ON THE PHYSICOCHEMICAL REGULATION OF THE GROWTH OF TISSUES : THE EFFECTS OF THE DILUTION OF THE MEDIUM ON THE GROWTH OF THE SPLEEN.

It may be concluded that the degree of dilution of the culture medium has a marked influence on the rate of growth of splenic tissue. The maximum acceleration was obtained in a medium composed of three volumes of normal plasma and two volumes of distilled water. The growth in this hypotonic plasma was very much larger than in normal plasma. On the contrary, the growth of the spleen in hypertonic plasma was always less than in normal plasma. In other experiments, we found that in diluted plasma there was also an acceleration of the growth of the skin, the heart, and the liver of chickens. The skin of adult frogs also grew more actively in this plasma. The optimum degree of dilution varied according to the nature of the tissues and to the species of the animals. While the plasma containing two fifths distilled water produced the largest growth of splenic tissue, a slightly less diluted medium was more favorable for the liver and the heart, and generally for the skin also. The action of hypertonic plasma varied also in a large measure. While the spleen did not grow at all in the medium containing 0.0124 and 0.0144 sodium chlorid, the skin, on the other hand, could stand a high concentration of the sodium chlorid. Even its growth was activated in media containing 0.0094 and 0.0124 sodium chlorid and was greater than with normal plasma. The spleen of kittens was very easily affected by the changes of the dilution of the plasma, while the skin of the frog presented its best growth in plasma containing one half distilled water. Marked variations in the sensitiveness of tissues to hypertonic and hypotonic media will probably be observed in animals of different species. From these experiments, three conclusions can be drawn: namely, that certain laws of growth, discovered by Loeb, in lower organisms are true also for higher organisms; that normal plasma is not the optimum medium for the growth of tissue; and that each tissue has probably its optimum medium. The growth of the spleen is, without doubt, considerably modified by the variations of the dilution and perhaps of the osmotic tension of the plasma. It is possible then that the influence of osmotic tension, discovered by Loeb, in the growth of certain organisms, is a general law applicable as well to higher forms of life— frogs, cats, and chickens—as to lower organisms—tubularia and sea-urchins. In placing tubularia in different dilutions of sea-water and distilled water, Loeb found that the greatest rate of regeneration was observed when two volumes of distilled water were added to three volumes of sea-water. But fertilized eggs of sea-urchins were more sensitive to the action of hypertonic plasma, and they all died in a dilution of sea-water with two fifths distilled water. If only one fifth distilled water was added to the sea-water they developed normally. We found that the cells of certain tissues of the chicken follow a similar rule, since the maximal growth of the spleen is obtained in plasma containing two fifths distilled water, while other tissues grow better in a less hypotonic medium. Normal plasma is certainly not the ideal medium for the growth of tissues, since slight modifications of the tension, the alkalinity, or the addition of certain inorganic salts to normal plasma, increase the rate of the growth of tissues.     

THE PATHOGENESIS OF THE HEMORRHAGIC DISEASES OF THE NEW-BORN

Those conditions of the new-born characterized by a hemorrhagic tendency, icterus, and fatty changes, are probably all syndromes which may occur as the result of a number of toxic agents. All of them, however, have been produced, in these experiments, by the action of a single experimental agent. Thus, a picture indistinguishable from that called Buhl''s disease has been obtained by the use of chloroform, as have also the pictures known as Winckel''s disease, melæna neonatorum, etc. Chloroform is not held to be the only substance that has this power. It stands rather as one member of a group of agents, the effects of which in general and in individual organs are similar to those caused by lack of oxygen. The essential features of these conditions have also been produced by direct asphyxiation of the fetus. The suggestion is therefore made that underlying all these symptoms and pathological complexes, there is a deficiency of oxidation, general, local, or selective, thus bringing this group of diseases into the general category of acute yellow atrophy of the liver, eclampsia, pernicious vomiting, cyclic vomiting, phosphorus poisoning, etc. In human beings, chloroform and asphyxia must, in many instances, be the determining causes. There remain, however, other cases in which different factors are to be sought.     

THE STRUCTURE AND DIFFERENTIATION OF THE SPECIFIC CELLULAR ELEMENTS OF THE PARS INTERMEDIA OF THE HYPOPHYSIS OF THE DOMESTIC PIG

The bearing of these results on the Herring-Cushing theory of pituitary secretion is apparent. For the first time a true secretion antecedent has been demonstrated in the cells of the pars intermedia, an antecedent which appears in the cells at the same period of development at which active pressor effects may be obtained from the gland extracts. The route of export of this material from the gland to its point of utilization, however, is unknown; it may go by way of the blood or, as required by the Herring theory, by the transneural route to the third ventricle. The objections to the latter conclusion have been amply expanded in the introduction to this paper, but here may be emphasized the fact that the fetal pig hypophysis contains no hyaline bodies. Indeed they are rare in the adult, though there may be seen in the cells of the pars nervosa in the processes of its intrinsic cells, granular deposits which we believe to be the antecedents of the hyaline bodies but which in the pig rarely are discharged and aggregated into discrete masses as in other mammals. The fact that some observers have obtained positive pressor effects from the nervous part of the posterior lobe, exclusive of the pars intermedia, need not weigh very heavily in attempting to trace the course of the secretion, when we reflect that the difficulties of making such a mechanical separation are almost insuperable, and that the chemical product of the pars intermedia is so soluble and vanishes from the cells so rapidly that it may well be diffusible through the thin membranes which intervene and penetrate post mortem into adjacent parts. We are inclined, therefore, to the view that the secretion leaves the gland by the vascular route rather than by way of the interfibrillar spaces of the pars nervosa.     

THE INDUCED SUSCEPTIBILITY OF THE GUINEA-PIG TO THE TOXIC ACTION OF THE BLOOD SERUM OF THE HORSE

Following the divisions before used, the results presented in the preceding pages may be briefly stated. I. The particular method of sensitization and the place where the test injection is made have an important bearing on the results obtained by various workers. Comparing the results obtained by the various methods, we may conclude that the incubation period of the hypersensitive reaction is not sharply limited, but that there is a progressive increase in sensitiveness from the sixth day, and presumably before that, extending over a period of several weeks. It seems very probable that the degree of hypersensitiveness attained where the sensitizing dose consists of a mixture of diphtheria toxin and serum is greater than when a single dose of the same small quantity of serum is given alone. II. Our early experiments, the first in this field, are in thorough agreement with those first reported by Otto, and shortly after him by Rosenau and Anderson. III. This hypersensitive reaction is transmissible from mother to offspring. The transmission is probably not equally effective in all cases, and individual young guinea-pigs probably vary greatly in the rate with which they lose their ability to react. As a result not all of the young of a hypersensitive mother react to a subcutaneous dose of five cubic centimeters of serum given when they are four or five weeks old. The reaction in the young animals differs quite markedly from that in those actively sensitized. These differences are such as to indicate that in the mother there is a considerable localization of the reaction in tissues and organs whose destruction does not cause sudden death. This local reaction is a protective factor and is not transmitted to the same degree as the factors involved in the fatal acute reaction. IV. The hypersensitive reaction to horse serum depends on the development of a special anti-body during the incubation period, which anti-body may be passively transferred to a fresh animal. If the dose of hypersensitive serum be sufficient, and the intoxicating injection be given directly into the circulation, this passive hypersensitiveness may be enough so that the animal will die when tested. There is also in the serum of hypersensitive guinea-pigs an uneliminated horse serum element or "rest," which is distinct from this antibody, and probably without influence on the course of the acute reaction. V. The anti-body on which the hypersensitive reaction depends may be entirely neutralized by horse serum without causing symptoms. The gradual introduction of increasing doses over a total period of twenty-four hours suffices for this. The animal is then, properly speaking, neither immune nor refractory, but is essentially in the condition of a normal animal which has recently had a large dose of horse serum. This rapid neutralization is made possible by the great binding power which the subcutaneous and other relatively unimportant tissues have for the toxic element of the serum. The so-called "Phenomenon of Arthus" is probably the same reaction for the rabbit that we have here dealt with in the guinea-pig. The fact that the manifestation is more prominently a local one depends on racial differences. I have encountered cases in the guinea-pig in which the conditions in the rabbit are closely simulated.     

THE VISCOSITY OF THE BLOOD OF THE DOG AFTER OBSTRUCTION OF THE UPPER GASTROINTESTINAL TRACT

Estimations of the viscosity of the whole blood and plasma of the dog after experimental upper gastrointestinal tract obstruction are reported. With cardiac obstruction there is a rapid and marked rise in the viscosity of the whole blood and some increase in the viscosity of the plasma. The changes after pyloric obstruction are similar to those observed after cardiac obstruction. After obstruction of the upper jejunum only slight changes are observed. The increase in viscosity parallels quite closely the degree of the toxemia. It is unaccompanied by any marked concentration of the blood.     

THE INFLUENCE OF THE ANTERIOR LOBE OF THE PITUITARY BODY UPON THE GROWTH OF CARCINOMATA

1. The administration of emulsions of the anterior lobe of the ox pituitary increases very markedly the rate of growth of the primary tumor in rats inoculated with carcinoma. The growth of small tumors is accelerated relatively more than that of large tumors. 2. This acceleration is only evidenced, however, at a certain stage in the growth of the tumor, subsequent to the twentieth day succeeding inoculation. The administrations do not enhance the tendency of the tumors to metastasize. 3. Liver emulsion does not cause an acceleration of the growth of carcinomata in rats.     

THE EXTENT OF THE CAPILLARY BED OF THE HEART

By means of injections made into the coronary arteries of beating hearts it has been possible to determine the number of capillaries in the normal heart muscle. This study has shown a very rich blood supply with an average of approximately one capillary for each muscle fibre in the ventricular walls and papillary muscles, and a less abundant supply in the auricular muscle and Purkinje system. The number of capillaries per sq. mm. of ventricular wall or papillary muscle is about twice that found by Krogh in skeletal muscle. Capillaries were not found constantly in the valves of hearts in which there was apparently a complete injection of the capillary bed. The method described for injecting the capillaries of the heart also provides a means of studying the blood supply to the muscle, valves and aortic wall in pathological hearts.     

学生健康体检结果分析

在校学生进行健康体检,对常见病患病率进行统计分析,提议在体检 中应加入血液流变学指标。     

THE INFLUENCE UPON THE SPLEEN AND THE THYROID OF THE COMPLETE REMOVAL OF THE EXTERNAL FUNCTION OF THE PANCREAS

The complete removal of the function of the pancreas concerned in digestion is followed by marked changes in the spleen and in the thyroid apparatus. Second, the spleen shows an extreme simple atrophy. Third, the thyroid apparatus exhibits a constant change shown by the macroscopic transparency of the gland, by the microscopic increase in the amount of colloid, by the chemical increase of the iodine content of the gland, and by the functional test of the delayed appearance of tetany after the complete removal of the thyroid apparatus.     

CHEMICAL CHANGES IN THE BLOOD OF THE DOG AFTER OBSTRUCTION OF THE ESOPHAGUS AND OF THE CARDIAC END OF THE STOMACH

Ligation of the cardiac end of the stomach or of the esophagus in ten dogs produced a severe toxemia, and rapid death. In seven of the animals there occurred a marked rise in the total non-protein nitrogen and urea nitrogen of the blood. The dogs living longest with cardiac obstruction showed a fall in blood chlorides and a rise in the CO²-combining power of the plasma. All the dogs with an obstruction of the esophagus showed a fall in blood chlorides. Control animals subjected to other types of abdominal operations showed no significant changes in the blood.     

THE EFFECT OF SODIUM CHLORIDE ON THE CHEMICAL CHANGES IN THE BLOOD OF THE DOG AFTER OBSTRUCTION OF THE CARDIAC END OF THE STOMACH

A study is reported of the effect of different methods of treatment on the toxemia of cardiac obstruction. The average duration of life of untreated dogs is 3 days. Three dogs treated with 1 per cent salt solution subcutaneously lived 32, 36, and 45 days respectively without developing a toxemia. 2 per cent glucose similarly given, does not alter the course of the toxemia. Concentrated salt solution in small quantities given directly into the jejunum prevents the marked rise in non-protein nitrogen but does not materially prolong life. Release of the obstruction does not change the course of the toxemia in untreated animals. The subcutaneous injection of 1 per cent sodium chloride solution after release of the obstruction causes a rapid return of the blood to normal and allows the animal to recover. A similar amount of fluid given as 2 per cent glucose does not alter the course of the toxemia after release of the obstruction.     

THE APPLICATION OF THE REACTION OF AGGLUTINATION TO THE PNEUMOCOCCUS

Owing to unavoidable circumstances only a limited amount of time was available for the work on agglutination. The foregoing report is therefore preliminary only and the following conclusions are provisionally offered: I. Pneumococci by reason of their agglutinating properties exhibit a tendency to separate into numerous groups similar to streptococci. II. Pneumococcus mucosus forms a distinct and consistent variety. The production by it of common agglutinins for some pneumococci and the resistance of the agglutinins produced by it to absorption by the streptococcus indicate a nearer relation to the former than to the latter organism. III. The agglutinating substances in the serum of immunized animals were demonstrated by absorption tests to consist of specific and group agglutinins in cases where the agglutinins were sufficiently developed to make use of this method. IV. The pneumococci seem to show marked differences in their ability to undergo agglutination. V. There was considerable uniformity of reaction of the various strains in low dilutions, but this uniformity is not continued as the animal becomes more highly immunized. VI. At present it is not possible to establish a definite relation between the agglutination reaction and the other characteristics of the pneumococcus excepting in the case of the Pneumococcus mucosus.