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Biomedical subjects

H Peterson

Publications and source records attributed to H Peterson.

At least 55 records · Page 3Linked to original sources

Differences in temporal aspects of mutagenesis and cytotoxicity in Chinese hamster cells treated with methylating agents and thymidine.

Equitoxic concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and methyl methanesulfonate (MeMes) produced different frequencies of 8-azaguanine-resistant mutants and different amounts of N7-methylguanine, O6-methylguanine (m6G), and N3-methyladenine in the DNA of V79 Chinese hamster cells. Thus, neither the cytotoxicities nor the mutagenicities of these methylating agents could be attributed solely to nitrogen or to oxygen methylations in the DNA. However, MNNG produced 12-fold more m6G and 5-fold more mutants than did MeMes, indicating that a substantial part of the MNNG-induced mutations resulted from m6G--thymine mispairing during DNA replication. The expression as mutants of mutagenic oxygen methylations in the DNA of cells treated with MNNG was enhanced by thymidine (dThd) and deoxycytidine (dCyd), but these nucleosides did not significantly enhance MeMes-induced mutagenesis. The cytotoxicities of MNNG and MeMes were also increased by 10 microM dThd in proportion to the amount of m6G in the DNA. These increases in cytotoxicity were abolished by dCyd, which did not greatly reduce the dThd-induced enhancements of mutagenesis. Moreover, when dThd was present only during the 2-hr treatment with MNNG, maximal cytotoxicity occurred, but MNNG-induced mutagenesis was not increased. Maximal mutagenesis occurred when the dThd was present throughout the first doubling time of the MNNG-treated cells. Thus, the expression of the cytotoxicity and the mutagenicity associated with m6G in the DNA of V79 cells occurred by quite different mechanisms.

Alkylating Agents↗

Antibodies to lipid A during urinary tract infection.

Serum levels of antibodies to lipid A were determined with an enzyme-linked immunosorbent assay in 26 girls with their first known symptomatic urinary tract infection (UTI) and in 15 girls with asymptomatic bacteriuria (ABU). Also included were six female patients with recurrence of acute upper UTI, five of whom had renal changes after the infections; 28 female patients with renal scarring but not symptomatic UTI at the time of investigation; and uninfected individuals. IgG and IgM antibodies to lipid A were found in approximately 50% of the uninfected children older than two years of age. Girls with acute cystitis, acute pyelonephritis, or ABU showed significantly elevated levels of IgG antibodies to lipid A as compared with children with no history of UTI. High levels of IgG antibodies to lipid A may be indicative of severe renal infection and development or progression of renal parenchymal reduction. The diagnostic value of determining levels of antibodies to lipid A is discussed.

Adolescent↗

Adhesion of Streptococcus pneumoniae to human pharyngeal epithelial cells in vitro: differences in adhesive capacity among strains isolated from subjects with otitis media, septicemia, or meningitis or from healthy carriers.

A method was developed to study the adhesion of Streptococcus pneumoniae to human pharyngeal epithelial cells. Epithelial cells from healthy persons, pneumococcal strains from patients with otitis media, meningitis, or septicemia, and pneumococcal cells from the nasopharynx of healthy carriers were used. Adhesion was found to be influenced by changes in the bacterial incubation medium and growth phase, the concentration of bacteria and epithelial cells, the epithelial cell donor, the incubation time and temperature, and the pH and osmolarity of the incubation medium. Pretreatment of bacteria with heat, Formalin, or trypsin decreased adhesion. The highest adhesion was obtained when 10(9) bacteria cultivated for 18 h in streptococcus cultivation broth were added to 10(4) pharyngeal cells and incubated at 37 degrees C for 30 min. S. pneumoniae strains from patients with frequent episodes of otitis media and strains from healthy carriers had the highest adhesion values; septicemia and meningitis strains had the lowest. The capsular polysaccharide type did not determine the adhesive capacity of the strains, but otitis strains belonging to the capsular types often associated with otitis media adhered in high numbers. Adhesion may be important for pneumococci colonizing the nasopharynx or inducing otitis media.

Carrier State↗

Oncogenic transformation and mutation of C3H/10T 1/2 clone 8 mouse embryo fibroblasts by alkylating agents.

Two-hr treatments with N-methyl- and N-ethyl-N'-nitro-N-nitrosoguanidines and ethyl methanesulfonate induced ouabain-resistant mutants in C3H/10T 1/2 cells. The alkylnitronitroso-guanidines gave linear dose-response curves and were more potent mutagens than were ethyl methanesulfonate and methyl methanesulfonate. These differences in potency were largely due to differences in the half-lives of the alkylating agents in culture medium. Differences in mutation frequencies at equitoxic concentrations of the alkylating agents are considered to reflect differences in the chemical mechanisms of alkylation and mutagenesis by the compounds. However, the frequencies of mutations produced at equitoxic concentrations were not uniformly associated with the nucleophilic selectivities of the compounds as expressed by their published Swain-Scott substrate constants. Whether or not followed by repeated replating, the yield of oncogenically transformed foci of asynchronous cells after treatment with the alkylating agents was so low that we could not obtain dose-response curves, and the yield may not be significant. By contrast, in previous experiments with N-methyl-N'-nitro-N-nitrosoguanidines and polycyclic hydrocarbons in Syrian hamster embryo fibroblasts and with ultraviolet light and polycyclic hydrocarbons in C3H/10T 1/2 cells, transformation occurred to an equal or greater extent than mutation measured in the same cells.

Alkylating Agents↗

Facilitation by pyrimidine deoxyribonucleosides and hypoxanthine of mutagenic and cytotoxic effects of monofunctional alkylating agents in Chinese hamster cells.

Hypoxanthine (Hx), thymidine (TdR) and deoxycytidine (CdR), at concentrations of 10(-5) M increased the yield of 8-azaguanine-resistant (AzGr) mutants induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in cultured Chinese hamster V79 cells. The cytotoxicity of MNNG was increased 2-fold in the presence of Hx, and more than 10-fold in the presence of TdR. This cytotoxic effect of TdR was abolished by equal concentrations of CdR, which by itself did not increase the cytotoxicity of MNNG. However, the yield of MNNG-induced AzGr colonies was increased 2--10-fold in the presence of both CdR and TdR. The AzGr colonies displayed phenotypes characteristic of hypoxanthine: guaninephosphoribosyltransferase-deficient (HGPRT-) mutants, or indicative of mutant HGPRT with altered substrate affinities. The nucleosides did not affect the growth or expression time of the HGPRT- mutants; the same extent of alkali-labile DNA damage occurred in cells treated with alkylating agents in the presence and absence of TdR and CdR; and the increase in mutation frequency in the presence of these nucleosides occurred not only with MNNG, but also with ethylating agents. Nucleosides treated with MNNG were not mutagenic, and treatment of the cells with TdR and CdR only prior to treatment with MNNG or only during selection with AzG did not increase the induced mutation frequency. Therefore, the interpretation is proposed that CdR, TdR and Hx produce nucleotide-pool imbalances that increase lethal and mutagenic errors of replication of alkylated DNA.

Animals↗

Autoantibodies to Tamm-Horsfall protein associated with urinary tract infections in girls.

Girls with various forms of urinary tract infections and a reference material were analyzed for autoantibodies in serum to the Tamm-Horsfall glycoprotein. Such antibodies could be detected in all sera analyzed. In the control subjects cord blood contained very low IgA and IgM anti-TH, which increased significantly up to the age of 8 months. The IgG anti-TH levels in cord blood correlated with maternal levels. After the age of 2 months the IgG anti-TH followed the anti-TH levels of the other immunoglobulin classes. Among the infants aged 2 to 7 months with acute UTI, no anti-TH increases were found. In girls more than one year of age with acute nonobstructive UTI, IgG and IgA anti-TH levels were significantly higher in those with acute pyelonephritis and reflux, with or without parenchymal reduction, than in those with acute pyelonephritis and normal radiologic findings. The latter group had significantly higher levels of IgG and IgA but not IgM anti-TH than did those with acute cystitits. In contrast, girls with renal parenchymal reduction but no signs of infection at the time of testing had significantly depressed anti-TH levels compared to control values.

Adolescent↗

Chronic granulomatous disease in three siblings.

A family of 7 persons is described in which one male and two female siblings have chronic granulomatous disease (CGD). The CGD diagnosis was established by histories of recurring infections, typical histopathology, deficient nitroblue tetrazolium (NBT) reduction and deficient neutrophil killing of Staphylococcus aureus. Noteworthy infections were liver abscesses, pneumonia, pleurisy, lymphadenitis, skin pustules, urinary tract infection and dental abscesses. The affected boy was the most severely ill with liver abscesses. One sister also had liver abscesses with Staph. aureus and both were treated with cloxacillin in combination with fucidin and surgical intervention. A survey of the closest relatives with the NBT test disclosed no further cases. In this family in the heredity seems to be of the recessive type.

Adolescent↗

Fibrinolysis and antifibrinolytic drugs in the growth and spread of tumours.

In the last few years increased release of fibrinolytic enzymes from malignant cells has been observed, but the significance of this property in relation to malignant growth is still not fully understood. Antifibrinolytic drugs decrease the growth rate of some experimental tumours and might have a similar effect on human malignant tumours. Antifibrinolytic drugs might also decrease the intravascular shedding of tumour cells from primary tumours, but might on the other hand enhance the lodgement of those metastatic tumour cells already in the vascular bed of recipient organs.

Animals↗

The influence of serum components on the growth and mutation of Chinese hamster cells in medium containing 8-azaguanine.

Low concentrations (less than or equal 20 mug/ml) of 8-azaguanine are 1000 fold more toxic to V79 Chinese hamster cells in medium containing 10% dialyzed fetal calf serum than in medium containing 10% undialyzed serum. Serum enzyme activity that converts AG to nontoxic 8-azaxanthine degrades AG at the same rate, whether or not the serum is dialyzed. However, cytotoxicity results similar to those obtained with US were produced in medium containing DS and 2.5 mug of hypoxanthine (HX)/ml (DSH). Therefore, serum HX is considered to be responsible for the relatively low cytotoxicity of AG in medium containing US. Colonies that arose in medium containing AG were isolated and characterized. Those that remained resistant to AG (40 mug/ml) and sensitive to aminopterin in the presence of HX and thymidine (HAT) were considered mutants; non-mutants were sensitive to AG and resistant to HAT. Colonies isolated from medium containing DSH or US and low concentrations of AG were not mutants, but those from medium containing high concentrations (greater than or equal 30 mug/ml) of AG were mutants. Spontaneous and N-methyl-N-nitro-N-nitrosoguanidine induced mutants were detectable in medium containing DSH without replating the cells prior to adding AG (greater than or equal 30 mug/ml), but in order to detect MNNG induced mutations in medium containing DS replating was essential. In DS, the mutation frequency increased as an exponential function of the toxicity of MNNG, but remained two orders of magnitude lower than the induced mutation frequencies that occurred in DSH. HX, in DSH or US, produced profound effects, other than interference with AG toxicity, that distort the results of mutagenesis assays. To study mutation using AG resistance as the endpoint, it is essential to use dialyzed serum.

Azaguanine↗