THE ERYTHROPOIETIC ACTION OF GERMANIUM DIOXIDE

Injections were made of a sterile 0.4 per cent solution of germanium dioxide into four lots of mature male and female albino rats. Exact conditions of control were maintained. To two lots there was administered in four doses at intervals of 4 days a total of 6.6 mg. of the oxide per kilo of body weight. To two lots there was given in three doses at like intervals a total of 45 mg. of the compound per kilo of body weight. In each lot there was one rat which served as a control and which did not receive any germanium. A preliminary period of observation was maintained as a further control during which two determinations of the erythrocyte and leucocyte counts of the blood were made 7 days apart on all the rats. Weekly counts were made on all the rats during the progress of the investigation which lasted for 4 weeks, during 3 of which the treated animals were under the influence of germanium. In the first group 11 days elapsed between the last injection and the last count. In the second group the interval was 14 days. It was found that without exception all of the test rats responded to the germanium dioxide by a marked and sustained rise in the number of erythrocytes in the blood which ranged from 1 to nearly 5 millions. These results are statistically valid. There was an apparent tendency for the degree of effect to be related to the initial erythrocyte number, in that with a lower initial count there seemed to take place a greater rise, and vice versa. There was no indication that the larger doses of germanium dioxide exerted a greater stimulating effect on the production of the resultant erythrocythemia than the smaller doses. There is evidence that the effect is quick in making its appearance. The rise in the red cell count was found to occur within a week, and after but two injections of the oxide. Indications were obtained that germanium dioxide tends to increase the coagulability of the blood. Autopsy findings showed color changes in the liver and bone marrow. We believe that germanium dioxide is an erythrocytogenic agent and we hope that fruitful results will come from its therapeutic application.     

INFECTIOUS CATARRH OF THE ALBINO RAT : II. THE CAUSAL RELATION OF COCCOBACILLIFORM BODIES

Evidence is presented that infectious catarrh of the rat is caused by Gram-negative coccobacilliform bodies which resemble the agents of fowl coryza and mouse catarrh. These bodies were demonstrable microscopically in at least 90 per cent of the exudates from the nasal passages and middle ears. The characteristic syndrome was reproduced in selected rats by the nasal instillation of pure tissue culture growths and was maintained for 10 successive passages by the injection of exudate. The experimentally produced disease was also communicable by direct contact. The biological characteristics of the specific bodies are discussed in relation to the organisms of the pleuropneumonia group.     

STUDIES ON ENDEMIC PNEUMONIA OF THE ALBINO RAT : II. THE NATURE OF THE CAUSAL AGENT IN EXPERIMENTALLY INFECTED MICE

Coccobacilliform bodies, pleuropneumonia-like organisms, or other cultivable pathogenic bacteria were not demonstrable in lung and exudate suspensions from selected adult rats naturally infected with endemic pneumonia or from experimentally infected mice. The specific factor in lung suspensions from mice was identified with an agent which was active on dilution through 10⁷. It failed to pass through Berkefeld N filters but was generally present in V filtrates, with a loss in titer up to 1000-fold. It was largely removed from suspension on centrifugation at a speed of 9000 R.P.M. for 30 minutes. Attempts to cultivate the agent in embryonated eggs were uniformly unsuccessful. In fluid suspension it failed to withstand storage at 40°C. for a week but remained viable for at least 3 months in a frozen state under dry ice. The relation of the infective agent to viruses and to pleuropneumonia-like organisms is discussed.     

FURTHER STUDIES ON T. LEWISI INFECTION IN ALBINO RATS : I. THE EFFECT OF SPLENECTOMY ON T. LEWISI INFECTION IN ALBINO RATS AND THE PROTECTIVE ACTION OF SPLENIC AUTOTRANSPLANTS II. THE EFFECT OF THYMECTOMY AND BILATERAL GONADECTOMY ON T. LEWISI INFECTION IN ALBINO RATS

T. lewisi infection in normal adult 3 month old albino rats raised from a single stock and maintained under identical conditions was studied. Daily quantitative estimates of the trypanosomes in the circulating blood were made and the course of the infection was studied. Bilateral suprarenalectomy in rats lowers the resistance to a subsequent infection with T. lewisi. About 70 per cent of these rats die in an average period of 5.8 days after injection. The multiplication of the parasites, in the circulating stream, however, is not more considerable in the suprarenalectomized than in the previously normal rats, nor is the duration of the disease in the surviving rats any longer than in the normal group. The removal of the suprarenal glands does not alter the immune reaction to the parasite, but lowers the natural resistance of the animal to the toxic effects of the protozoan infection. Bilateral suprarenalectomy does not lessen the immunity of rats recovered from T. lewisi infection to subsequent infection. Unilateral nephrectomy does not influence the course of a subsequent infection with T. lewisi infection. The mortality of splenectomized rats from Bartonella muris anemia increases from 30 to 100 per cent following the injection of T. lewisi at the height of the anemia 7 days after splenectomy. T. lewisi infection 48 days after splenectomy that is to say at a time when the Bartonella anemia is no longer present produces a more severe infection than in normal rats. The number of trypanosomes at the height of infection averages 3 times the ordinary and the infection endures twice as long. Both the immune substance that inhibits the reproduction of the parasite and the lytic factor are markedly depressed. Splenic autotransplantation performed 4 weeks prior to splenectomy raises the resistance of rats to a subsequent T. lewisi infection. Thymectomy in 6 week old rats diminishes the severity of a subsequent trypanosome infection and shortens its course. Both the formation of the immune substance which inhibits reproduction of the trypanosomes and formation of trypanolytic antibodies are stimulated by this procedure. In the adult rat thymectomy shortens the course of the infection but the severity is only slightly diminished. Bilateral gonadectomy in the adult increases the severity of the infection. The number of trypanosomes at the height of the infection is almost three times the normal. However, the duration of the infection is the same as in the normal rats. The reproduction-inhibiting factor is depressed by bilateral gonadectomy but not the trypanocidal factor. Unilateral gonadectomy does not influence the infection.     

STUDIES ON ENDEMIC PNEUMONIA OF THE ALBINO RAT : III. CARRIAGE OF THE VIRUS-LIKE AGENT BY YOUNG RATS AND IN RELATION TO SUSCEPTIBILITY

An attempt was made to reestablish the virus-like agent associated with rat pneumonia by the nasal instillation of the infectious material into supposedly normal young rats from the selected Princeton colony. The incidence of the pneumonia in these animals after the injection of suspensions of pneumonic lungs from either rats or mice was not significantly greater than the incidence under natural conditions. In attempting to account for the refractory state of the immature rats it was found that the agent was widely dispersed through the breeding colony at an early age. Detailed tests of many litters indicated that the agent was acquired shortly after birth by way of the upper air passages as the result of maternal contact. In most instances it was so well tolerated by young rats during the suckling period and for several months thereafter that its presence was recognized only by nasal transfer to mice. There is every indication that the rate of infection of rats in the breeding colony approaches 100 per cent by the time the animals are old enough to be used experimentally.     

A PYOGENIC FILTERABLE AGENT IN THE ALBINO RAT

A filterable agent resembling the viruses is described. It was encountered in sarcoma 39, a propagable neoplasm of the white rat, and has now been maintained in this species for 28 passages over a period of some 7 months without appreciable loss in virulence. Its chief effect is the production of large abscesses in an animal species comparatively resistant both to viral diseases and suppuration. The white mouse is more susceptible than the white rat, the rabbit less so, and the guinea pig highly resistant. The agent has been repeatedly recovered from sarcoma 39 treated in special ways, but under the ordinary circumstances of routine transplantation it does not manifest itself. As yet there is no certainty on where it came from or how it maintains itself under natural conditions.     

MEDIATORS OF INFLAMMATION IN LEUKOCYTE LYSOSOMES : II. MECHANISM OF ACTION OF LYSOSOMAL CATIONIC PROTEIN UPON VASCULAR PERMEABILITY IN THE RAT

The vascular permeability-increasing action of rabbit PMNL lysosomes has been studied in skin and cremaster muscle of the rat. Both an extract of frozen-thawed granules and a cathepsin-free cationic protein fraction of the granules (which had previously been demonstrated to cause leukocyte adhesion and emigration in vivo) induce increased vascular permeability in skin and muscle which resembles that produced by histamine or histamine-liberators with respect to the timing of the response and the predominant type of microvessel affected. Extracts of frozen-thawed lysosomes and the inflammatory lysosomal cationic protein both cause disruption of rat mesenteric mast cells in vitro, whereas a granule-free cytoplasmic fraction of PMN leukocytes and a non-inflammatory cationic protein fraction of the granules do not do so under identical test conditions. The mastocytolytic action of lysosomal materials in vitro is not inhibited in the presence of 10 kallikrein-inhibiting units of trasylol per ml. The mast cell rupturing fraction of PMNL granules (cationic protein) possesses no detectable peroxidase activity or acid-mucopolysaccharase activity. When compared with compound 48/80 on the basis of estimated molecular weight, the lysosomal cationic protein appears to be at least as active as the latter compound with respect to in vitro mastocytolytic potency. Chronic pretreatment of rats with an agent known to reduce tissue mast cell numbers causes marked suppression of the vascular permeability change normally induced in skin and muscle by lysosomal extracts and cationic protein. Similar results are obtained if lysosomal materials are tested in rats pretreated with an antihistaminic. These observations are discussed with respect to the mode of action of PMNL lysosomes in the early and late phases of local tissue-injury reactions.     

THE PROTECTIVE ACTION OF COPPER AGAINST TRYPANOSOMA EQUIPERDUM INFECTION IN ALBINO RATS

The effect was studied of additions of copper to an adequate diet on the course of infection with Trypanosoma equiperdum in rats. Copper in amounts equivalent to 0.2 mg. of elemental copper per rat per day during a period of 10 days prior to an induced infection with small numbers of trypanosomes raised the natural resistance of the rat to the infection. The infection was aborted in all instances when the rats were infected by the injection of 2,000 trypanosomes and in 75 per cent of instances when the rats were infected by the injection of 10,000 trypanosomes.     

SEVERE ACTIVE CUTANEOUS HYPERSENSITIVITY IN THE RAT PRODUCED BY HEMOPHILUS PERTUSSIS VACCINE

Hemophilus pertussis vaccine injected into normal rat skin produced local edema lasting several days. Four to 6 days later the injected site became severely inflamed. When uninjected skin was challenged 5 to 28 days after the initial injection, severe inflammation developed at the site of challenge within 12 to 24 hours. This secondary hypersensitive response was elicited by a dose of vaccine which produced little or no initial or delayed inflammation in a normal rat. Specific cutaneous hypersensitivity to a particulate antigen (i.e. typhoid vaccine) or a soluble antigen (human or rabbit gamma globulin) developed when rats were injected with a mixture of the antigen and pertussis vaccine. Pertussis vaccine mixed with typhoid vaccine did not enhance circulating agglutinin formation to typhoid vaccine. Cutaneous hypersensitivity to pertussis vaccine was passively transferred to normal rats by lymph node cells but not with serum from hypersensitive rats. Sensitization with pertussis vaccine did not enhance the edema-producing activity of histamine, serotonin, or 48/80 given subcutaneously. Mast cells in areas of hypersensitive inflammation were not damaged appreciably. The hypersensitive inflammation was not inhibited by treatment with anti-serotonin and antihistaminic drugs. Hypersensitive rats "depleted of mast cells" responded to challenge with pertussis vaccine with severe inflammation though their response to 48/80 was depressed. Hypersensitive rats treated with x-irradiation showed decreased hypersensitive inflammation though they responded normally to 48/80 and histamine. These studies failed to demonstrate a role for circulating antibody in the cutaneous hypersensitive inflammation produced in the rat by pertussis vaccine. Furthermore, the findings indicated that the cutaneous hypersensitive inflammation is not mediated by tissue serotonin and/or histamine.     

THE ETIOLOGY OF BARTONELLA MURIS ANEMIA OF THE ALBINO RAT : THE ISOLATION OF BARTONELLA MURIS

1. Bartonella muris has been isolated in pure culture on Noguchi''s leptospira medium from the blood of the splenectomized adult rat suffering with Bartonella muris anemia. 2. Bartonella muris is a small, actively motile, Gram-negative bacillus. It grows best on media containing blood and on Noguchi''s leptospira medium. The optimal temperature for growth is 20–25°C. It produces neither gas nor acid on media containing sugars. It does not hemolyze blood in artificial media. Viability of the cultures in leptospira media was maintained for 36 days. 3. With this culture a severe anemia was produced in rats weighing 30 gm., with the occasional appearance of Bartonella muris bodies on the red cells. The anemia occurred within 24 hours, and lasted for 3 to 5 days with recovery of the rat. Bartonella muris was recovered in pure culture from the blood of these animals. The blood of these rats was infectious for other 30 gm. rats. 4. 3 week old rabbits were infected with cultures of Bartonella muris, a severe anemia resulting after an incubation period of 48 hours. The organism was recovered from the blood on the 5th day after injection. Bartonella muris is non-pathogenic for adult rabbits. 5. A severe anemia was produced in young guinea pigs with cultures of Bartonella muris within 48 hours. The organism was recovered on the 2nd and 5th days after injection. Postmortem examination revealed changes in the organs similar to those found in splenectomized rats suffering with spontaneous Bartonella muris anemia. 6. The infection was reproduced in white mice. In one instance a severe anemia developed on the 5th and 6th days. The organism was recovered on the 6th day. 7. The anemia was produced in splenectomized adult rats of non-carrier stock. The organism was recovered from the blood stream of these rats. A marked leukocytosis was noted (65,000) at the peak of the anemia as is found in the spontaneous disease in infected splenectomized adult rats. 8. Serological tests have thus far failed to demonstrate the production of agglutinins, though complement-fixing antibodies are present in homologous sera in low dilutions.     

EFFECT OF FEEDING THE PINEAL BODY UPON THE DEVELOPMENT OF THE ALBINO RAT

The pineal body of young calves was fed to albino rats beginning at the age of 3 weeks and extending over periods of from 3 to 6 weeks. Four litters of rats were used. Of these, fourteen rats were fed the pineal powder and ten were used as control subjects. Observations in regard to developmental changes and microscopic examination of the endocrine glands and reproductive organs were made. The pineal-fed rats of the first two litters remained somewhat smaller than their controls. The pineal-fed and control animals of Litters 3 and 4 showed no differences in development. Microscopic studies showed no differences between pineal-fed and control rats. We may therefore conclude that feeding the desiccated pineal body of young calves to young albino rats fails to produce any effect upon the early development of these animals.     

NEPHROTOXIC SERUM NEPHRITIS IN RATS : II. PREPARATION AND CHARACTERIZATION OF A SOLUBLE PROTECTIVE FACTOR PRODUCED BY TRYPSIN DIGESTION OF RAT TISSUE HOMOGENATES

A soluble protective factor, capable of absorbing nephrotoxic antibodies from anti-rat kidney serum, can be obtained in high concentration by tryptic digestion of rat kidney homogenate. The factor is no longer antigenic or at most only slightly so. It is stable at 60°, destroyed by boiling, is non-dialyzable, can be precipitated by ammonium sulfate, but resists destruction by proteolytic and other enzymes. In accord with previous studies on the organ localization of the rat tissue antigen responsible for the production of nephrotoxic antibodies, the soluble protective factor, or antigen derivative, can be obtained by tryptic digestion of rat lung, skeletal muscle, heart, and liver.     

STUDIES IN FERMENT ACTION : II. THE EXTENT OF LEUCOCYTIC PROTEOLYSIS.

This work proves that the proteolytic action of leucocytes is not a simple cleavage by one ferment. There are present two proteases, one acting in an alkaline medium and the other in an acid medium. This confirms Opie''s work. In the leucocytes there was found in addition an ereptic ferment which is capable of acting in an acid or alkaline medium. Since this action is lost by heating to 70°C., and by drying and keeping the leucocytes, it probably represents a ferment which acts on the digestion products of the two proteases. Analogy with other ferments in the body confirms this opinion.     

VARICELLA IN MONKEYS : NUCLEAR INCLUSIONS PRODUCED BY VARICELLA VIRUS IN THE TESTICLES OF MONKEYS.

The eosin-staining nuclear inclusions found in the monkeys'' testicles inoculated with emulsified tissue of human chicken-pox lesions are specifically associated with the virus of varicella.     

FACTORS CONCERNED IN THE POLYCYTHEMIA PRODUCED BY THE SUBCUTANEOUS INJECTION OF EPINEPHRINE

The subcutaneous injection of epinephrine in doses of 1 mg. per kilo brings about a polycythemia, an increase in reticulocytes, and an increase in young forms of polymorphonuclear leucocytes. The polycythemia is no doubt in part a concentration phenomenon, but the presence of these young cells in increasing numbers is believed to be evidence that there is at the same time a discharge of cells from the blood-forming organs, due to the effect of the drug upon them. A similar effect is obtained by continued stimulation of the peripheral ends of the cut sciatic nerves in the curarized animal.     

发生器生产的二氧化氯对饮用水消毒效果及卫生安全评价

为评价二氧化氯发生器生产的二氧化氯对饮用水消毒效果及卫生安全性,采用悬液定量杀菌试验和动物试验对二氧化氢发生器工作1h后生产的二氧化氯消毒液进行消毒效果和毒性及消毒后水质理化指标的检测。结果,含1.0mg/L二氧化氯该消毒液作用3min,对水中大肠杆菌的杀灭率为100％;温度和浑浊度对杀菌效果的影响不明显;消毒后水的理化指标符合《生活饮用水卫生规范》的标准。毒理学实验结果显示,该二氧化氯消毒液口服对小鼠LD_(50)>10000mg/kg体重,属无毒级,弱蓄积毒性,对大鼠骨髓嗜多染红细胞无致微核作用。     

钙通道拮抗剂增强大鼠曲马多镇痛

目的：本实验旨在观察钙通道拮抗剂在与曲马多联合外周应用对大鼠的镇痛效应。方法：痛阈测定选用热板法。腹腔注射不同剂量的维拉帕米、曲马多或小剂量拉帕米和不同剂量曲马多联合注射。注药３０ｍｉｎ后痛阈。结果Ｌ曲马多单独应用时，镇痛效应确切，在所试剂量相关。维拉帕米单用时，无论剂量大小均无镇痛作用，但小剂与不同剂量曲马多联用，可显著增强曲马多的镇痛效应。预注受体阻断剂的试验表明：钙通道拮抗剂增强曲马多镇     

THE IMMUNITY PRODUCED BY THE GROWTH OF TETANUS BACILLI IN THE DIGESTIVE TRACT

1. A method for the production of tetanus by the injection of a fixed number of spores is described together with the tests made in selecting animals for experimental work. 2. Guinea pigs fed a single serological type of tetanus bacilli will, after 6 months, show considerable amounts of antitoxin in their sera and will manifest immunity to the type fed. To other types they are just as susceptible as are controls. 3. Animals fed several types are immunized to each of these types. It is pointed out in the discussion that the digestive tract of man may carry several types and that he probably reacts in a manner resembling the guinea pig carriers. 4. Guinea pigs that carry tetanus bacilli and have antitoxin in their sera show little if any resistance to tetanus toxin. 5. As there is no relation between the amount of antitoxin in the blood and immunity to tetanus we believe that other bodies, specific for type, must occur and make for the immunity observed.