemoglobin as in control periods.

Iron given by vein to an anemic bile fistula dog will approximate the theoretical 100 per cent return of new hemoglobin. Obviously absorption is a very important factor in the utilization of iron by these dogs.

The reaction to liver feeding is much like the reaction to iron feeding but we have no proof of inadequate protein digestion and absorption in these bile fistula dogs.

In fact the uniform body weight and normal clinical state over periods of years speak for adequate absorption of protein digestion products. Evidence cited above supports our belief that inadequate hemoglobin production (protein formation) noted in these bile fistula dogs may be related to a disturbed liver function.
HYDROGEN ION CONCENTRATION IN EXUDATES OF PNEUMOCOCCUS INFECTION
Authors: Kelley William H. , Scadron E. N. , Shinners B. M.
Published: June 2004

The hydrogen ion concentration in the lesions of experimental pneumococcus infection has been estimated directly by pH determinations on exudates from living animals. For indirect evidence of an increase in hydrogen ion concentration within the lesions, the difference in sugar content between exudate and blood from animals with pneumococcus infection has been measured.

With sanguinous exudate from the consolidated lungs of dogs with experimental pneumococcus pneumonia, the findings were not always consistent, but usually there was either direct or indirect evidence of increased hydrogen ion concentration. The physicochemical changes in exudate from animals treated with artificial pneumothorax showed no important differences from those in other specimens. In concurrence with Lord's (1, 2) observation of increased acidity in pneumonia exudate obtained at autopsy, sugar concentrations, which are low in the blood, were markedly reduced in exudates from animals which had died of the infection.

Serous exudates from dermal pneumococcus infection in rabbits uniformly showed definite acidity by both direct and indirect methods of estimation. The hydrogen ion concentrations in exudate from dermal pneumococcus infection in rabbits varied between pH 6.87 and 6.66 but were not always proportional to the difference in sugar concentrations between the exudate and blood. While these hydrogen ion concentrations are similar to those attained in the pneumonic exudate from dogs, they are of lesser magnitude than those which Takahashi (3) has described in the pus of secondary empyema due to the pneumococcus.
THE COMPLEMENT FIXATION REACTION IN MONKEY MALARIA
Authors: Coggeshall Lowell T. , Eaton Monroe D.
Published: June 2004

1. A specific complement fixation reaction test for Plasmodium knowlesi malaria in rhesus monkeys is reported with details involved in the preparation of the antigen and procedures employed in setting up the test.

2. It was found that specific complement-fixing antibodies appeared early in the course of the experimental disease and persisted during the course of the chronic infection.

3. The first appearance of complement-fixing antibodies was generally followed by a temporary fall in titer. During the first 2 months of infection there was no apparent relationship between the number of circulating parasites and the changes in complement fixation titer.

4. During the stage of chronic infection there was a fall in the titer of complement-fixing antibodies preceding each parasitic relapse, and after the relapse had terminated, there was an elevation of the complement-fixing titer.
THE FATE OF VACCINIA VIRUS ON CULTIVATION IN VITRO WITH KUPFFER CELLS (RETICULO-ENDOTHELIAL CELLS)
Authors: Beard Joseph W. , Rous Peyton
Published: June 2004

The pathogenic activity of vaccinia virus is in large part suppressed when it is mixed with living Kupffer cells or clasmatocytes in the test-tube and injected intradermally.

Vaccinia increases in quantity when introduced into cultures of Kupffer cells in vitro, and survives in immediate association with these elements. No antiviral principle is elaborated by them under such conditions.
A METHOD FOR DETERMINING THE DIFFERENTIAL SEDIMENTATION OF PROTEINS IN THE HIGH SPEED CONCENTRATION CENTRIFUGE
Authors: Hughes Thomas P. , Pickels Edward G. , Horsfall Frank L.
Published: June 2004

A method is presented for determining the relative degree of sedimentation of proteins and other small particles, either in pure form or in a mixture, utilizing the concentration centrifuge of Bauer and Pickels. Chemical analysis or biological assay of material obtained at different fluid levels by means of a special sampling device is used to measure the degree of sedimentation. The results are reproducible within 10 per cent and, under the conditions of the experiments cited, are characteristic for the proteins thus far investigated.
THE QUANTITATIVE RELATIONSHIP BETWEEN IMMUNE SERUM AND INFECTIVE DOSE OF PARASITES AS DEMONSTRATED BY THE PROTECTION TEST IN MONKEY MALARIA
Authors: Coggeshall Lowell T. , Eaton Monroe D.
Published: June 2004

The minimal infective dose of Plasmodium knowlesi for rhesus monkeys was found in this study to be between 1 and 10 parasites when injected intraperitoneally. As the dose of parasites is increased, the length of time prior to the appearance of circulating parasites is decreased. However, the severity of the infection once it is established is independent of the initial dose of parasites.

In passive protection experiments a quantitative relationship was demonstrated between the number of parasites in the inoculum and the effective amount of immune serum given at the time of infection and in equal doses daily for 9 days thereafter. The smaller the inoculum, the less the quantity of immune serum required to prevent the death of the animal.

When relatively large amounts of immune sera and small numbers of parasites were used in the protection experiment, infection was prevented.
FATE OF NASALLY INSTILLED POLIOMYELITIS VIRUS IN NORMAL AND CONVALESCENT MONKEYS WITH SPECIAL REFERENCE TO THE PROBLEM OF HOST TO HOST TRANSMISSION
Authors: Sabin Albert B. , Olitsky Peter K.
Published: June 2004

With a method of intranasal instillation of poliomyelitis virus that brings about infection of all M. rhesus monkeys subjected to it, a study was undertaken of the fate of nasally instilled virus in normal and convalescent, immune animals. Control experiments revealed that nasal mucosa of normal monkeys contained no observable antiviral factors and that when five or ten minimal cerebral infective doses were added to the mucosa, virus could be detected by the employed procedure. In the olfactory bulbs even a single infective dose could be recovered, since suspensions of both bulbs could be transferred to the brain of a monkey without any loss of material.

After nasal instillation of virus in normal monkeys, it disappeared quickly (4 hours or less) and could be recovered neither from the excised nasal mucosa nor from the olfactory bulbs during the first 48 hours. At 72 hours, just before or coincident with the first rise of temperature, virus was found in very small amounts in the nasal mucosa and for the first time also in the olfactory bulbs. At 96 hours, at least 3 days before the appearance of nervous signs, and later, while virus continued to be present in considerable amounts in the olfactory bulbs (and presumably elsewhere in the central nervous system), none was detected in the nasal mucosa. In convalescent, immune animals receiving the same strain of virus intranasally which caused the original infection, none could be recovered from the nasal mucosa or central nervous system at 4 hours, 1, 2, 3, 4, 5, and 7 days. The bearing of these observations on the problem of host to host transmission of poliomyelitis virus is discussed.
CARCINOMA IN THE LEOPARD FROG: ITS PROBABLE CAUSATION BY A VIRUS
Authors: Lucké Balduin
Published: June 2004

An epithelial tumor with acidophilic intranuclear inclusions frequently occurs in the kidneys of leopard frogs. This tumor usually has the appearance of an infiltrating and destructive adenocarcinoma, which, when large, not uncommonly metastasizes; less often it is more orderly and adenomatous.

When inoculated as living fragments or cell suspensions into the lymph sacs, the cranial cavity, or the abdomen, no significant local growth results and the implanted material is resorbed. However, in approximately 20 per cent of the frogs surviving inoculation for more than 6 months, tumors develop in the kidney, which are like the "spontaneous" neoplasms. The incidence far exceeds that in the controls.

Desiccated and glycerinated tumor injected into the abdomen gives the same result as inoculation with living tumor; in somewhat over 20 per cent of animals surviving more than 6 months kidney tumors occur.

In alien species of frogs, no such tumors are produced by inoculation either with living or with desiccated tumor.

These experiments indicate the probability that the kidney tumor of the leopard frog is caused by an inclusion-forming, organ-specific virus.
STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS
Authors: Landsteiner K. , Di Somma A. A.
Published: June 2004

With the view of making new types of chemicals accessible for investigations on drug hypersensitiveness, methods have been devised for sensitizing animals with diazomethane and mustard oil, two non-aromatic compounds.

Guinea pigs have been sensitized to diazomethane, a substance of high reactivity and known to cause severe allergic effects in man.

With the second substance, allylisothiocyanate, likewise capable of forming conjugates with substances in the animal body, sensitization effects have been obtained in man and in hogs. Sensitization in human beings was successful with one out of six individuals treated.

The observations indicate species and individual differences as regards the ability to become sensitized to various chemical compounds.
STUDIES ON EASTERN EQUINE ENCEPHALOMYELITIS
Authors: King Lester S.
Published: June 2004

The action of the virus of equine encephalomyelitis in the guinea pig brain has been studied, and various histological changes have been described in detail. After peripheral inoculation (as in the pad) the earliest detectable pathologic change in the nervous system is the accumulation of leucocytes within the lumen of blood vessels, and the proliferation of the vascular adventitia. This precedes the appearance of any significant perivascular cuffing, and may or may not be accompanied by a few polymorphonuclear leucocytes in the tissue.

The typical lesion is a fairly well circumscribed focus of polymorphonuclear leucocytes accompanying the blood vessel changes described above. The leucocytes may be numerous or sparse, and may or may not be accompanied by neuronal destruction.

In early cases, before the onset of symptoms, such circumscribed lesions appear in small number irregularly scattered through the gray matter. The neo- and olfactory cortices are the principal sites of predilection, although basal ganglia, thalamus, cerebellum, and lower olfactory centers may also be involved. The hippocampus is much less affected than other parts of the brain.

A rough distinction is made between inflammatory and degenerative lesions, a distinction which depends on the relationship between the neuronal destruction and the exudative changes in any given site. These two types are described, and their significance is discussed.

After intracerebral inoculation, the inflammatory changes are much less marked than after peripheral inoculation. This is due not to insufficient time for the development of lesions but to a different type of pathological process.

Following intracerebral inoculation, there is primary destruction of neurones, involving especially the hippocampus, and also large areas of the neo-cortex. This change, similar to ischemic necrosis, is regarded in part as a non-specific reaction of especially vulnerable tissue.
PROTECTIVE ANTIBODIES IN THE SERUM OF SYPHILITIC RABBITS
Authors: Turner Thomas B.
Published: June 2004

1. When an emulsion containing virulent Treponema pallidum is added to serum from normal rabbits and from untreated immune syphilitic rabbits that have been infected with a homologous strain of T. pallidum the mixture incubated at 37°C., and injected intracutaneously into normal rabbits, typical syphilitic lesions commonly develop at the sites of inoculation of the normal serum-spirochete mixture, while at the sites of inoculation of immune serum-spirochete mixtures usually either no lesion develops or else the incubation period of the resulting lesions is shorter and the lesions remain smaller than those produced by normal serum-spirochete mixtures.

2. In a series of preliminary experiments, of 56 areas inoculated with serum-spirochete mixtures, in 42 the suppressive action of the syphilitic serum was manifest, in 10 areas questionable evidence of protection was noted, and in 4 areas there was no evidence that the syphilitic serum had exerted a suppressive or protective action.

3. The protective action of syphilitic serum seems to have been lessened by heating to 56°C.

4. The results of the protection test in three other series of experiments were as follows: (a) Of 12 areas in 6 rabbits inoculated with normal serum-spirochete mixtures typical syphilitic lesions developed, while in the same number of areas inoculated with immune serum-spirochete mixtures there was complete or partial suppression of lesions in all. (b) Of 45 areas inoculated with serum from 10 different immune syphilitic rabbits, definite evidence of protection was observed in 37, questionable evidence in 5, and no evidence of protection in 3. (c) Of 8 areas in 4 rabbits inoculated with immune serum-spirochete mixtures no lesions developed during the period of observation, while of 8 areas in the same rabbits inoculated with one of two normal serum-spirochete mixtures typical syphilitic lesions developed in each.
CELLULAR REACTIONS TO A DYE-PROTEIN WITH A CONCEPT OF THE MECHANISM OF ANTIBODY FORMATION
Authors: Sabin Florence R.
Published: June 2004

1. The use of an antigen which can be seen within cells demonstrates that one may stimulate the phagocytic cells either of the liver and spleen or of the tissues and lymph nodes to produce antibodies.

2. The appearance of antibodies in the serum correlates with the time when the dye-protein is no longer visible within the cells and with the phenomenon of a partial shedding of their surface films.

3. It is thus inferred that the cells of the reticulo-endothelial system normally produce globulin and that antibody globulin represents the synthesis of a new kind of protein under the influence of an antigen.

4. An antigen is a substance which can specifically modify the synthesis of the cytoplasm of the cells of the reticulo-endothelial system.
PRODUCTION IN MONKEYS OF COMPLEMENT-FIXING ANTIBODIES WITHOUT ACTIVE IMMUNITY BY INJECTION OF KILLED PLASMODIUM KNOWLESI
Authors: Eaton Monroe D. , Coggeshall L. T.
Published: June 2004

Injection into rhesus monkeys of Plasmodium knowlesi killed by heat, formalin, drying, or freezing and thawing stimulates the production of complement-fixing antibodies, but no demonstrable agglutinating or protective antibodies are formed.

Possible differences in the immunity mechanisms concerned in active infection and in artificial immunization are discussed.
ESTIMATION OF THE PURITY OF PREPARATIONS OF ELEMENTARY BODIES OF VACCINIA
Authors: Smadel Joseph E. , Rivers Thomas M. , Pickels Edward G.
Published: June 2004

A method of estimating the purity of preparations of elementary bodies of vaccinia is described. It depends on the comparison of the number of infective units of virus in a given material with the number of elementary bodies. The latter figure is estimated from the dry weight of the preparation by means of a calculated value for the weight of a single dehydrated elementary body.

Values for the ratio of infective units of vaccine virus to elementary bodies varied between 1 : 2.4 and 1 : 9.2 in seven consecutive experiments; the average was 1:4.2. These ratios indicate a high degree of purity of the preparation. Moreover, they indicate that a relatively high percentage of the elementary bodies in the preparations was infective.
RADIOACTIVE IRON AND ITS EXCRETION IN URINE, BILE, AND FECES
Authors: Hahn P. F. , Bale W. F. , Hettig R. A. , Kamen M. D. , Whipple G. H.
Published: June 2004

Radioactive iron as ferrous gluconate given by vein enables us to study iron excretion in urine, bile, and feces.

There is an initial extra output in urine and feces during a few days (3 to 15 days) following the iron injection and this may total 2 to 8 per cent of the injected iron.

Following this initial reaction the urinary excretion of radio-iron drops to traces or even to zero.

The feces always contain measurable amounts of radio-iron—in five dogs receiving 100 to 250 mg. of radio-iron the fecal excretion per day settled down to 0.05 to 0.4 mg. per day.

Blood destruction (acetyl-phenylhydrazine) causes a definite increase in radio-iron eliminated in the feces (0.1 to 1.0 mg. per day). Probably most of this excess iron comes through the biliary tract (bile fistula). The bile under usual conditions contributes very little iron to the intestine (0.01 mg. radio-iron per day or less).

The body controls its iron stores by absorption or lack of it rather than by its capacity to eliminate it. The evidence is overwhelming that the dog excretes iron with difficulty and in small amounts (even in the plethoric state) by means of the biliary and gastro-intestinal tracts.
CHEMICAL AND IMMUNOLOGICAL STUDIES ON THE AGENT PRODUCING LEUKOSIS AND SARCOMA OF FOWLS
Authors: Kabat Elvin A. , Furth Jacob
Published: June 2004

The activity of the agent producing sarcoma or leukosis in material deposited by high speed centrifugation is the same as that of the original crude extracts. Material sedimentable at high speed containing approximately 10–5 mg. N produces tumors at the site of injection.

Small quantities of material sedimentable at high speed are present in normal chicken sera, and about twice as much in leukemic sera (strain 1). Normal chicken and mouse spleens and all other human and mouse tissues examined contain large amounts of material sedimentable at high speed.

Extraction of leukemic blood cells with saline yields little additional virus. The washed cells readily produce leukosis even after irradiation with amounts of x-rays sufficient to destroy the leukemic cells but not the virus.

Freezing at –60°C. preserves the activity of the high speed deposits for at least 6 months.

Addition of 5 per cent of saturated Na2SO4 solution slightly delays deterioration of high speed deposits in the ice box.

Most of the agent measured by inoculation of chickens and the fraction sedimentable at high speed measured by its nitrogen content is precipitated by one-third saturation with sodium sulfate.
STUDIES ON EASTERN EQUINE ENCEPHALOMYELITIS
Authors: King Lester S.
Published: June 2004

A fresh strain of equine encephalomyelitis virus is infectious for adult mice in high dilutions by all modes of peripheral inoculation. A fixed strain has very limited invasive power when injected peripherally unless virus is placed in fairly close contact with nerve cell bodies, as in the intranasal or intraocular routes. For fixed virus the effectiveness of the mode of inoculation may be graded in the following descending order: intracerebral, intraocular and intranasal, intravenous, intraperitoneal, intramuscular, subcutaneous.

Fixed virus has a very limited power of invading the central nervous system along the axones of peripheral nerves even when injected directly into the nerve.

Infants are more susceptible to infection than are adults. But even for infants, intraperitoneal inoculation with fixed virus is significantly less effective than similar inoculations with fresh virus.

Brain trauma does not increase the effective titer of fresh or fixed viruses but may shorten the incubation period for fresh virus. With fixed virus injected intramuscularly, a pronounced facilitating effect may be produced by the simultaneous intraperitoneal injection of 0.20 to 0.25 cc. of 50 per cent glycerine. Other irritants tried are without effect.
SEROLOGICAL TESTS FOR HOMOLOGOUS SERUM PROTEINS IN TISSUE CULTURES MAINTAINED ON A FOREIGN MEDIUM
Authors: Landsteiner Karl , Parker Raymond C.
Published: June 2004

Connective tissue cells (fibroblasts) derived from skeletal muscle of 12 day old chick embryos were cultivated for almost 8 months (35 weekly passages) in rabbit plasma and rabbit embryo tissue juice diluted with Tyrode's solution. When fluids separated from these cultures were tested with immune precipitins developed against chicken serum, they gave positive reactions which showed no tendency to diminish with an increasing number of culture generations. Barring the intervention of unknown precipitable substances, these results indicate that connective tissue can produce proteins which are identical with, or closely related to, serum proteins. The experiments further demonstrated that tissues cultivated in a foreign plasma do not lose their species specificity.
THE SPECIFICITY OF OXIDIZED AND REDUCED PROTEINS OF THE OCULAR LENS
Authors: Ecker E. E. , Pillemer L.
Published: June 2004

Oxidized and reduced proteins were prepared from the ocular lenses of sheep, swine, chicken and fish (pike). The proteins were prepared under conditions designed to avoid denaturation and to produce relatively pure compounds.

Serologic studies revealed that species specificity is demonstrable in the proteins from chicken and fish lenses, but in the more closely related species (swine and sheep) this characteristic is not so evident.

Serologic differences may be detected in the lens preparations from a single species, depending on the redox state of the protein.
III. METHOD FOR DETECTING POLIOMYELITIC VIRUS IN SEWAGE AND STOOLS
Authors: Card Sven
Published: June 2004

1. The active agent in sewage and aqueous suspensions of human stools, capable of producing poliomyelitis in rhesus monkeys after intraperitoneal inoculation, can be precipitated by 50 per cent saturation with ammonium sulfate, and no loss of activity seems to occur during this procedure.

2. The precipitated virus is not consistently "redissolvable" in water.

3. By precipitation and subsequent dialysis of the precipitate, a preparation is obtained which may be smaller in volume, and is less toxic for monkeys, than was the original material.

4. The procedure can be applied in tests on the infectivity of stools, and sewage specimens.
CHOLINE AS A MEMBER OF THE VITAMIN B2 COMPLEX
Authors: György Paul , Goldblatt Harry
Published: June 2004

The experimental rations commonly used in studies on the vitamin B2 complex are, as a rule, low in content of choline.

Addition of vitamin B6 has an aggravating influence on the specific effect of deficiency of choline, especially with regard to the development of cortical necrosis of the kidneys.

The acute and subacute lesions associated with this specific type of renal injury are described.

The renal lesions and fat infiltration of the liver, observed in rats kept on a vitamin B free diet, supplemented with thiamine, riboflavin and vitamin B6, are indistinguishable from those attributed hitherto to cystine intoxication.

Attention is drawn to the rôle of choline as a potential member of the vitamin B2 complex and, in this connection, to the importance of the ratio cystine/methionine in the diet.
PRIMARY PULMONARY COCCIDIOIDOMYCOSIS
Authors: Cronkite Alfred E. , Lack Arthur R.
Published: June 2004

1. The literature concerning inhalation infection with Coccidioides immitis is briefly reviewed.

2. A laboratory technique for exposing animals to inhalation of the spores of Coccidioides immitis is described.

3. Primary pulmonary infection was produced in 42 per cent of 72 animals exposed by this method.

4. No marked weight loss was apparent in the animals infected.

5. Skin tests with coccidioidin were not entirely satisfactory in diagnosis. Positive skin tests with coccidioidin were obtained in many of the infected animals, but inconsistencies occurred.

6. The gross and microscopic lesions are briefly described and illustrated.