Reduction in cellular tumorigenicity after mycoplasma infection and elimination of mycoplasma from infected cultures by passage in nude mice.
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Early stages of mycoplasma infection of mice and rats were accompanied by suppression of the populations of rosette- and plaque-forming cells. Later the character and dynamics of the immune response to M. arthritidis differed in mice and rats. In mice mycoplasma infection was accompanied by stimulation of rosette-forming cells with some suppression of the plaque-forming cells from the 7th to the 36th day of infection. In rats by the 7th day the number of plaque- and rosette-forming cells decreased in comparison with control, and the immune response was restored by the 15h day; at later periods the immune response of the infected rats exceeded the normal level considerably. The cellular and humoral immune reactions proved to depend on the mycoplasma dose.
Two hundred consecutive infertility patients and sixty-seven controls subjects were studied for the incidence of infection with Ureaplasma urealyticum (T-mycoplasma). On the basis of a complete infertility investigation, the infertility patients were subdivided into those with explained infertility and those with unexplained infertility. Of the patients with unexplained infertility, 55% had a positive culture for T-mycoplasma as compared with a 32% incidence of positive cultures in the control population. The differences were statistically significant. The 6-month pregnancy rate following successful antibiotic treatment in patients with unexplained infertility was 42%. The 6-month pregnancy rate in a comparable group of patients with unexplained infertility, seen during a 3-year period prior to mycoplasma culture and treatment, was 32%. The difference in pregnancy rates between the two groups was not statistically significant. No correlation was found between a poor postcoital test and the presence of T-mycoplasma infection nor between T-mycoplasma infection and poor cervical mucus. The role of T-mycoplasma infection in infertility was neither proven nor disproven by this study.
Attempts were made to isolate mycoplasmas from the uterine cervix of infertile women and normal pregnant and nonpregnant women to investigate the relationship of genital mycoplasma infection to infertility. Ureaplasma urealyticum was demonstrated in 63% of patients with infertility, 68% of normal pregnant women, and 62% of normal nonpregnant women. The incidence of Mycoplasma hominis infection was found to be noticeably lower, with corresponding isolation rates of 10%, 11%, and 6%, respectively. The differences in rate of isolation for U. urealyticum and for M. hominis among the three groups did not reach statistical significance. During a follow-up period of more than 12 months without any treatment for mycoplasma infection in the infertile cases, 11 women (27.5%) became pregnant. These included 7 (28%) of 25 women with positive U. urealyticum cultures. The results demonstrate a fairly high incidence of female genital infection with U. urealyticum which, as the data would indicate, cannot be directly associated with infertility.
Forty-two couples in an infertility clinic were examined for genital infection with Mycoplasma hominis or Ureaplasma urealyticum (T strains). In 21 couples one or other partner was found to be infected; no chlamydiae, trichomonads, or gonococci were isolated from any of these couples. All patients were then included in a double-blind crossover doxycycline/placebo study lasting 8 months. Pregnancy was achieved in one of the 21 couples who were free of infection. Of the 21 couples who were infected, one achieved a pregnancy while still infected, and 19 lost their infection on doxycycline, of whom four achieved a pregnancy. These four pregnancies all occurred among the 10 couples who received doxycycline first. One further pregnancy occurred after the trial was over. Since 5 of the 7 pregnancies occurred in the first 4 months of the trial, they were probably due to the psychological effect of treatment rather than the effect of the drug on infection.
Two children presented with an acute mycoplasma infection associated with a significant increase of antistreptolysin level. A severe nephropathy occurred, rapidly resulting in renal failure with histologic lesions of membrano-proliferative glomerulonephritis. Both patients had persisting low complement levels with low C3 and normal C4. The relationship between mycoplasma and streptococcal infections and the abnormality of complement and the renal disease is discussed.
Several rat tumor cell cultures were deliberately infected with three species of mycoplasma commonly found as contaminants of cell lines grown in vitro, and the effect of mycoplasma infection on the results of cytotoxicity assays was examined. Lymph node cells and spleen cells from normal animals showed an apparently high spontaneous cytotoxic activity against tumor cells infected with either M. arginini or M. hyorhinis, but the reactivity against cells infected with M. orale was not significantly higher than that against uninfected cells. The high reactivity towards tumor cells infected with M. arginini and M. hyorhinis bore a close resemblence to natural cell-mediated immunity in that spleen cells were much more reactive than lymph node cells, spleen cells from nude mice were as effective as spleen cells from normal mice, and the reaction crossed both strain and species barriers. However, closer examination revealed that the cytotoxic effects were directly caused by depletion of arginine or other essential nutrients from the medium. These findings imply that a cautious approach should be taken when interpreting certain aspects of spontaneous cell-mediated cytotoxicity, and that the greatest care be taken to ensure that the cells used as targets in any cytotoxicity test are mycoplasma-free.
Mycoplasma infection was present in the fetuses from three spontaneous abortions and in one second-trimester newborn. Gross examination revealed in most cases a severely infected placenta and membranes, with a fetus of normal appearance. The fetal infection presumably followed placental involvement and appeared to have been acquired shortly prior to delivery. Genital mycoplasmas, Ureaplasma urealyticum or Mycoplasma hominis, were isolated from the placentas and the fetal tissues, and from the genital tracts of the mothers. Isolation of mycoplasmas from the liver indicated that bloodstream dissemination of these organisms occurred in the fetus. In the fetus, the pathologic changes were variable. Lesions were identified in the lung by scanning electron microscopy of the bronchial tree in two cases and were accompanied by interstitial pneumonia. An abnormally dilated left ventricle suggestive of cardiomyopathy was observed in one case.
The effectiveness of counterimmunoelectrophoresis (CIEP) for detecting human precipitating antibodies to mcyoplasma antigen was compared with the conventional complement fixation (CF) method in a double-blind experiment. Fifty-one sera from patients suspected of having acute mycoplasma infection were tested by both techniques. Dense precipitin lines to mycoplasma antigen developed in 28 sera with CIEP. Twenty-six of 28 had elevated CF titers to this antigen. No precipitin bands were observed in sera with low antibody titers to mycoplasma. These findings indicate that the CIEP test is a specific method for reliably detecting elevated serum CF antibody levels in patients with acute or recent mycoplasma infection.
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Over a period of 16 months acute mycoplasma pneumonia was diagnosed in 20 patients. All were rapidly and completely cured by ampicillin and cephalosporins, which are ineffective against mycoplasma, indicating that acute mycoplasma infection in children does not require selective treatment, the pneumonia probably being caused by other micro-organisms. There is no prove that mycoplasma pneumonia heals spontaneously, without any therapy.
The controversy regarding the possible role of genital mycoplasma infection in human reproductive failure gave rise to a study in which pregnant rats, previously shown to be of normal fertility, were inoculated 7-11 days after conception with either Mycoplasma arthritidis or an equal volume of sterile broth medium. Repeated observations during the course of pregnancy revealed several pathogenic effects. A statistically significant decrease was observed in the mean litter size of infected mothers. Furthermore, the offspring showed low viability at birth and, still more, at 10 days after birth. Our data are compatible with the hypothesis that genital mycoplasma infection plays a role in reproductive failure.
Three different species of mycoplasmas--M. hominis, M. fermentans, and Ureaplasma urealyticum--have been found to infect human genitalia. In the man, mycoplasmas appear to play a role in the etiology of nonspecific urethritis and prostatis. Mycoplasmas repeatedly have been cultured from the tubes of patients with acute salpingitis and a significant antibody response to the organisms during recovery has been reported. Obstetric infections and puerperal sepsis occasionally seem to be caused by mycoplasmas. These organisms also appear to induce spontaneous abortion as well as cause infertility in a small proportion of couples.
The effect on skeletal muscle of acute viral and mycoplasma infections in thirteen men of ages ranging between 20-42 years has been studied. Comparisons are made with eight healthy men in the age group 22-29 years who were confined to bed for periods of time of lengths similar to the confinement to bed of the patients. Muscle samples were taken from the thigh. Glyceraldehyde-3-phosphate (triosephosphate) dehydrogenase (TPD), lactate dehydrogenase (LDH), citrate synthetase (CS) and cytochrome oxidase (cytox) activities were measured and the ultrastructure of the muscle specimens was studied by electron microscopy. Immobilization of the healthy persons induced decreased activities of CS, but those of TPD, LDH and cytox remained unaffected. Return to normal life restored the CS activity. The activities of the four enzymes were lower in the patients than in the healthy subjects after immobilization. During normal life, the activities slowly rose to levels as those seen in the healthy subjects. In connection with the acute disease, focal ultrastructural changes within the muscle were found. The changes were similar to those reported to occur in other, more specific muscle diseases.
Mycoplasma meleagridis infection in turkey hatching eggs was eliminated by injecting eggs with a combination of tylosin and gentamicin. Hatched F1 and F2 progeny remained free of egg-transmitted infection. Contact exposure was experienced in one negative flock. Of the preincubation injection procedures studied, a drilled hole on the small end of the egg was the inoculation site easiest to administer and best tolerated by the embryo. The embryo can tolerate a dose of gentamicin sulfate injected at 10 days of incubation that would be toxic if administered before incubation. Requirements for maintaining progeny free of infection are discussed.
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