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A facile synthesis of adenosine 3', 5'-cyclic methylphosphonate (1) and 3', 5'-cyclic methylphosphonothioate (2) was accomplished by treatment of 2'-protected adenosine with O,O-bis (1-benzotriazolyl) methylphosphonate or O,O-bis (1-benzotriazolyl) methylphosphonothioate under mild conditions, respectively. The ability of the compounds to inhibit DNA synthesis in mice hepatoma was tested. A pair of diasteromers of 2'-protected (1) was separated and the configuration at the phosphorus atom was identified.

Human bronchoalveolar cells, consisting of approximately 85% pulmonary alveolar macrophages (PAMs), and peripheral blood lymphocytes isolated from healthy volunteers were investigated for their ability to metabolize 7,8-diol of benzo[a]pyrene (B(a)P). The mutagenicity of reactive metabolites was analyzed by employing a co-cultivation system using V79 Chinese hamster cells for the detection of mutations. The metabolic activity of the human cells was compared to PAMs isolated from rabbits. The number of PAMs obtained by bronchoalveolar lavage of smokers was found to be significantly elevated compared with nonsmokers. However, the mean number of induced mutations of the 7,8-diol mediated by PAMs during co-cultivation did not differ significantly between smokers and nonsmokers. The aryl hydrocarbon hydroxylase (AHH) activity of human lymphocytes has been studied by others, but to the best of our knowledge this is the first demonstration that human blood lymphocytes could be successfully used in a co-cultivation assay for the characterization of xenobiotic metabolism in terms of mutations, as illustrated by the linear increase of induced mutations in the V79 cells. Rabbit PAMs were less efficient in mediating mutations as compared to both smokers' and nonsmokers' PAMs or lymphocytes. This can probably be explained by less efficient bioactivation of 7,8-diol in rabbit PAMs, which is supported by the fact that the rabbit PAMs metabolized B(a)P in a different way as compared to human PAMs as revealed by HPLC analysis of ethyl acetate extractable metabolites of 3H-B(a)P. No qualitative or quantitative difference in the patterns of B(a)P metabolism by PAMs isolated from smokers and nonsmokers could be established. In conclusion, human PAMs were found to be more efficient in terms of cell-mediated mutagenicity than human lymphocytes, which are more efficient than rabbit PAMs. The present results differ from previous reports concerning the xenobiotic metabolizing capacity of these cells assessed by other methods. This illustrates the usefulness of the co-cultivation assay, because it measures not only the bioactivating capacity of isolated mammalian cells, but also their detoxifying capacity, the transfer of mutagens to other cells and the ability of their metabolites to cause mutations.

Electron microscopy of purified Chlamydia trachomatis treated by various physical and chemical means shows that the envelope of the elementary bodies (EB) consists of the outer cell wall layer, the inner cell wall layer, and the inner membrane. The outer cell wall layer is mainly made up of granular subunits arranged in a hexagonal pattern and may be called the "mural structural protein layer". It forms together with the inner cell wall layer the rigid cell wall. The inner or protoplasmic membrane is not easily shown in the young EB. In the negatively stained specimen, a frail and easily removable superficial layer is seen adhering to the "mural structural protein layer". But in ultra-thin sections this superficial layer is not shown separately. There are fold-like grooves which are special structures probably related to reproduction. There are seen some EB's in binary fission, and a number of bodies very big in size yet having morphological characteristics of the EB's, which are in various processes of multiplication, such as binary fission, budding, and "multicentered germination". These observations give a challenge to the current opinion that only the initial bodies have the power of reproduction.

An epidemiologic survey on Campylobacter jejuni infection in a nursery was made in April 1987. It was found that there was a spread of C. jejuni high infection. Two cooks affected by enteritis of C. jejuni were considered to be a reservoir of the infection. Stool cultures were positive for C. jejuni in 43 out of 187 children, with a positive rate of 23%. Eight of the 43 had diarrhea and the others were asymptomatic carriers (24.3%). Controls were set up in another nursery with 238 healthy children and 201 non-diarrheal outpatients; C. jejuni was positive for 11.4% and 7.5%, respectively. The difference was quite significant (P less than 0.005). Results of biotyping on the strains isolated from the two cooks and the children in the nursery showed that all were of C. jejuni biotype 1, except two (4.7%) of the strains from the children, which were E. coli. The authors have suggested that transmission of C. jejuni in the nursery may be caused by contaminated food or person-to-person contact.

The aim of the present investigation was to screen for rare types of spontaneously occurring mutational events in order to provide information on the organization of the mammalian genome. For this purpose a hierarchical sequence of analyses is used with a first step utilizing a forward reverse mutation approach. The present paper deals with the characterization of 22 isolated mutants from 2 groups, 11 spontaneously appearing mutants and, in comparison, 11 ethyl methanesulfonate-induced mutants at the HPRT locus in V79 Chinese hamster cells, by means of reverse mutation analyses using selection with medium containing L-azaserine. Nine out of the 11 mutant clones of each group could be reverted either spontaneously or induced by treatments with ethyl nitrosourea (ENU), ICR191 or 5-azacytidine (5AC), which indicates that they were caused by point mutations. Two of the revertible mutant clones of spontaneous origin were found to be resistant to HAT but not HAsT medium. These 2 6TGrHATr mutants were the only mutants isolated which could be affected by 5AC with a significant increase in reversion frequency. Chromosome aberration analysis did not indicate any enhancement in aberration frequency in the X-chromosome by 5AC treatment. Studies on the mutagenicity at the OUA locus indicated that the 5AC- and ENU-induced mutation frequencies in these 2 mutants were comparable to the effects in the parent wild-type cell line. Their cellular incorporation of 3H-hypoxanthine was enhanced in the presence of aminopterin, but decreased with L-azaserine indicating that they were phosphoribosyl pyrophosphate (PRPP) mutants. On the basis of these results, it is hypothesized that reversion of these 2 6TGrHATr mutants may occur by a gene amplification mechanism and that this process may be facilitated by 5AC treatment.

From March to May 1987, 798 children under 7 years of the outpatients in Chengdu district were examined and their stool samples cultured for Campylobacter jejuni/coli. C. jejuni/coli was isolated from 31 (9.51%) of 326 children with diarrhea and 22 (4.66%) of 472 children with non-diarrhea. The difference was significant (P less than 0.05). This result indicated that C. jejuni/coli is an important pathogen of children diarrhea in Chengdu district. Meanwhile, by inquiry we investigated risk factors related with C. jejuni/coli infections. Case group was consisted of 53 children with C. jejuni/coli positive. For each case, 3 controls were chosen from 745 children with C. jejuni/coli negative and matched according to age (less than 6 month), sex, living place (city or countryside), way of feeding, and whether to have diarrhea or not. The results has shown that contact with animals a week before being ill and habit of intake of food with hands are risk factors of C. jejuni/coli infection of childhood in Chengdu, with an odd ratio of 2.97 and 2.71 respectively. This provides valuable information about the prevention of C. jejuni/coli infection.

A case-control study of hypertension of 140 pairs indicated that inherited susceptibility and harmful life style were quite important risk factors in increasing the development of hypertension. The effects could be taken place by their interaction. Changing life style could be taken as one of the significant measures for preventing hypertension among population with inherited susceptibility.

Methyl, n-butyl 2'-TBDMS-N2-DMF-guanosine 3',5'-cyclic phosphate and 2'-TBDMS-N2-DMF-guanosine 3',5'-cyclic diethyl-phosphoramidate were synthesized by reaction of protected guanosine with trivalent phosphorus reagents in the presence of tetrazole followed by oxidation. The reaction occurred stereospecifically. Protected guanosine 3',5'-cyclic phosphotriesters and N, N'-diethyl-phosphoramidate were shown to have inhibitory activity on the synthesis of DNA and RNA in mouse liver tumor cell. Diastereoisomers of n-butyl N2-substituted guanosine 3',5'-cyclic phosphate have been shown to activate adenylate cyclase in vitro.

Bay o 2752 [N,N'-(1, 11-undecandiyl)bis(2,3-dihydro-2-methyl-1H-indole-1-carboxamide)] has been demonstrated in rats to inhibit intestinal cholesterol absorption. Studies were carried out in male Wistar rats to determine if the mechanism is inhibition of intestinal bile acid absorption or cholesterol esterification. Bay o 2752 did not alter intestinal bile acid absorption as measured by in vitro uptake of [14C]taurocholic acid into ileal everted sacs (0.01 and 1.0 mg/ml of Bay o 2752) or the biliary excretion of radioactivity after in vivo ileal perfusion of the bile acid and drug (1.0 mg/ml at 1.0 ml/min for 1 hr). Cholesterol esterification was determined by measurement of in vitro activity of acyl coenzyme A:cholesterol acyltransferase from hepatic microsomes and cholesterol ester hydrolase from pancreatic supernatant, and the in vivo lymphatic output of cholesteryl ester after intraduodenal cholesteryl infusion. Addition of Bay o 2752 (0.01-10 micrograms/ml) to hepatic microsomes produced a concentration-dependent decrease in acyl coenzyme A:cholesterol acyltransferase activity with an IC50 of 0.95 micrograms/ml. Cholesterol ester hydrolase activity was unaffected by the drug (1.0-100 micrograms/ml). Intraduodenal infusion of Bay o 2752 (10 mg/ml at 0.9 ml/hr for 8 hr) reduced markedly the flux of cholesterol from the intestinal lumen into the mesenteric lymph, especially the lymphatic output of the esterified form of both radioisotopically labeled and total cholesterol. These data suggest that Bay o 2752-induced reduction in intestinal cholesterol absorption results from its potent inhibitory effect on acyl coenzyme A:cholesterol acyltransferase activity.