bluuebunny/crossref_metadata_2025_split huggingface dataset:
A NEUROPATHOLOGICAL STUDY OF ACUTE HUMAN POLIO-MYELITIS WITH SPECIAL REFERENCE TO THE INITIAL LESION AND TO VARIOUS POTENTIAL PORTALS OF ENTRY
Authors: Faber Harold K. , Silverberg Rosalie J. 
Published: June 2004

The peripheral and central nervous tissues of eight patients dying of acute poliomyelitis were examined histologically to discover whether and to what extent the distribution of lesions was consistent with the hypothesis that virus enters the mucous membranes through the superficial nerve fibers, infects the neurons in peripheral ganglia, and proceeds thence into the central nervous system to infect connecting centers. Evidence consistent with this hypothesis was found in all cases. Based on concurrent lesions in the primary and secondary centers, the frequency of involvement of the various systems and the probability of their having acted as primary pathways for entering infection may be summarized as follows:—
(a) Trigeminal afferent system (V cranial): very frequent.
(b) Visceral afferent system (IX and X cranial): fairly common but less than V.
(c) Gustatory system (VII, IX, and X cranial): occasional.
(d) Sympathetic system, upper levels (pharynx, bronchial tree, upper esophagus): occasional.
(e) Sympathetic system, lower (intestine): occasional or doubtful.
(f) Vagal efferent (parasympathetic) system (X cranial) and olfactory (I cranial) system: uninvolved.
In general, the evidence of penetration through the upper alimentary and respiratory tracts was more conspicuous and consistent than through the lower alimentary tract. The pharynx appears to be an especially favorable site for the primary penetration of virus into the body.
Our data suggest that the primary lesion of poliomyelitis occurs in the peripheral ganglia.
Primary invasion through the sympathetics results in initial involvement of the central nervous system at the spinal level; invasion through all the other channels described results in initial involvement of the central nervous system at the level of the brainstem (midbrain, pons, medulla). In neither instance does the level of initial involvement necessarily determine the site of initial paralysis.
THE ACTIVATION OF SKIN GRAFTS
Authors: Rous Peyton 
Published: June 2004

Rabbit skin rendered hyperplastic by various agents showed less tendency than normal skin to contract when sliced off, and when used for grafts it united with the bed more rapidly and was vascularized sooner. The stimulated epidermis proliferated practically at once, and abundantly, to cover adjacent raw surfaces. Also the donor area healed much more swiftly than usual and became infected less often.
Certain grave limitations and hazards encountered during the experiments with hyperplastic grafts are considered.
FRACTIONATION OF MAMMALIAN LIVER CELLS BY DIFFERENTIAL CENTRIFUGATION
Authors: Claude Albert 
Published: June 2004

1. A method is described whereby the major components of liver suspensions are segregated according to size into three main fractions: (a) a large granule fraction composed of elements approximately 0.5 to 2 µ in diameter; (b) a microsome fraction composed of submicroscopic elements approximately 80 to 150 mµ in diameter; and, (c) a supernate fraction containing the soluble components of the extract.
2. The nature and origin of the constituents of liver extract is discussed. The large granule fraction is deemed to consist mostly of mitochondria and liver secretory granules, whereas the microsome fraction corresponds to the chromophilic ground substance of the hepatic cell. Phosphorus distribution in the supernate fraction, and ultraviolet absorption of the solution suggests that practically all the ribose nucleoproteins of liver extract are sedimentable, and occur in association with the large granules and microsomes.
3. The method of fractionation of liver suspension by differential centrifugation is being used as a means to investigate the chemical constitution of the morphological constituents of cytoplasm, and the distribution of biochemical activities in the cytoplasm of the hepatic cell.
4. The method of differential centrifugation is found to be applicable not only to the fractionation of cells but also, with the aid of auxiliary techniques, to the fractionation of much smaller elements, such as mitochondria.
THE PRODUCTION OF CHRONIC GLOMERULONEPHRITIS IN RATS BY THE INJECTION OF RABBIT ANTI-RAT-PLACENTA SERUM
Authors: Seegal Beatrice Carrier , Loeb Emily Nichols 
Published: June 2004

1. The injection of rabbit anti-rat-placenta serums in young adult rats produced chronic glomerulonephritis in 18 of 32 animals.
2. The course of the nephritis and the renal lesions were indistinguishable from those obtained in 11 of 13 animals injected with rabbit anti-rat-kidney serum.
3. Six instances of similar renal lesions occurred among 99 control animals. In 2 the rats had been injected with rabbit anti-rat-erythrocyte serum, in 2 with rabbit anti-rat-serum serum, while in 2 others the lesions were found among normal stock.
REACTIONS OF MONKEYS TO EXPERIMENTALLY INDUCED STREPTOCOCCUS HEMOLYTICUS, GROUP C, INFECTION
Authors: Saslaw Samuel , Wilson H. E. , Doan Charles A. , Woolpert O. C. , Schwab J. L. 
Published: June 2004

Macaca mulatta on a normal diet proved to be resistant on intranasal inoculation with Streptococcus hemolyticus, group C.
More than half of the monkeys maintained for various periods on a modified dietary regimen deficient in vitamin B became more or less anemic. All developed a granulopenic leucopenia during which many developed spontaneous infections, and all were extremely susceptible on intranasal instillation of Streptococcus hemolyticus, group C.
In normal monkeys, primary inoculation with the streptococcus resulted in an immediate marked neutrophilic leucocytosis. In the nutritionally deficient animals with leucopenia, only an abortive transitory leucocytosis was observed.
Following reinoculation with the same strain of hemolytic streptococci in normal healthy monkeys, the prompt leucocytic response originally observed, failed to develop, yet the animals remained asymptomatic. In the first instance the opsonic index remained low at the preinoculation base line level, but in the second, a sharp increase in the opsonic index occurred in several days. This humoral response apparently rendered unnecessary the quantitative granulocytic leucocytosis associated with survival in the first instance. There was no demonstrable difference in time of appearance or titer of the antibody responses, i.e. precipitins, antistreptolysins, and opsonins between the normal and nutritionally deficient monkeys.
Synthetic folic acid (L. casei factor) relieved both leucopenia and anemia promptly in the "vitamin M"-deficient monkeys, with increase in resistance to endogenous infection when this supplement was given sufficiently promptly.
STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMOCOCCAL PNEUMONIA
Authors: Wood W. Barry , Irons Edwin N. 
Published: June 2004

Experimental pneumococcal pneumonia was produced in albino rats by intrabronchial inoculation of Type I pneumococci suspended in mucin. The resulting pneumonia was uniformly fatal in untreated rats. Eighty per cent of the animals so infected and treated with sulfonamide drugs 6 hours after inoculation survived the pneumonia. At the end of 1 week the surviving animals were sacrificed, and examination of the lungs showed sharply demarcated localized pulmonary lesions containing no pneumococci.
Microscopic study of the lungs of treated animals sacrificed at 6, 18, 42, 66, 96, and 168 hours after the start of treatment revealed the following sequence of events. During the first 18 hours the drug apparently had little effect upon the pneumonic lesion, but at the end of 18 hours pneumococci in the edema zone began to show striking changes in their morphology, indicating bacteriostesis. Forty-two hours after the start of treatment the edema zone had disappeared, the pneumonia had ceased to spread, and the pneumococci at the margin of the lesion had been overtaken by leucocytes. Careful examination of the exudate in the periphery of the lesion revealed definite phagocytosis of pneumococci. By the 4th day no pneumococci could be found in the stained sections, and after 1 week there remained only macrophages in the rapidly clearing alveoli.
In order to demonstrate the phagocytic reaction more clearly the effect of sulfonamide drugs was studied in pneumonic rats previously rendered leucopenic by exposure to x-ray. The pneumonia in these animals was relatively acellular, and the few macrophages present in each alveolus could be seen to have phagocyted large numbers of pneumococci after 18 to 42 hours of treatment. The macrophages not only phagocyted the pneumococci but ultimately destroyed them, the pneumonic lesion later going on to complete resolution. The fact that this phagocytic reaction was observed in the lungs of animals with bacteremia suggests that the phagocytosis is independent of circulating type-specific opsonins.
THE PRESSURE AND INTERSTITIAL RESISTANCE PREVAILING IN THE NORMAL AND EDEMATOUS SKIN OF ANIMALS AND MAN
Authors: McMaster Philip D. 
Published: June 2004

Means have been described for the study of pressure conditions in normal and pathological skin of living human beings and mice. The true pressure in normal skin cannot be measured directly by any of the means hitherto described, because there is insufficient free fluid to make manometric determinations. However, for practical purposes, the intracutaneous pressure has been approximately estimated by introducing into skin exceedingly small amounts of a relatively unabsorbable fluid, a mixture of Locke's solution and a vital dye, and then finding the least pressure required to overcome the resistance of the skin to the passage of this fluid through it at the lowest rate measurable with accuracy by the apparatus at hand. In the present paper measurements of this pressure have been termed the interstitial resistance.
In normal skin the interstitial pressure, as estimated by measurements of the interstitial resistance, is low, slightly less, on the average, than 1.7 cm. of water in the skin of the mouse, and less than 3.1 cm. of water in human skin. It remains unchanged in states of active hyperemia.
In edematous skin the interstitial pressure can be directly measured by determination of the edema fluid pressure. It has been compared with determinations of the interstitial resistance and found to be only 0.5 cm. of water lower in both the mouse and man.
Under the conditions of our experiments, in skin rendered slowly edematous by the introduction of irritant chemicals or their topical application, little rise in pressure took place. On the other hand, in rapidly forming edema of the skin the edema fluid pressure and the intradermal interstitial resistance rose and became great enough to hinder materially the further escape of fluid from the blood vessels. The edema fluid pressure rose in proportion to the rapidity with which the edema formed. When a rapidly formed edema subsided, the edema fluid pressure and interstitial resistance fell, but if inflammation and induration followed later, the interstitial resistance became high again. As these conditions subsided the interstitial resistance fell, at times to normal levels, even in the presence of edema.
In mouse skin injured by squeezing according to a standard procedure, with result in pronounced edema, the intradermal interstitial resistance rose within a few hours to levels of 10 to 15 cm. of water. In those instances in which the injury progressed to induration, the interstitial resistance rose to such high levels that it seemed impossible that fluid could continue to escape from the capillaries. Such a state of affairs may be of great importance in determining whether necrosis follows trauma.
FLUORESCEIN CIRCULATION TIME AS A PROGNOSTIC SIGN IN EXPERIMENTAL TRAUMATIC SHOCK
Authors: Wang S. C. , Painter E. E. , Overman R. R. 
Published: June 2004

Repeated determinations of the circulation time by the fluorescein method were made in normal and shocked dogs. In normal animals the circulation time ranges from 9 to 16 seconds with an average of 12.6 seconds. In traumatic shock the circulation time is invariably prolonged.
For prognosis in the traumatized animal two determinations of fluorescein circulation time separated by an interval of 1 hour are essential. If the second circulation time is longer than the first and both are over 30 seconds, the animal will not survive without therapy. On the other hand, if the second circulation time is below 25 seconds or is considerably shorter than the first, the prognosis is good. In many of these experiments the change in circulation time appeared to be the earliest index of eventual recovery or death. It gave a clue to the fate of the animal when no decisive judgment could be made from the blood pressure and heart rate.
In three dogs the cyanide and fluorescein circulation times were compared during shock. It was found that the cyanide circulation time, though increased in shock, remained at a fairly constant value while over the same period the fluorescein circulation time showed progressive changes. This discrepancy between the cyanide and fluorescein methods may be explained by the fact that the former does not include the minute peripheral systemic circulation. Since the study of shock is concerned with tissue anoxia and is primarily a phenomenon of the failure of the peripheral circulation, it is important to choose procedures such as the fluorescein method as a measure of the condition of the peripheral vascular system.
THE VARYING BLOOD LEVELS AFFORDED BY PENICILLINS F, G, K, AND X IN RABBITS AND MAN
Authors: Eagle Harry ,   With the Technical Assistance of Arlyne D. Musselman
Published: June 2004

1. In both man and rabbit, penicillin X provided higher and more sustained blood levels than did penicillins F or G similarly administered in equal dosage (0.6 mg. per kg.); while penicillin K gave lower and evanescent levels.
(a) One hour after intramuscular injection, the blood levels in rabbits averaged 0.11, 0.18, 0.02, and 0.33 for F, G, K, and X, respectively; and levels of 0.1 mg. per kg. were sustained for 1, 1.4,0.5, and 2.1 hours, respectively.
(b) In man, the blood levels of G, K, and X averaged 0.23, 0.16, and 0.37 mg. per kg. 1 hour after intramuscular injections at 0.6 mg. per kg., and 0.11, 0.02, and 0.15 mg. per kg. 1 hour after intravenous injection.
(c) In man, a level of 0.1 microgram per cc. was sustained for 1.6, 1.2, and 2.3 hours after the intramuscular injection of G, K, and X, respectively, and for 1, 0.5, and 1.3 hours after their intravenous injection.
2. The total urinary recovery of penicillins F, G, and X varied between 68 and 100 per cent, averaging 61, 87, and 74 per cent, respectively, in rabbits. In man, the urinary recovery of G and X averaged 86 and 93 per cent, respectively. In sharp contrast, the urinary recovery of penicillin K averaged 33 per cent in seven rabbits and 28 per cent in six human volunteers. The major portion of the penicillin appeared in the first 30 to 60 minutes. This suggests a rapid inactivation of penicillin K in vivo.
3. The therapeutic significance of these data is discussed in the text, and in greater detail in the following paper.
THE THERAPEUTIC ACTIVITY OF PENICILLINS F, G, K, AND X IN EXPERIMENTAL INFECTIONS WITH PNEUMOCOCCUS TYPE I AND STREPTOCOCCUS PYOGENES
Authors: Eagle Harry ,   With the Technical Assistance of Arlyne D. Musselman
Published: June 2004

1. The relative bactericidal activities of penicillins F, G, K, and X against Type I pneumococcus in vitro were 60, 100, 180, and 135. The corresponding activities against Streptococcus pyogenes, strain C-203, were 75, 100, 115, and 145, respectively.
2. The total curative doses (CD50) of penicillins F, G, K, and X in pneumococcal infections of white mice (ten injections at 3 hour intervals) were 4.6, 3.8, 20, and 2.4 mg. per kg., respectively, or relative activities of 83, 100, 19, and 160, referred to G as 100.
3. The corresponding curative doses in streptococcal infections of white mice were 2.6, 1.3, 14.0, and 0.5 mg. per kg., or relative activities of 50, 100, 9, and 260.
4. Penicillin K was therefore one-tenth as active in vivo as would be implied by its bactericidal activity in vitro. This probably reflects its rapid inactivation in vivo, evidenced by the low and evanescent blood levels observed in both rabbits and man, and the low urinary recovery of this species of penicillin.
5. Penicillin X was significantly more active therapeutically than its bactericidal activity in vitro would imply. This probably reflects its slower inactivation in vivo, evidenced by the somewhat higher and more prolonged blood levels afforded by this penicillin in comparison with penicillin G. Judged by the mouse infections with the strains here used, penicillin X is the penicillin of choice in the treatment of infections with pneumococcus Type I and hemolytic streptococci.
6. The curative dose of penicillin in streptococcal and pneumococcal infections paralleled the varying susceptibility of these organisms to penicillin in vitro.
NORMAL STRUCTURE AND DEGENERATIVE CHANGES OF THE CYTOPLASM OF LIVER CELLS AND OF TUMOR CELLS DERIVED FROM THEM
Authors: Opie Eugene L. 
Published: June 2004

Discrete bodies which may be designated cytochondria occupy the greater part of the cytoplasm of liver cells. A part, but not all, of these bodies have the characteristics of mitochondria. They consist of a rim which stains deeply and a central part which stains faintly or remains unstained.
In liver cells about portal spaces, in foci of regeneration, and in tumor cells the rims of the cytochondria stain with basic dyes and contain ribonucleic acid or related substances.
With increasing accumulation of basophile substances about cytochondria as the central veins are approached, these bodies aggregate to form clumps or orient themselves with palisade-like arrangment in two rows just within the margins of the liver cell columns.
With aggregation of the cytochondria that are surrounded by basophile material, other cytochondria in the same cells are devoid of this material and wholly acidophile.
With chromatolysis (disappearance of basophile substance) caused by dimethylaminoazobeiizene (butter yellow) cytochondria lose their peripheral basophilia and stain only with acid dyes. When ribonucleic acid is removed from fixed liver tissue by ribonuclease, cytochondria lose their affinity for basic stains and become acidophile.
Of the cytochondria that are surrounded by ribonucleic acid or related substances part have the characteristics of mitochondria.
Under the influence of butter yellow cytochondria may become greatly swollen and intensely acidophile in the center though they retain their basophile rim. These swollen bodies in part at least have the reactions of mitochondria.
In tumor cells of hepatomas mitochondria are smaller and less abundant than in parenchymatous cells of the liver, and accompanying them are bodies of similar size which do not react as mitochondria.
The cytochondria of hepatomas produced by butter yellow undergo acidophile degeneration similar to that of liver cells and form swollen spherical bodies with basophile rims. With partial or complete loss of basophile substance, these altered cytochondria may form conspicuous cell inclusions.
AN EPIDEMIC DIARRHEAL DISEASE OF SUCKLING MICE
Authors: Pappenheimer Alwin M. , Enders John F. 
Published: June 2004

Intranuclear inclusions were found in 75 per cent of young mice suffering from a spontaneous diarrheal disease. They were confined to the epithelial cells of the small intestine, and to the intestinal and mesenteric lymphadenoid tissue. They were seen only between the 10th and 15th days after birth, in apparently healthy control mice of the same age group, they were found in only two of thirty-six animals (5.5 per cent) and these were in mice from the same room and stock as the diseased animals.
Nursing mice experimentally infected by feeding unfiltered diarrheal feces, also showed inclusion bodies from the 10th to the 14th day inclusive. The inclusions were not present during a corresponding age period, in the healthy stock used for these experiments.
Inclusions have also been found in the cytoplasm of the intestinal epithelial cells of young mice but without any significant relation to the disease under study. No conclusions as to their nature are warranted at this time.
RELATION OF THE SIZE OF THE INOCULUM AND THE AGE OF THE INFECTION TO THE CURATIVE DOSE OF PENICILLIN IN EXPERIMENTAL SYPHILIS, WITH PARTICULAR REFERENCE TO THE FEASIBILITY OF ITS PROPHYLACTIC USE
Authors: Eagle Harry , Magnuson H. J. , Fleischman Ralph 
Published: June 2004

1. A relatively small amount of penicillin sufficed to abort syphilitic infection in rabbits when administered during the incubation period of the disease.
2. The abortive dose, given as a single intramuscular injection in oil and beeswax, varied with the age of the infection.
(a) With a fixed intratesticular inoculum, the amount of penicillin necessary to prevent infection in half the animals remained at a constant level for 4 days. By the end of the 2nd week more than seven times this dosage was needed; and by the 6th week, after the chancre had appeared, more than thirty times the amount was needed to obtain the same result. The progressive increase in the abortive dose of penicillin with the passage of time probably reflects the interim multiplication of organisms.
(b) Qualitatively similar results were obtained in rabbits inoculated intracutaneously.
3. The abortive dose varied also with the size of the inoculum. In animals inoculated intracutaneously with 20, 2,000, and 200,000 spirochetes, and treated 4 days later, it required 200, 500, and 3,500 units per kg., respectively, to protect half the animals, and the corresponding PD90 dosages were 500, 2,000, and 16,000 units per kg.
4. The present observations, indicating the ease of aborting experimental rabbit syphilis during the incubation period by a single injection of penicillin, are perhaps applicable to the prevention of the disease in man.
5. Asymptomatic infections were rare in animals receiving inadequate doses of penicillin during the incubation period. Sixty-four of sixty-five such animals developed darkfield-positive lesions at the inoculated site. In animals treated 6 weeks after inoculation, however, after the development of lesions, inadequate treatment was usually manifested by an asymptomatic redissemination of organisms demonstrable only by lymph node transfer. The difference in the two groups probably reflects the beginning development of immunity in the rabbits treated 6 weeks after inoculation.
6. As suggested by Rake and Dunham (11), the treatment of animals during the incubation period permits a rapid assay of antisyphilitic agents, and one which requires only small amounts of material. Possible limitations of the method are discussed in the text.