Normal Defense Research Articles

Effect of neonatal thymectomy on the induction of sarcomata in C57 BL mice.

MANY tumours induced in rodents by chemical carcinogens1 and by viruses2 are antigenic in animals of the same highly inbred strain and even in the primary autochthonous host3. It has, therefore, been suggested that an inadequacy of the immune system may be a factor in allowing the growth of an induced tumour. Much evidence has been obtained in favour of such a hypothesis. Newborn animals, which have an immature immunological system, are much more susceptible to the oncogenic effect of viruses4 and of minute doses of chemical carcinogens5 than are adult animals. Chemical carcinogens have been shown to interfere with the normal immunological defences of the host6. Thymectomy of neonatal mice7, rats8 and hamsters9 leads to some impairment of immunological function, particularly homograft reactivity, and renders animals more susceptible to the oncogenic effects of polyoma virus10 and 3,4-benzopyrene11. The experiments reported here were performed to test the oncogenic activity of another chemical carcinogen, 20-methylcholanthrene, in thymectomized mice. Inbred C57BL mice from the colony maintained at the Chester Beatty Research Institute were thymectomized or sham-thymectomized on the third day of life. At approximately five weeks of age 200 µg 20-methylcholanthrene (MC) in solution in 0.2 ml. tricaprylin was injected intramuscularly into the right thigh. The animals were examined weekly and sarcomata at the injection site were measured and recorded. Mice were killed once the sarcoma reached a size of 18–20 mm diameter, examined post mortem, and material was taken for histological investigation. The results are summarized in Table 1. Thymectomized mice were examined macroscopically and microscopically for thymus remnants, but the four mice in which these were found are not included in the table. All animals, except one sham-thymectomized mouse, developed sarcomata at the injection site.

ANTIMETABOLITE THERAPY IN MIDLINE LETHAL GRANULOMA.

During the past decade several authors^1,6have reviewed the scientific literature pertaining to midline lethal granuloma, and their efforts have culminated in a detailed description of the characteristic clinical picture and in an extensive evaluation of the available therapeutic modalities. While the etiology of midline lethal granuloma continues to remain a mystery, there is an increased tendency to regard this dread malady as a collagen disease related to periarteritis nodosa.^16,21The location of the major clinical manifestation strongly supports such a hypothesis, for the structures near the median line of the face are supplied by a rich network of smaller blood vessels. A breakdown in the normal defense mechanism of these tissues results in the formation of a granuloma whereas involvement of larger blood vessels leads to extensive destruction and necrosis. Recent experiments by Hans Selye¹⁷focus additional light on the development of allergic phenomena. Without

THERMAL STRESS AND INTERRENAL TISSUE IN THE PERCH PERCA FLUVIATILIS (LINNAEUS)

Experiments indicate 30–31°C as the upper thermal limit for perch since, irrespective of the level of their temperature acclimatization, they cannot survive hotter conditions for more than a few hours. Perch that were gradually heated in lethal temperature tests indulged in agitated exploratory behaviour as they neared their lethal levels of temperature. Just below the lethal, balance and coordination became seriously impaired, and the final phases of activity were marked by violent and disoriented swimming.Among other changes, atrophy of the interrenal tissue accompanied exposure to various levels of temperature. These changes were related to severity of thermal stress, being most marked when high temperature was prolonged during acclimatization at 28–30°C, when hyperplasias could also occur, or when temperature was raised rapidly to exceed the animal's thermal tolerance in lethal tests. At moderately high temperatures it sometimes appeared that interrenal cell hypertrophy could take place. Changes in other tissues—viz. renal tubules, head kidney, liver, muscle—generally only occurred at the higher levels of prolonged exposure. While the changes varied in character between tissues all are considered essentially degenerative, and due to some kind of breakdown of the body's normal defences against stress.To test the postulated function of interrenal tissue in combating various forms of stress, perch were chilled, made anoxic, and placed in diluted sea water, as well as heated. These experiments, with others in which perch received mammalian ACTH (both to test its general histological effects and in an attempt to influence lethal temperature) indicate an important function for interrenal tissue in offsetting stress.It is tentatively suggested that the complex of histological changes observed considerably resembles that of the “General‐Adaptation‐Syndrome” of mammals, that most of the histological changes are due to either adaptive or maladaptive adjustments of the perch's organ systems or tissues, and that interrenal tissue occupies a similar functional position in the perch to that of adrenocortical tissue in mammals in opposing stress, including the stress of heat.

The usefulness of in vitro sensitivity tests in antibiotic therapy.

INTRODUCTION With the advent of antimicrobial agents twenty-five years ago, the course of many infections has been profoundly altered since these agents have often enabled the normal defense mechanism of the body to be by­ passed. However, the enthusiasm and widespread use that followed the introduction of each new drug was gradually tempered by the knowledge that these drugs, by virtue of their ability to influence the host-parasite relationship, could exert harmful as well as beneficial effects. Further, it became obvious that certain criteria were required for the intelligent use of these antimicrobial agents. The rational use of antibacterial drugs should be based upon two prin­ ciples. First, the specific identity of the infecting organism must be de­ termined. Second, a test must be devised which will provide an accurate estimate that the antibiotic will be effective in vivo. An obvious solution to the latter problem is to assess the activity of a drug in experimental infec­ tions in animals. However, the response of these infections to antibiotics has been a notoriously unreliable guide to the treatment of human disease. In addition, this method is expensive, cumbersome, and does not lend itself readily LO use on a large scale. Therefore, efforts were channeled into the development of in vitro sensitivity tests and their application to clinical infections. One of the earliest methods attempting to apply in vitro tests to clinical situations involved comparison of the infecting organism with a standard strain of known susceptibility. This has been largely supplanted by tests based on a comparison of antibiotic concentration in body fluids with the minimal concentration of the drug necessary to inhibit growth of the organism in vitro. By definition, then, an organism is not considered sensitive unless the concentration of antibiotic attainable in the body ex­ ceeds that necessary to inhibit its growth in vitro (1). Several objections may be raised to this definition of sensitivity. First, local or humoral host defense mechanisms may act in synergism or antago-

The peritoneal fluid in strangulation obstruction: The role of the red blood cell and E. coli bacteria in producing toxicity

Summary An extensive investigation of the lethal properties of peritoneal fluid obtained from dogs dying of experimental strangulation obstruction of the small intestine has been carried out. Similar studies were also carried out on fluid obtained from a human with strangulation obstruction. The rat was used as a recipient animal, and the results obtained were then confirmed in the dog. It was found that the toxicity of strangulation fluid appears to be due to the presence of a hemoglobin concentration greater than 1 gm, per cent and a level of {ulE. coli} of 10 7 organisms per milliliter or higher. These findings were true of strangulation fluid from a human as well as strangulation fluid obtained from dogs. Furthermore, it was found posible to create a fluid of similar toxicity and physiologic action by growing {ulE. coli} in nutrient broth containing whole blood or saline washed red blood cells. The major portion of the toxicity of the red blood cell appears to reside in the soluble fraction of hemolyzed cells rather than in the red cell stroma. It is felt that a further understanding of the manner in which the red blood cell or its constituents interfere with the normal defense mechanisms in the peritoneal cavity may shed additional light on the problem of host resistance as a whole.

Influence of irradiation on resistance to infection.

Infection is a very frequent lethal complication of wholebody x radiation in the LD/sub 50/ to LDi/sub 100/ range of dosage. Normal defenses against infection depend upon several factors, including the polymorphonuclear leucocytes, antibodies, bactericidal power of serum, and the retictiloendothelial system. The effects of x-radiation damage on these mechanisms are discussed. The beneficial effect of spleen homogenates and spleen shielding and previous treatment with endotoxins in radiation induced infections are discussed. Possible reaction mechanisms involved are considered. 57 references. (C.H.)

INFLUENCE OF IRRADIATION ON RESISTANCE TO INFECTION

Infection is a very frequent lethal complication of wholebody x radiation in the LD/sub 50/ to LDi/sub 100/ range of dosage. Normal defenses against infection depend upon several factors, including the polymorphonuclear leucocytes, antibodies, bactericidal power of serum, and the retictiloendothelial system. The effects of x-radiation damage on these mechanisms are discussed. The beneficial effect of spleen homogenates and spleen shielding and previous treatment with endotoxins in radiation induced infections are discussed. Possible reaction mechanisms involved are considered. 57 references. (C.H.)

The Direct Plasmodicidal Effect of Quinine, Atabrine and Plasmochin on Plasmodium Lophurae

Journal Article The Direct Plasmodicidal Effect of Quinine, Atabrine and Plasmochin on Plasmodium Lophurae Get access R. I. Hewitt, R. I. Hewitt From the Health and Safety Department, Tennessee Valley Authority, and the Departments of Preventive Medicine and Pharmacology, University of Tennessee College of Medicine, Memphis Search for other works by this author on: Oxford Academic PubMed Google Scholar A. P. Richardson A. P. Richardson From the Health and Safety Department, Tennessee Valley Authority, and the Departments of Preventive Medicine and Pharmacology, University of Tennessee College of Medicine, Memphis Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 73, Issue 1, July 1943, Pages 1–11, https://doi.org/10.1093/infdis/73.1.1 Published: 01 July 1943 Article history Received: 28 December 1942 Published: 01 July 1943

The Development of Agglutinins for Aerobic, Gramnegative Bacilli in Patients with Diffuse Peritonitis or Abscess Formation Following Appendicitis

peritonitis and abscess formation. The bacteria most frequently isolated from these lesions are members of the B. coli group, certain streptococci, particularly of the enterococcus group, and sporulating anaerobic bacilli, such as B. welchii. It is only fair to assume that the outcome of these infections is directlydependent upon two factors, namely: (1) The virulence, invasiveness, and toxicity of the micro-organisms and (2) the normal and immune defence factors of the host. Because of the second factor, we undertook a study of the immune response of patients with diffuse peritonitis or abscess formation subsequent to perforated appendicitis. The results of this investigation on the development of agglutinins against aerobic, gram-negative bacilli in patients presenting these conditions, are reported in this communication.

Necrosis aguda del pancreas (pancreatitis edematosa y hemorragica).

The author has written an excellent monograph. The volume is 242 pages in length and has a fine bibliography. <h3>The following conclusions are drawn:</h3> Sixty per cent of human beings have a common duct of Wirsung, and the control of the sphincter of Oddi depends on the biliary duodenal reflux. The physiopathologic transformation produced by diseases of the biliary system and duodenum is caused by the failure of the normal defense mechanisms. In 60 per cent of the cases of acute pancreatitis abnormality exists in the biliary tract and duodenum. One is forced to admit the multiplicity of pathogenesis, since in many cases the disease takes a lymphovascular route, while in many cases there exists a concomitant hepatobiliary disease. One admits the existence of edematous pancreatitis of the following origins: idiopathic, lymphovascular, anaphylactic and inflammatory. The so-called edematous and hemorrhagic pancreatitis must be considered as part of the process

Non-Specific Factors in Resistance

Summary Reproducible correlation is demonstrated between ability to avoid common cold, in man, and ability to maintain that degree and type of capacity for response to the demands of effort and exposure which, in the rabbit, is indicative of maximal ability to resist invasion. The suggestion is made that the causal agent of common cold may be capable of precipitating onset most readily when available for invasion at a time when the normal defense against such invasion has been made transiently vulnerable as a result of fatigue-enforced increase in susceptibility to shock.

Natural Resistance and the Study of Normal Defence Mechanisms

Natural Resistance and the Study of Normal Defence Mechanisms

Natural Resistance and the Study of Normal Defence Mechanisms

Natural Resistance and the Study of Normal Defence Mechanisms

STUDIES UPON EXPERIMENTAL MEASLES

An active transmissible virus exists in the blood of measles patients during the eruptive stage of the disease. This virus produces in rabbits after intravenous injection a specific reaction analogous in all essential features to that of the human infection. Following a definite incubation period of from 2 to 5 days the animals infected show pyrexial, leucocytic, and cutaneous alterations. Fully 90 per cent of such inoculated rabbits react in a remarkable manner. The earliest constant symptom of the infection is a rise in temperature, which on the average occurs 4 days after inoculation and most probably marks the end of the incubation period. Concomitantly with this temperature rise there is a diminution in the total number of circulating leucocytes. This decrease in the number of white blood elements may be relative or may appear in the form of a well defined leucopenia. The most striking objective signs are the coryza, conjunctival injection, enanthemata, and exanthemata. The mucous membrane lesions are similar in their physical appearance to the so called Koplik spots seen in man. They occur on the buccal side of the oral cavity ranging in number from two to eight discrete hemorrhagic areas with paler centers. They appear as a rule coincidently with the temperature rise or shortly thereafter. The exanthematous lesions though occurring only in about 40 per cent of the infected animals complete the clinical syndrome in this particular experimental host. The rash may appear as early as the 3rd and as late as the 7th day after inoculation. In its early stage it is of the macular variety, appearing as a diffuse eruption which later develops into a more papular type of lesion. At this time the cutaneous manifestations appear as slightly raised, flattened, purplish red, discrete areas in the skin of the face, neck, chest, and abdomen. Repeated passage of the virus of measles through the rabbit seems to increase its virulence. A number of animals infected with such passage virus succumb in the fourth and subsequent generations, undoubtedly as the direct result of the action of the specific excitant, as in none of the animals was there cultural evidence of secondary intercurrent infection. In the animals dying presumably as a result of the specific virus grave nephritic changes were evident. It is a noteworthy fact that the pneumonia so common in fatal cases of human measles was not evident in any of the experimental animals. We believe this to be of considerable significance, especially in elucidating the direct etiological factor of the fatal pneumonias so often present in human measles cases. Apparently such infections in man can be explained purely on the basis of the destruction of normal defense barriers by the specific excitant of the infectious disease, and the lack of host resistance to the ordinary pyogenic microorganism.