Cytotoxic and immunoregulatory function of intestinal lymphocytes in Chlamydia trachomatis proctitis of nonhuman primates.

To study the role of natural killer cells and immunoregulatory T cells in the pathogenesis of proctitis due to Chlamydia trachomatis (L2 serovar), lymphocytes were obtained from the rectal mucosa and other sites of nonhuman primates and studied by using phenotypic and functional assays. In animals with lymphogranuloma venereum (LGV) proctitis, the percentage of lymphocytes with the natural killer cell phenotype (Leu-11+) was not significantly higher at any site in LGV infection, and natural killer cell function of lymphocytes isolated from the rectum was lower during LGV infection. This was not due to the suppressive effect of factors in serum, rectal lymphocytes, or LGV elementary bodies. In studies of regulatory T cells, the Leu-3+/Leu-2+ ratio was lower in the peripheral blood and the spleen during LGV infection, but the ratio did not decrease in lamina propria T cells. Both peripheral blood and rectal lymphocytes had higher helper T-cell function for polyclonal immunoglobulin G (IgG) synthesis in pokeweed mitogen-stimulated cultures 2 weeks following LGV infection. Increased suppressor T-cell function for pokeweed mitogen-stimulated IgG synthesis was found only in the peripheral blood of animals 2 weeks after infection, but not in isolated rectal lymphocytes. These results indicate that in LGV proctitis natural killer cells are not an important component of the inflammatory infiltrate at the site of infection, and helper T-cell function increases in peripheral blood and rectal lymphocytes.     

Molecular aspects of catechol and pyrogallol inhibition of liver microsomal lipid peroxidation stimulated by ferrous ion-ADP-complexes or by carbon tetrachloride

Summary Lipid peroxidation was induced in rat liver microsomes either by iron-ADP-complexes or by carbon tetrachloride in the presence of NADPH. Different compounds containing catechol or pyrogallol structures were examined for their activities to inhibit lipid peroxidation in both systems. In general, all compounds tested showed similar inhibitory activities on lipid peroxidation, if induced by ferrous ion-ADP-complexes or by carbon tetrachloride. This inhibition is explained by the suggestion that catechols and pyrogallos inhibit at the lipid site of the membrane, rather than at the enzymic site. Compounds not containing catechol or pyrogallol groups inhibited lipid peroxidation only weakly. O-Methylation resulted in a decrease of the inhibitory effect. Catecholor pyrogallol-derivatives which contained polar functional side chains, like carboxyl- or amino groups showed minor inhibitory effects compared to the esterified or N-alkylated compounds.Dihydroxychlorpromazine, 2-hydroxy-estradiol and 2-hydroxyethinylestradiol were the most effective inhbitors of microsomal lipid peroxidation (I₅₀-values of 1×10^–6 to 2×10^–7 M). The inhibitory activity of -tocopherol, glutathione and ascorbic acid, naturally occurring antioxidants, was about three orders of magnitude lower.Inhibition of lipid peroxidation induced by NADPH-cytochrome c reductase and iron-ADP-complexes in the presence of NADPH and liposomes was also observed with catechols.From our results we assume that the molecular structure of a catechol or pyrogallol functional group is a prequisite for an effective inhibition of lipid peroxidation by these chemicals. Furthermore, the results are discussed in relation to the requisite membrane affinity of catechols, pyrogallols and other antioxidants which might be used for inhibition studies on lipid peroxidation in vivo.     

The significance of covalent binding of catechols to proteins in vivo

When rats were dosed with 14 g/kg ³H-isoproterenol, ³H-radioactivity was measurable in the liver until 48 h. This amount was not different in livers of animals which have been pretreated with diethyl maleate.After exhaustive extraction, a significant amount of ³H-radioactivity from isoproterenol could be detected in the proteins of total liver (homogenate), of cytosol and of microsomes. In the cytosol fraction of diethyl maleate pretreated animals twice the amount of isoproterenol-radioactivity was found in the extracted proteins compared to controls. In the microsomal fraction there was no difference between diethyl maleate pretreated and control animals in the amount of radioactivity incorporated into proteins.In all fractions the radioactivity measurable in the extracted proteins declined with a half life time of about 24 h.The in vivo results on covalent binding of isoproterenol are compared to the irreversible protein binding of ethinyloestradiol in vivo. Quantitatively, these in vivo data are compared to the results on irreversible protein binding obtained during incubations of isoproterenol or ethinyloestradiol with rat liver microsomes.Presented at the Symposium Influence of Metabolic Activations and Inactivations on Toxic Effects held at the 18th Spring Meeting of the Deutsche Pharmakologische Gesellschaft, Section Toxicology, D-6500 Mainz, March 15, 1977     

Detection of Chlamydia trachomatis cervical infection: a comparison of Papanicolaou and immunofluorescent staining with cell culture

We compared tissue culture with Papanicolaou-stained cervical smears, endocervical cytologic smears stained with immunofluorescent monoclonal antibody, and a direct immunofluorescent stain of cervical specimens (MicroTrak) for detection of Chlamydia trachomatis in cervical specimens. Fifty-one (21%) of 245 women had positive cultures for C. trachomatis, 14 (27%) of whom had clinical evidence of cervicitis. With the criteria of intracytoplasmic coccoid inclusion bodies within metaplastic cells, 45 (34%) of 130 Papanicolaou smears were read as suggestive for C. trachomatis. Seventeen of the 45 positive Papanicolaou smears were positive on culture and 28 were negative (sensitivity 54%, specificity 71%). In contrast, 48 of 51 women with positive cultures and one woman with a negative culture had positive immunofluorescent-stained cytologic smears (sensitivity 94%, specificity 99%, with positive predictive value of 98%). Similarly, 47 of 51 women with positive cultures also had positive results with MicroTrak direct immunofluorescent stain, with only one positive specimen in 196 women with negative cultures (sensitivity 92%, specificity 99%, with positive predictive value of 98%). This study demonstrates that immunofluorescent staining of cervical specimens or of cytologic smears is a more sensitive and specific method than routine Papanicolaou smear for detection of chlamydia infection in a high-prevalence population.     

Changes in the classification of carcinogenic chemicals in the work area

Carcinogenic chemicals in the work area are currently classified into three categories in section III of the German List of MAK and BAT Values (list of values on maximum workplace concentrations and biological tolerance for occupational exposures). This classification is based on qualitative criteria and reflects essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. It is proposed that these categories – IIIA1, IIIA2, IIIB – be retained as Categories 1, 2, and 3, to correspond with European Union regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, these three categories are supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not contribute significantly to risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. Chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures, are classified in Category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose-response relationships and toxicokinetics, and for which risk at low doses can be assessed are classified in Category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for Category 4 (1,4-dioxane) and Category 5 (styrene) are presented.     

Die gewebsverteilung von 1,2-14c-vinylchlorid bei der ratte

Zusammenfassung Wird Vinylchlorid aus der Atmosphere eingeatmet, so stellt sich ein Gleichgewicht zwischen dem Vinylchlorid in der Luft und dem Organismus ein. In erster Linie reichert sich nicht metabolisiertes Vinylchlorid im Fettgewebe an. Für dieses Verteilungsverhalten dürfte die Lipophilie des Vinylchlorid Ausschlag gebend sein. Das Konzentrationsverhältnis von Vinylchlorid in einzelnen Organen bleibt über den gesamten untersuchten Konzentrationsbereich von 25 his 10.000 ppm Vinylchlorid in der Expositionsatmosphäre konstant. Aus dem Gleichgewicht wird Vinylchlorid dem Metabolismus zugeführt. Metabolite reichern sich, im Gegensatz zum unveränderten Vinylchlorid, vor allem in Leber und Niere an.     

Treatment of obstetric and gynecologic infections with cefamandole.

Cefamandole nafate is a derivative of 7-aminocephalosporanic acid which has been shown to have good in vitro activity against aerobes traditionally susceptible to cephalosporins as well as many anaerobes, including B. fragilis. One hundred women with obstetric or gynecologic infections completed treatment with cefamandole: 53 had post-cesarean section infections: 24, acute pelvic inflammatory disease: 16, posthysterectomy cuff cellulitis/abscess; and seven, vulvar or abdominal wound abscess. Almost 90% of these women had either polymicrobial aerobic/anaerobic bacterial infections or an anaerobic infection alone. Ninety women responded to cefamandole alone; in 10 cases chloramphenicol was added, but in addition five of these women required surgical therapy for eradication of infection. Mild to severe phlebitis at the infusion site that responded to conservative therapy was demonstrated in 14 women. Of 312 bacterial isolates from these women, 89% were sensitive to cefamandole at 32 microgram/ml, an easily achievable serum level; 93% of anaerobic streptococci, the most common isolates, were sensitive at 32 microgram/ml. Also, 90% of all Bacteroides species were susceptible at 32 microgram/ml; 82% of B. fragilis were susceptible at this concentration. These data indicate that cefamandole is safe and effective for treatment of women with polymicrobial pelvic infections but that approximately 5% of these women will require surgical exploration in addition to antimicrobial administration.     

Results of testing for intestinal parasites by state diagnostic laboratories, United States, 1987.

We analyzed results of 216,275 stool specimens examined by the state diagnostic laboratories in 1987; parasites were found in 20.1%. Percentages were highest for protozoans: Giardia lamblia (7.2%), Entamoeba coli and Endolimax nana (4.2% each), Blastocystis hominis (2.6%), Entamoeba histolytica (0.9%), and Cryptosporidium species (0.2%). Identifications of Giardia lamblia increased broadly from the 4.0% average found in 1979, with 40 states reporting increases and seven decreases. Most states that identified Giardia in more than 9% of specimens were located around the Great Lakes or in the Northwest. Seasonally, Giardia identifications increased in the summer and fall, especially in northern states. The most identified helminths were nematodes: hookworm (1.5%), Trichuris trichiura (1.2%), and Ascaris lumbricoides (0.8%). Other less commonly identified helminths included Clonorchis and Opisthorchis species (0.6%), Strongyloides stercoralis (0.4%), Hymenolepis nana (0.4%), Enterobius vermicularis (0.4%), and Taenia species (0.1%). Tape tests for Enterobius, reported for 35 states, were positive for 11.4% of 9,597 specimens. Nine states (California, Colorado, Hawaii, Idaho, New Jersey, Oregon, Rhode Island, Washington, Wisconsin) reported hookworms in more than 2% of specimens; none were states traditionally associated with indigenous transmission. Cryptosporidium diagnoses, reported by 25 of 49 states, were recorded for the first time in a national survey and showed no marked regional clustering. The Giardia data revealed changes in rates of identification and in geographic patterns compared with state laboratory data collected a decade earlier (1976-1978).     

Economical laboratory support system for influenza virus surveillance.

When increases in influenzalike illnesses were first detected during the 1984 to 1985 and 1985 to 1986 influenza seasons, throat swab specimens were mailed by physicians across the United States to one hospital laboratory, and each specimen was inoculated into a single tube of cell culture. Of 165 specimens, 52 (32%) were positive for influenza A or B virus within 3 days of receipt when tested by fluorescence microscopy, permitting positive results to be received by the physicians within 1 week on the average. Approximate direct cost was $16 per specimen.