bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ROLE OF ACIDURIA IN THE DEVELOPMENT OF HEMOGLOBINURIC NEPHROSIS IN DEHYDRATED RABBITS
Authors: Lalich Joseph J. , Schwartz Seymour I.
Published: June 2004

The effect of acid diets, fasting, and dehydration on the urine pH and the kidneys was determined in 11 control animals. Hyaline casts in the collecting tubules and interstitial medullary edema were observed in the 8 that survived. The test rabbits were subjected to the same treatment as the controls but, in addition, received 1.8 gm./kilo of intravenous homologous hemoglobin. Eleven of 18 animals died of hemoglobinuric nephrosis. The rabbits which died of hemoglobinuric nephrosis exhibited significant alterations in two or more of the following: kidney weight, pigment cast accumulation, and elevations of NPN.

The theories which have been advanced to explain the pathogenesis of hemoglobinuric nephrosis are evaluated in the light of the present observations. It is proposed on the basis of them that antecedent tubular damage is of primary importance in the pathogenesis of hemoglobinuric nephrosis.
ON THE NATURE OF THE TOXIC COMPONENT OF THE SOMATIC ANTIGEN OF SHIGELLA PARADYSENTERIAE TYPE Z (FLEXNER)
Authors: Tal Chloe , Goebel Walther F.
Published: June 2004

From the chemical evidence presented it appears that the toxicity associated with the somatic antigen of Type Z Sh. paradysenteriae may be attributed to an entity distinct from the known components of the complex. That this substance is neither the protein, the lipid, nor the carbohydrate component of the antigen is evident. Because of its lability to chemical manipulation, the nature of the toxic component, has not yet been ascertained.
THE ACTIVATING EFFECT OF CALCIUM ON A BACTERICIDAL SUBSTANCE FOR BACILLUS SUBTILIS IN HUMAN SERUM
Authors: Jacox Ralph F.
Published: June 2004

An enhanced bactericidal activity of human serum for B. subtilis develops during many different forms of illness, e.g. carcinoma, virus and bacterial infections, and during acute coronary occlusion.

This increased bactericidal effect cannot be related to leucocytosis, fever, serum complement, C-reactive protein, or a specific antibody reaction.

The serum bactericidal factor becomes inactive in decalcified serum, but active again when optimal concentrations of calcium are added. Magnesium does not cause reactivation.
LESIONS CAUSED IN SUCKLING MICE BY CERTAIN VIRUSES ISOLATED FROM CASES OF SO CALLED NON-PARALYTIC POLIOMYELITIS AND OF PLEURODYNIA
Authors: Pappenheimer Alwin M. , Daniels Joan B. , Cheever F. S. , Weller T. H.
Published: June 2004

A study has been made of the lesions produced in suckling mice by the following viruses: Powers, Matulaitis, DeMole, Kine, McCarthy, Conn. 5, Ohio R, High Point, WS No. 4, EMC, and Col. SK.

Pathologic alterations have been found in myocardium, lungs, liver, pancreas, thymus, brain and spinal cord, adipose tissue, and skeletal muscles.

A comparison of the lesions produced by the individual strains has disclosed certain differential features which are discussed in detail. Within the group of so called Coxsackie viruses, myositis has not proved to be a constant finding, and it may occur in suckling mice infected with other types of virus.
THE PURIFICATION AND PROPERTIES OF STREPTOLYSIN S
Authors: Cinader Bernhard , Pillemer Louis
Published: June 2004

Considerable purification of streptolysin S has been achieved by fractionation of crude bacterial filtrates with methanol, under controlled conditions of pH, ionic strength, and temperature. The final material (P III) consisted of two electrophoretic components.

The purified material was employed for kinetic studies, the results of which were confirmed with hemolysin isolated electrophoretically from P III.

The heat of activation (temperature characteristic) of streptolysin S was found to be 17,900 calories per mole.

Time dilution curves of the hemolysin were found to be sigmoid.

The influence of certain ions and lipids on the course of hemolysis was investigated.

The significance of the prolonged lag period and of the deviation in the behavior of streptolysin S from Ponder's equation has been discussed.
STUDIES ON THE LIFE CYCLE OF SPIROCHETES
Authors: DeLamater Edward D. , Wiggall Richter H. , Haanes Merle
Published: June 2004

Further evidence for the occurrence of a complex life cycle in the pathogenic Treponema pallidum as visualized by means of stained preparations is presented.
STUDIES ON THE EXTRACELLULAR CULTIVATION OF AN INTRACELLULAR PARASITE (AVIAN MALARIA)
Authors: Trager William
Published: June 2004

The erythrocytic stages of Plasmodium lophurae were freed from their host red cells by specific hemolysis directly into a favorable medium containing an extract of duck erythrocytes. Extracellular survival and development of the parasite in vitro occurred in culture media consisting essentially of a very concentrated extract of duck red cells prepared in a special nutrient solution. Omission or dilution of the red cell extract resulted in rapid degeneration of the parasites. Their survival and development were favored by the presence in the erythrocyte extract of gelatin, yeast adenylic acid, and cozymase, and especially by the further addition of adenosinetriphosphate and sodium pyruvate. Under the best conditions yet tested, all the free parasites continued their development extracellularly during the first two days of cultivation. Merozoites formed by the extracellular segmentation of the free parasites originally present developed further into trophozoites. On the third day a majority of the free parasites were still of normal appearance, but by the fourth day more were degenerate, and very few normal parasites remained on the fifth day.
EXPERIMENTAL CONGENITAL TOXOPLASMOSIS
Authors: Cowen David , Wolf Abner
Published: June 2004

Toxoplasmosis can be transmitted to mice by the introduction of Toxoplasma into the vagina. Pregnant mice were more susceptible to infection than non-pregnant animals in the ratio of 3 to 1. Obvious signs of vaginitis were not observed. Many of the infected mice remained entirely free of external signs, while a minority showed neurological or respiratory disturbances. Pregnant animals, especially those infected 6 to 10 days following conception, often died in the terminal stages of pregnancy or shortly after parturition. The possibility that the vagina may serve as one of the portals of entry of Toxoplasma in the human being and that infection may occur by sexual contact or by contamination by feces or other Toxoplasma-containing materials is discussed. The high susceptibility of the pregnant mouse to toxoplasmosis under the conditions of these experiments suggests a possible explanation for the higher incidence of congenital as compared to postnatal human toxoplasmosis and for the associated asymptomatic maternal infection. The infected but clinically normal human mothers may be compared to some vaginally infected pregnant mice which remained symptom-free.
IMMUNOLOGICAL REACTIONS OF THE COXSACKIE VIRUSES
Authors: Kraft Lisbeth M. , Melnick Joseph L.
Published: June 2004

The preparation of complement-fixing antigens for the Coxsackie group of viruses (C virus) is described. This includes the manufacture of crude antigens, their subsequent treatment with protamine sulfate to remove non-specific interfering substances, and their concentration by ultracentrifugation.

The plate complement fixation technique of Fulton and Dumbell is described in detail as it has been used for the Coxsackie viruses.

Seven strains of C virus have been cross-tested in the plate complement fixation test and have been found to belong to six immunologically distinct types.

The temporal pattern of complement-fixing antibodies in human beings infected with two types, Ohio-1 and Easton-2, respectively, has been studied. In the former the antibodies rise to a peak rather late in convalescence (3rd month) and in the latter, complement-fixing antibodies are already present at high levels in the acute phase serum. The problems of serodiagnosis are briefly discussed.
THE LYMPHOCYTIC ORIGIN OF A PLASMA FACTOR RESPONSIBLE FOR HYPERSENSITIVITY IN VITRO OF TUBERCULIN TYPE
Authors: Miller Joseph M. , Favour Cutting B. ,   With the Technical Assistance of Merle A. Umbarger and Barbara A. Harrison
Published: June 2004

Methods are described for the evaluation in vitro of the effect of tuberculin on the leucocytes of peripheral blood.

Washed leucocytes from a tuberculin sensitive host suspended in normal plasma are not lysed by tuberculin until after several hours of contact.

Washed leucocytes from a tuberculin-sensitive host slowly release into normal plasma a factor which will cause the lysis of normal leucocytes exposed to tuberculin.

Dialysis of normal plasma containing shed plasma factor causes the latter to precipitate with the euglobulins.

Shed plasma factor can be recovered from normal plasma which has been incubated with lymphocytes from tuberculin-sensitive hosts. Suspensions of neutrophils do not yield shed plasma factor.
THERAPY OF INFECTION WITH PNEUMONIA VIRUS OF MICE (PVM)
Authors: Ginsberg Harold S. , Horsfall Frank L.
Published: June 2004

Inhibition of the multiplication of PVM by the capsular polysaccharide of Friedländer bacillus, type B, is associated with restriction in the development of pneumonia induced with the virus in the mouse lung. The extent of the pneumonic process appears to be a function of the degree of viral multiplication; the greater the inhibition of multiplication, the less extensive is the pneumonia and the more probable is the recovery of animals treated with the polysaccharide. Effective therapy of pneumonia induced in mice with PVM is obtained with a single injection of 0.02 mg. of the substance given intranasally either 2 or 3 days after inoculation. Under appropriate conditions, treated animals recover completely from a viral infection which is, in control animals, uniformly fatal.

The polysaccharide produces inhibition if given in the first two-thirds of the latent period of the multiplication cycle, i.e., within 10 hours, but is ineffective when given at 12 hours or later. However, the second cycle and subsequent cycles are inhibited irrespective of the time the substance is injected during the first cycle of multiplication. The findings are discussed in relation to a theory regarding the mechanism of action of the polysaccharide.
THE BEHAVIOR OF RESIDUAL AXONS IN PARTIALLY DENERVATED MUSCLES OF THE MONKEY
Authors: Edds Mac V. , Small Wilfred T.
Published: June 2004

Leg muscles of the monkey have been studied following partial denervation produced by surgical elimination of from 25 to 90 per cent of the axons entering the sciatic nerve from the lumbosacral plexus. The investigation included observations on function, rate and degree of muscle atrophy, and neurohistological appearance of the affected muscles.

In most of the cases, from 83 to 90 per cent of the residual nerve fibers in the peroneal and tibial nerves were destroyed and a severe paresis of the leg muscles was produced. No functional improvement was noted up to 160 days after operation, and the affected muscles became markedly atrophic. Histological examination of these muscles failed to reveal more than sporadic collateral regeneration of the residual axons.

In two cases 50 and 75 per cent of the peroneal and tibial nerve fibers remained intact 63 and 200 days, respectively, after operation. The legs operated upon in these cases functioned almost normally and all muscles weighed within 11 per cent of those of the contralateral, normal leg. Histological study and counts of end-plate: nerve fiber ratios showed that many residual axons had regenerated collateral branches which entered denervated end-plates. Collateral regeneration was incomplete, however, and many end-plates remained without innervation.

These results indicate that residual axons in paretic muscles of a primate do not regenerate collaterally as readily as do those of other previously studied mammals.
DETERMINATION OF INHERITED TRAITS OF H. INFLUENZAE BY DESOXYRIBONUCLEIC ACID FRACTIONS ISOLATED FROM TYPE-SPECIFIC CELLS
Authors: Alexander Hattie E. , Leidy Grace
Published: June 2004

Change of non-typable (R) strains of H. influenzae into the specific type of origin or new types (S) has been effected in vitro in a predictable fashion within a single 24 hour growth period, by a desoxyribonucleic acid-containing fraction isolated from type-specific cells of the type desired.

Only a small proportion of the population of R cells are susceptible to the change induced in inherited characteristics by the desoxyribonucleic acid fraction. The data suggest that the number of susceptible cells present in any given population size varies with the specific type of origin of the R cells; a lesser degree of variation in different independent cultures of the same strain and population size has been demonstrated. The results suggest that the R H. influenzae cells which are susceptible to transformation arise as the result of mutation.

It has been demonstrated that the reaction necessary for transformation takes place virtually immediately if susceptible cells are present. Furthermore it has been shown that the change which enables an R cell to form a colony of type-specific organisms has been completed within 15 minutes in an environment which does not permit cell multiplication.
RADIOAUTOGRAPHIC VISUALIZATION OF SULFUR-35 DISPOSITION IN THE ARTICULAR CARTILAGE AND BONE OF SUCKLING RATS FOLLOWING INJECTION OF LABELED SODIUM SULFATE
Authors: Dziewiatkowski Dominic D.
Published: June 2004

The localization of sulfur-35 administered intraperitoneally as sodium sulfate to 7-day-old rats was determined by radioautography of sections of humeri and tibia-knee-femur combinations removed 24, 48, 96, 216, and 290 hours after injection of this isotope.

Radioautography of sections of bone and cartilage that had been fixed in formalin indicated that the tracer isotope was present throughout the entire epiphysis. Its concentration therein was highest initially at the epiphyseal-diaphyseal junction where the more mature cartilage cells were present.

By the 96th hour post injection the sulfur-35 had become more uniformly distributed in the epiphyses and an even distribution of it throughout the epiphyseal cartilage was almost attained by the 216th hour post injection.

As centers of secondary ossification arose in the epiphyseal cartilage, the sulfur-35 appeared to diminish in concentration and disappear from these loci. However, radioautographs of cartilage fixed in formalin saturated with barium hydroxide, instead of in formalin only, disclosed the fact that the tracer isotope was still present in these loci.

When bone and bone marrow were fixed in formalin the autographs indicated the presence of sulfur-35 primarily in the periosteum. Only a negligible amount appeared to be present in the bone shaft and marrow. However, when these tissues were fixed in formalin saturated with barium hydroxide it was possible to demonstrate the presence of the tracer isotope in both bone and bone marrow.
CONVERSION OF PLASMA PROTEIN TO TISSUE PROTEIN WITHOUT EVIDENCE OF PROTEIN BREAKDOWN
Authors: Yuile C. L. , Lamson B. G. , Miller L. L. , Whipple G. H.
Published: June 2004

Labeled plasma proteins obtained from donor dogs, previously fed ϵ-C14-dl-lysine, have been given intravenously to recipient dogs.

The disappearance of labeled globulin from the plasma at a rate considerably faster than albumin has been confirmed.

Evidence suggesting that the mass of protein in solution in the extravascular, extracellular fluid is approximately equal to the plasma proteins in circulation has been derived from a study of the dilution of labeled plasma protein by repeated injections of non-labeled plasma protein.

In a period of 7 days the transfer of C14 from plasma to tissue proteins amounted to between 30 and 40 per cent of the activity in the labeled plasma protein injected intravenously. The conversion was accompanied by a very small loss of activity in the urine and expired air and the activity remained in the lysine residue of the liver and probably of other tissues.

The data presented favor the view that plasma proteins are utilized in the body economy after partial catabolism within the cell area and provide no evidence of complete breakdown to the amino acid level.
CYTOCHEMICAL STUDIES ON THE KIDNEY
Authors: Kurnick N. B.
Published: June 2004

Determinations of the desoxyribonucleic acid (DNA) content of the kidneys of growing rats were made on the whole tissues and on isolated nuclei. It was found that the DNA content per nucleus is constant in rats of different weights. The DNA content of the kidneys increased proportionately to their mass over the range studied. It is concluded that increase in mass is primarily due to cell multiplication.
STUDIES ON ENDEMIC PNEUMONIA OF THE ALBINO RAT
Authors: Nelson John B.
Published: June 2004

A colony of albino rats was developed from three breeders (not germ-free) originally delivered by Cesarian section and artificially reared in the laboratories of Professor James A Reyniers.

The colony has been maintained under quarantine since June, 1948, in the absence of any demonstrable involvement of the respiratory tract or of the middle ears.

At autopsy pleuropneumonia-like organisms, Streptobacillus moniliformis, and the virus-like agent associated with endemic pneumonia were not recoverable from the lungs or the nasal passages of 81 young and adult rats.

During the same time interval the morbidity rate of pneumonia in another rat colony known to be free from infectious catarrh was 51 per cent while the incidence of infection with the virus-like agent approached 100 per cent.
THE INFLUENCE OF CORTISONE ON PRIMATE MALARIA
Authors: Schmidt L. H. , Squires Wanda L.
Published: June 2004

Studies have been made of the effects of cortisone on the course of primary and developed infections with P. cynomolgi in the rhesus monkey. This investigation has shown that repetitive admmistration of the hormone in daily doses of 10 mg. per kg. during the primary attack produced striking intensification of the peripheral blood infection during the postcrisis phases of the disease. Similar administration of 10 or 50 mg. per kg. doses of the hormone during the chronic or latent stages of the infection provoked recrudescences of remarkable severity. In both early and late infections the responses induced by cortisone treatment corresponded closely to the reactions to splenectomy.

Collateral studies have shown that the doses of cortisone which produced the reactions described above also evoked a lymphopenia, marked reductions in the sizes of the axillary and inguinal lymph nodes and spleen, and striking histological changes in the latter organ. These changes involved severe regression or exhaustion of lymphoid elements in both splenic nodules and pulp with almost complete obliteration of proliferative activities involved in the production of macrophages from lymphocytes. Indications are that the resulting reduction in supply of macrophages, rather than inhibition of phagocytic activity per se, was responsible for the intensification of the disease produced by cortisone.
STUDIES ON THE AGENT OF INFECTIOUS HEPATITIS
Authors: Drake Miles E. , Ward Charles , Stokes Joseph , Henle Werner , Medairy George C. , Mangold Françoise , Henle Gertrude
Published: June 2004

At the onset of an epidemic in a closed institution about one-fourth of the inmates were skin-tested. During the year following the skin test, 5 cases of hepatitis with jaundice were recorded among 320 skin-tested individuals with unknown histories, one in the 144 skin test-positive, and 4 in the 176 skin test-negative subjects. In contrast 112 cases occurred among the 825 non-skin-tested individuals. Thus, the incidence of jaundice in the skin-tested group was 1.6 per cent as against 13.6 per cent in the non-skin-tested individuals. Possible explanations for this observation have been discussed.
THE ISOLATION AND IDENTIFICATION OF PARA-AMINOBENZOIC ACID PRODUCED BY STAPHYLOCOCCI RESISTANT TO SULFONAMIDE
Authors: Leskowitz Sidney , Fox Charles L. , Raymond Samuel
Published: June 2004

Previous studies have shown that when Staphylococcus aureus becomes resistant to sulfonamides, an antisulfonamide substance is produced in the growth medium. Although these studies suggested that the substance was p-aminobenzoic acid (PABA), isolation and positive identification were not achieved. Because of the importance of these observations, unequivocal identification of the product was attempted.

A strain of Stapkylococcus aureus resistant to sulfonamides was cultivated on a simplified medium, the organisms separated in a Sharples centrifuge and the diazotisable amine absorbed on amberlite IR-120 previously acidified. Elution was accomplished with pyridine and the amine recovered by ether extraction at pH 3.7. Paper chromatography revealed one amine resembling PABA and another contaminating diazotizable amine present in very small amounts. The PABA-like amine was further separated by chromatography; its Rf value and its spectrum in the ultraviolet then equalled those obtained with PABA. A 2,4-dlnltrophenyl derivative of the amine was prepared and the m.p. was similar to that of the derivative made from PABA.

On the basis of the physical and chemical properties described, it would appear unequivocal that this bacterial amine is PABA.
FUCHSINOPHILE GRANULES IN THE TISSUES OF MICE INFECTED WITH THE CONNECTICUT-5 STRAIN OF COXSACKIE VIRUS
Authors: PAPPENHEIMER Alwin M.
Published: June 2004

Minute cytoplasmic fuchsinophilic granules, characteristically surrounded by a halo, have been demonstrated in the lesions produced in suckling mice by the Connecticut-5 strain of Coxsackie virus. Their possible significance is discussed.
ALTERATION OF EXPERIMENTAL POLIOMYELITIS INFECTION IN THE SYRIAN HAMSTER WITH THE AID OF CORTISONE
Authors: Shwartzman Gregory , Fisher Alice
Published: June 2004

Cortisone produces a significant enhancement of infection with MEF1 and Lansing strains of poliomyelitis virus in the Syrian hamster. The enhancement manifests itself in increased severity of symptoms, shortening of the incubation period, marked reduction in survival time and a high mortality rate.

The effect of cortisone is protracted, the duration depending on the dose used. There is a reciprocal relationship between the dose of cortisone and the amount of virus, the larger the dose of the hormone, the smaller the amount of virus being necessary to produce the infection. An amount of virus of low infectivity causes amarked disease with a high mortality rate in hamsters receiving a single injection of 3 mg. of cortisone, while a dose as small as 2 mg. gives a highly fatal disease with a stronger concentration of the virus.

There is a 2 log increase in the concentration of the virus in cortisone-treated hamsters.

Hamsters from various sources seem to respond differently to the enhancing effect of cortisone, one breed showing no enhancement of the infection with the Lansing strain.

Hormones other than cortisone, i.e., DCA, progesterone, diethylstilbestrol, and fast and slow acting ACTH injected repeatedly fail to modify the poliomyelitis infection in the hamster.
IMMUNOCHEMICAL STUDIES OF ANTITOXIN PRODUCED IN NORMAL AND ALLERGIC INDIVIDUALS HYPERIMMUNIZED WITH DIPHTHERIA TOXOID
Authors: Kuhns William J. , Pappenheimer A. M.
Published: June 2004

1. The immunological properties of two contrasting types of human antisera, each containing a high titer of diphtheria antitoxin, have been investigated.

2. Sera which contain only non-precipitating antitoxin exhibit most of the properties of atopic reagin-containing sera. This type of antitoxin is capable of sensitizing normal human skin to toxin or toxoid and remains for many weeks in the injected area. It exhibits no Danysz effect, does not fix complement unless very large amounts of serum are used, and can be specifically coprecipitated by addition of precipitating antitoxin and toxin. On the other hand, it is capable of sensitizing guinea pigs to fatal anaphylactic shock. Heating at 56°C. for 4 hours destroys the skin-sensitizing properties and results in almost quantitative conversion to a modified antitoxin which is capable of blocking the wheal and erythema reaction caused by injection of toxoid into sensitized skin. Heating at 56°C. does not result in an appreciable loss of neutralizing power as judged by tests in rabbit and human skin. The anaphylactogenic property of nonprecipitating antibody is likewise unaffected by heat at 56°C.

3. Precipitating antitoxin is incapable of sensitizing normal skin to toxin or toxoid and disappears rapidly from the injected sites. It fixes complement to high titer and sensitizes guinea pigs to fatal anaphylactic shock. It was possible to demonstrate inhibition of the wheal and erythema reaction in sensitized skin by injecting certain mixtures of precipitating antitoxin and toxoid.

4. The two antitoxic sera studied in greatest detail represented extreme cases. Many persons immunized with toxoid developed both precipitating and nonprecipitating antitoxin simultaneously.
THE EFFECT OF CORTISONE ON THE SHWARTZMAN REACTION
Authors: Thomas Lewis , Good Robert A. ,   With the Technical Assistance of Jay N. Little
Published: June 2004

1. Cortisone, in a dose of 25 mg. daily and with a pretreatment period of 3 days, in rabbits weighing 1 to 1.5 kilos, did not inhibit the dermal Shwartzman reaction produced by meningococcal or S. marcescens toxin.

2. In cortisone-treated rabbits, a single intradermal injection of toxin produced a primary reaction of hemorrhage and necrosis in the skin at the injected site. This lesion resembled the Shwartzman reaction in its gross and histological appearance.

3. Like the Shwartzman reaction, the primary hemorrhagic reaction in cortisone-treated rabbits was prevented by nitrogen mustard, and the preventive effect of nitrogen mustard was partly eliminated when the femoral marrow was protected against the latter agent.

4. A single intravenous injection of meningococcal or S. marcescens toxin, in cortisone-treated rabbits, was followed by bilateral cortical necrosis of the kidneys in the majority of instances. The renal lesions, as well as hemorrhages in the lungs, spleen, liver, and gastrointestinal tract, resembled the lesions of the generalized Shwartzman reaction. Histologically, the glomerular capillaries in both types appeared to be occluded by homogeneous, eosinophilic material which showed a strongly positive Schiff reaction.

5. The renal lesion following a single injection of toxin in cortisone-treated animals, and that following two intravenous injections in the generalized Shwartzman reaction, were both completely prevented by nitrogen mustard. This effect of nitrogen mustard was inhibited when the femoral marrow was protected against the latter agent.

6. The injection of S. marcescens toxin into the skin of normal rabbits did not cause systemic symptoms, nor was it possible to provoke the generalized Shwartzman reaction by this route. In cortisone-treated rabbits, a similar intradermal injection was regularly followed by the development of bilateral cortical necrosis of the kidneys, indicating that absorption of toxin from the skin occurred in these animals.

7. Possible mechanisms to account for the observations are discussed.

The authors are obliged to Professor James R. Dawson for many helpful suggestions during the course of this investigation.
AN ELECTROPHORETIC STUDY OF URINARY PROTEIN IN THE RAT
Authors: Sellers Alvin L. , Roberts Sidney , Rask Irene , Smith Stephen , Marmorston Jessie , Goodman Howard C.
Published: June 2004

The nature of the proteins present in the urine of the normal rat has been investigated by electrophoretic analysis and by fractional precipitation of these proteins by ammonium sulfate. Components similar to serum α- and ß-globulin constitute the major portion of the urinary protein in both male and female rats.

Following the intraperitoneal injection of renin, a massive proteinuria occurs. The proteins excreted are similar in proportion and electric mobility to those of normal rat serum.
THE ASSAY OF HYPERTENSIN FROM THE ARTERIAL BLOOD OF NORMOTENSIVE AND HYPERTENSIVE HUMAN BEINGS
Authors: Kahn Joseph R. , Skeggs Leonard T. , Shumway Norman P. , Wisenbaugh Paul E.
Published: June 2004

Hypertensin has been assayed in the blood of patients with normal blood pressure and in those with essential hypertension in both the benign and malignant phases.

250 ml. samples of arterial blood were obtained, chemically purified, and concentrated to a volume of 1 ml. These extracts were then assayed in anesthetized rats.

The concentrations of hypertensin in the blood of patients with the malignant phase of essential hypertension were found to be greatly increased. The concentrations of hypertensin found in patients with benign hypertension had a moderate degree of overlapping with those found in the normotensive group, but the mean concentration of hypertensin in the former group was twice that of the controls. Although these results are statistically significant, the amounts of hypertensin recovered in the benign group are so small that no conclusions can be drawn as to its effectiveness in producing vasoconstriction in these patients.
THE INTRACELLULAR DISTRIBUTION OF LANSING POLIOMYELITIS VIRUS IN THE CENTRAL NERVOUS SYSTEM OF INFECTED COTTON RATS
Authors: Schwerdt Carlton E. , Pardee Arthur B.
Published: June 2004

A procedure has been described for the centrifugal fractionation of the cellular particulate components of CNS tissue infected with poliomyelitis virus. A study of the distribution of infectivity among these components revealed that approximately four-fifths of the virus is found free in the submicroscopic particle fraction. The validity of the conclusion that the virus is located in this fraction of the intact neuron is discussed.
THE RELATION OF HERPES VIRUS TO HOST CELL MITOCHONDRIA
Authors: Ackermann W. Wilbur , Kurtz Hilda
Published: June 2004

The intracellular distribution of herpes virus in embryonic liver was investigated. 80 per cent of the virus was found in the cytoplasm in what appears to be a form uncombined with mitochondria or nuclei. A significant amount of the virus (16 per cent) was found bound to the mitochondria by an intimate attachment. Furthermore evidence was obtained that the mitochondria from liver tissue undergo a selective deterioration when infected with herpes virus. The concept is advanced that these organelles function in the development of virus.
COMPLEMENT-FIXING ANTIBODIES TO TYPE 2 (LANSING) POLIOMYELITIS VIRUS IN A NORMAL POPULATION OF A SUBTROPICAL AREA
Authors: Goldblum Natan , Melnick Joseph L.
Published: June 2004

Sera collected in 1950 from the native population in the vicinity of Cairo, Egypt, have been tested for complement-fixing antibodies to Type 2 (Lansing) poliomyelitis virus.

Complement-fixing antibodies are confined to the age of 1 to 9 years if a serum dilution of 1:4 is used in the test, or to the age of 1 to 4 years with a serum dilution of 1:16.

A comparison has been made of the findings obtained in this study with the results for neutralizing antibodies previously reported. Complement-fixing antibodies were found to be temporary in nature while neutralizing antibodies were maintained for long periods of time. On this basis, criteria for "recent," "old," or "no infection" in poliomyelitis have been established.

Sixteen of the children were bled again in 1952, 18 months after the first bleeding and both series of sera were compared in complement fixation and neutralization tests. All children who were negative in 1950 and who developed c-f antibodies by 1952, also developed neutralizing antibodies to a titer of more than 1:250 during the same period. Some children who failed to develop c-f antibodies, did develop neutralizing antibodies although of lower titer than found in children in whom c-f antibodies made their appearance.

These findings are discussed in the light of theories regarding the mode of acquisition of antibodies to poliomyelitis virus.
ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA
Authors: Nelson John B.
Published: June 2004

On four occasions a naturally occurring mouse leukemia, which was maintained by serial passage in weanlings of the Princeton strain, was superseded by a syndrome typical of acute hepatitis. Once initiated, the disease was regularly transmissible by the injection of liver suspensions of sick mice. It was also passed, though irregularly, by feeding such suspensions, and it also followed cannibalism.

The course of the disease after intraperitoneal injection of liver suspensions into normal weanlings was commonly less than 7 days and the mortality rate nearly 100 per cent.

Focal or diffuse necrosis of the liver was the only constant lesion at autopsy. On recovery, which occurred only in exceptional cases, cirrhosis was often found.

The primary source of the disease was undetermined. Latent carriage by healthy mice was not detectable on direct examination nor by the serial passage of suspensions of normal livers.
EXPERIMENTAL HYPERGLOBULINEMIA
Authors: Richter Goetz W.
Published: June 2004

It was shown, by means of salt fractionation procedures and electrophoresis that a marked and sustained hyperglobulinemia regularly resulted when sodium ribonucleate was injected subcutaneously at frequent intervals into rabbits undergoing immunization with horse serum. The hyperglobulinemia was characterized by a large increase in the gamma globulin levels, and a slight increase in the alpha and beta globulin levels. In control experiments done concurrently, the immunization of rabbits with horse serum, accompanied by subcutaneous injections of saline instead of ribonucleate, resulted in only moderate elevations in gamma globulin levels, while injections of ribonucleate alone brought about slight elevations in all three globulin components in some of the animals.

Precipitin tests showed that the rabbits immunized with horse serum and simultaneously treated with ribonucleate developed antibody titers against horse serum that were no higher than those of the immunized controls given saline instead of ribonucleate. Indeed, some of the animals treated with horse serum and ribonucleate had globulin levels that were much higher and had antibody titers that were significantly lower than were those of several rabbits receiving horse serum and saline. Injections of ribonucleate alone did not result in the formation of specific antibodies detectable by means of precipitin tests. The results made it plain that the hyperglobulinemia of the animals treated with horse serum and ribonucleate was not due to an excessive production of specific antibodies.

The findings as a whole provide further evidence that nucleotides play an important role in the formation of proteins in animals, and they indicate that an abnormally increased utilization of ribonucleotides by cells capable of producing globulins may be a causative factor in the pathogenesis of hyperglobulinemia.
STUDIES ON THE PROPAGATION IN VITRO OF POLIOMYELITIS VIRUSES
Authors: Scherer William F. , Syverton Jerome T.
Published: June 2004

The growth of poliomyelitis virus, Type 2, Yale-SK strain, in cultures of monkey testicular tissue was observed to occur in discrete cycles. Growth curves showed that each cycle was composed of (a) an initial lag phase when little or no virus was released from the cells, (6) a phase of viral production, and (c) a plateau which represented a decrement in the rate of viral production. This pattern of viral multiplication occurred in monkey testicular tissue cultures which have as the liquid phase either ox serum ultrafiltrate or monkey serum-chicken embryonic extract medium. The presence of a solid medium composed of chicken plasma, clotted either with chicken embryonic extract or bovine thrombin, did not alter the pattern of viral multiplication. The shape of the growth curve as established by any of four different techniques for tissue cultivation, was shown to be independent of the cultural technique employed.

For cultures of monkey testicular tissue, the amount of virus in the tissue was as much as tenfold greater than that in the liquid of the same cultures. Moreover, viral production was evident earlier and was detectable for a longer period of time in the tissue than in the liquid phase.

The rapidly incremental phase of the growth cycle, when large quantities of virus were released into the liquid phase, coincided in time with the destruction of the spindle-shaped cells, which extended from the explants. Although destruction of outgrowth cells was marked, there remained cells within the explants capable of supporting the growth of poliomyelitis virus.
ADAPTATION OF GROUP B COXSACKIE VIRUS TO ADULT MOUSE PANCREAS
Authors: Dalldorf Gilbert , Gifford Rebecca
Published: June 2004

An alteration of tissue tropism of a Coxsackie virus has been observed following different methods of propagation of the virus in animals.

Tropism for the adult mouse pancreas, as described by Pappenheimer, appeared to be irrevocably lost following prolonged brain-to-brain transfer.

It was present in the same strain on reisolation from human feces, was intensified following pancreas transfers, and suppressed by brain transfers.

Pancreatotropism may be correlated with the titer of virus in the pancreas.
STUDIES ON THE GENERALIZED SHWARTZMAN REACTION
Authors: Thomas Lewis , Good Robert A.
Published: June 2004

Certain factors involved in the production of the generalized Shwartzman reaction with meningococcal toxin in rabbits were investigated. The optimal amounts of toxin for the preparing and provoking injections, and the optimal time interval between injections were determined. Under suitable conditions of dosage and timing, bilateral cortical necrosis of the kidneys was produced in a high proportion of animals. When excessive amounts of toxin were used for preparation the incidence of the reaction was reduced.

Animals undergoing the generalized Shwartzman reaction became severely prostrated within several hours after the provoking injection of toxin. The renal lesion became fully developed within 24 hours, and its occurrence was associated with a rise of the blood non-protein nitrogen. Edema and petechial hemorrhages in the ears were observed in rabbits with advanced renal lesions.

The earliest change in the kidneys in the generalized Shwartzman reaction was the appearance of homogeneous, eosinophilic material, resembling fibrinoid, within the lumen of the glomerular capillaries. Occlusion of the capillaries by this material was regarded as the cause of subsequent tubular necrosis in the renal cortex. The material appeared to be derived from the blood, rather than from the capillary walls.

Cortisone enhanced the lethal effect of a single, large dose of meningococcal toxin, as well as causing bilateral renal cortical necrosis. The generalized Shwartzman reaction produced by two injections of toxin was aggravated by cortisone and ACTH.

Profound polymorphonuclear leukopenia was produced by both the preparing and provoking injections of toxin. When leukopenia was produced before the preparing injection of toxin, by treatment with nitrogen mustard, the generalized Shwartzman reaction was inhibited. During the intervals before and after leukopenia, and when leukopenia was prevented by shielding the femoral bone marrow from the action of nitrogen mustard, no inhibition of the generalized Shwartzman phenomenon was demonstrable.

Various colloidal and particulate materials, which are capable of provoking the local skin Shwartzman reaction when injected intravenously, failed to provoke the generalized Shwartzman reaction.

A working hypothesis was set up to account for certain events in the generalized Shwartzman reaction.
STUDIES ON THE MECHANISM OF EXPERIMENTAL PROTEINURIA
Authors: Sellers Alvin L. , Smith Stephen , Marmorston Jessie , Goodman Howard C.
Published: June 2004

When renin is administered intramuscularly to the rat, massive proteinuria occurs without a significant elevation of mean arterial blood pressure. The intravenous administration of renin to normal rats results in a great increase in urinary protein excretion. This response to renin is abolished by bilateral adrenalectomy. While the adrenalectomized rat fails to respond to intravenous renin with increased proteinuria, it does exhibit a normal elevation in mean arterial blood pressure. It is concluded that in the rat, the proteinuric property of renin is not related to the ability of this compound to elevate arterial blood pressure.

The passage of plasma proteins has been followed through the kidney and into the urine by attaching them to the dye T-1824 (Evan's blue). The intra-peritoneal injection of renin causes a massive, transient proteinuria in the rat. From a study of frozen sections of the kidney of rats whose plasma proteins are labelled with T-1824, it is concluded that the preponderant basis for renin proteinuria is an increase in glomerular permeability.
ANTIGEN RETENTION IN THE RABBIT
Authors: Stevens Kingsley M. ,   With the Technical Assistance of Raymond J. Lichter
Published: June 2004

Normal and irradiated rabbits were given small doses of I131 bovine gamma globulin (BGG) and the rates of its loss from their blood were determined. The figures agreed with those of previous reports.

3 to 4 months later, both groups were reinjected with antigen. The control group gave an accelerated (anamnestic) rate of loss, indicative of the immune state. The irradiated group gave a response similar to that given by the control group on primary injection.

Rabbits recover from 500 roentgens of x-ray in less than 2 months. Hence, rabbits given BGG soon after irradiation should become immune to this antigen in 2 months if they retain it. Since rabbits reinjected with BGG 3 to 4 months after irradiation did not give an accelerated response, the BGG must not have been retained over the period of time necessary for recovery; i.e., less than 2 months. As the rate of antigen loss is greater in normal than in irradiated animals, normal rabbits will have lost BGG as active antigen prior to the irradiated animals.

The amounts of antigen used (0.25 to 0.4 mg./kg.) more nearly approximate the amounts present during disease than have the amounts used in previous studies of antigen retention.

The hypothesis that protein antigens are lost as fast or faster than homologous proteins is discussed and the conclusion reached that this is a valid concept.
ON THE NATURE OF BACTEREMIA IN EXPERIMENTAL PNEUMOCOCCAL PNEUMONIA IN THE DOG
Authors: Gregg Lucien A. , Robertson O. H.
Published: June 2004

With the purpose of ascertaining the influence exerted by the pneumococcidal activity of the blood on the course of bacteremia occurring in experimental canine pneumococcal pneumonia, a study was made of the rates at which intravenously injected pneumococci disappeared from the circulation and the shed blood of diseased dogs. Preliminary studies on normal animals showed that blood containing hundreds of thousands of pneumococci per cc. immediately after injection usually became sterile or nearly so within an hour's time. Simultaneous observations carried out on the blood in vitro showed an analogous rapid disappearance of the microorganisms, although the effect was not quite as marked. Similar tests on non-bacteremic dogs with pneumonia revealed essentially the same ability of the body to dispose of large numbers of circulating pneumococci. The shed blood likewise exhibited marked bactericidal power.

The occurrence of bacteremia during pneumonia did not retard greatly the rate at which injected pneumococci disappeared from the circulation, as compared with the non-bacteremic state. After several hours the numbers of circulating microorganisms were approximately the same as prior to the intravenous injection. Blood in vitro often cleared as fully as it did in vivo over the same length of time.

Studies on the role played by humoral immune substances in the bactericidal action of the blood showed that while their presence was necessary for maximum killing power, and that bacteremic blood lacking humoral immune properties was rarely capable of self-sterilization in vitro, nevertheless such blood often retained considerable bactericidal potency as shown by its ability to reduce materially the numbers of pneumococci added to it. This phenomenon is discussed.

The marked pneumococcidal capacity of the blood exhibited by dogs with experimental pneumococcal pneumonia and its persistence during bacteremia suggest that this constitutes the principal mechanism for limiting the degree of blood invasion. The similarity of the findings in canine and human pneumococcal lobar pneumonia is pointed out.
SPERMINE OXIDASE: AN AMINE OXIDASE WITH SPECIFICITY FOR SPERMINE AND SPERMIDINE
Authors: Hirsch James G.
Published: June 2004

Sheep serum and bovine serum contain an enzyme which brings about a rapid oxidative deamination of certain biological amines. This enzyme differs from previously described amine oxidases in several regards and especially in its substrate specificity. Studies thus far indicate that only spermine and the closely related compound spermidine serve as substrates for the enzyme in sheep serum. For this reason, the enzyme has been named spermine oxidase.

Spermine oxidase is active in a variety of fluids of various ionic strength and buffer composition. The reaction takes place between pH 6.0 and pH 8.0 with an optimal rate in the vicinity of neutrality.

Under certain conditions, the rate of oxygen consumption during the initial phase of the reaction is independent of the concentration of substrate. The diminution in rate observed during the latter phase of the enzymatic attack appears to be due to an alteration in the kinetics at low concentrations of substrate, or to competitive inhibition by a product of the reaction.

Carbonyl reagents almost completely block the action of spermine oxidase, while certain amines and the cyanide ion bring about partial inhibition. Thiol reagents and sequestering compounds do not alter the course of the oxidative process. In the presence of low concentrations of mercuric chloride, the sheep serum-spermine system consumes approximately twice as much oxygen as controls containing no mercuric ion. The mechanism by which the mercuric ion stimulates additional oxygen uptake is obscure.
EFFECT OF THE COMPOSITION OF THE GASEOUS AND AQUEOUS ENVIRONMENTS ON THE SURVIVAL OF TUBERCLE BACILLI IN VITRO
Authors: Dubos René J.
Published: June 2004

Tubercle bacilli die much more rapidly under anaerobic than under aerobic conditions. Anaerobically, the rate of death is accelerated by increased CO2 pressure, and when certain metabolites (lactate for example) are present in the medium.

Death of the bacilli under certain conditions of anaerobiosis is accompanied by loss of ability to take the acid-fast stain and by progressive cellular disintegration.

These findings are discussed in relation to (a) the glycolytic equipment of tubercle bacilli, (b) their fate in tuberculous lesions.
QUANTITATIVE STUDIES OF THE VIRUS-HOST RELATIONSHIP IN CHIMPANZEES AFTER INAPPARENT INFECTION WITH COXSACKIE VIRUSES
Authors: Kraft Lisbeth M. , Melnick Joseph L.
Published: June 2004

Eight chimpanzees were fed and/or inoculated with a single Coxsackie (C) virus or combinations of different ones. The responses in terms of complement-fixing (c-f) antibodies to 6 to 10 such viruses were measured throughout periods of 1 to 2 years. Although the animals usually responded with rises in homologous antibodies after the feeding or the inoculation of viruses of special immunological types, a variable number of heterologous c-f antibodies were observed to increase significantly at the same time.

When immune animals were challenged with homologous virus, they failed to become virus carriers again and no rises in neutralizing antibodies were detected. However, the challenge usually resulted in a boost in the titer of the homologous c-f antibody and often of heterotypic c-f antibodies. This was particularly striking in those chimpanzees in which the c-f antibody had fallen below a detectable level.

In contrast to this, the infection of chimpanzees with agents outside the Coxsackie family (poliomyelitis viruses and Egyptian strains of West Nile virus) failed to influence the level of Coxsackie antibodies even during the periods when c-f antibodies to these non-Coxsackie viruses were rapidly rising.