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Biomedical subjects

S Linn

Publications and source records attributed to S Linn.

At least 145 records · Page 8Linked to original sources

Epidemiology of neonatal hyperbilirubinemia.

Interview and record review data from 12,023 singleton deliveries were analyzed to determine the relationships between neonatal hyperbilirubinemia (10 mg/dL or greater) and maternal characteristics. Confounding variables were controlled by multiple logistic regression analysis. There was a statistically significant positive relationship between hyperbilirubinemia and low birth weight, Oriental race, premature rupture of membranes, breast-feeding, neonatal infection, use of the "pill" at time of conception, instrumental delivery, and history of first trimester bleeding. Maternal smoking and black race were negatively related to hyperbilirubinemia and statistically significant. In this study, other previously suspected etiologic factors such as epidural anesthesia, parity, use of oxytocin in labor, and white race were not associated with hyperbilirubinemia.

Adult↗

Excision repair of pyrimidine dimers from simian virus 40 minichromosomes in vitro.

The ability of DNA repair enzymes to carry out excision repair of pyrimidine dimers in SV40 minichromosomes irradiated with 16 to 64 J/m2 of UV light was examined. Half of the dimers were substrate for the DNA glycosylase activity of phage T4 UV endonuclease immediately after irradiation, but this limit decreased to 27% after 2 h at 0 degrees C. Moreover, the apyrimidinic (AP) endonuclease activity of the enzyme did not incise all of the AP sites created by glycosylase activity, although all AP sites were substrate for HeLa AP endonuclease II. The initial rate of the glycosylase was 40% that upon DNA. After incision by the T4 enzyme, excision was mediated by HeLa DNase V (acting with an exonuclease present in the chromatin preparation). Under physiological salt conditions, excision did not proceed appreciably beyond the damaged nucleotides in DNA or chromatin. With chromatin, about 70% of the accessible dimers were removed, but at a rate slower than for DNA. Finally, HeLa DNA polymerase beta was able to fill the short gaps created after dimer excision, and these patches were sealed by T4 DNA ligase. Overall, roughly 30% of the sites incised by the endonuclease were ultimately sealed by the ligase. The resistance of some sites was due to interference with the ligase by the chromatin structure, as only 30-40% of the nicks created in chromatin by pancreatic DNase could be sealed by T4 or HeLa DNA ligases. The overall excision repair process did not detectably disrupt the chromatin structure, since the repair label was recovered in Form I DNA present in 75 S condensed minichromosomes. Although other factors might stimulate the rate of this repair process, it appears that the enzymes utilized could carry out excision repair of chromatin to a limit near that observed at the initial rate in mammalian cells in vivo.

Chromosomes↗

Gap-filling DNA synthesis by HeLa DNA polymerase alpha in an in vitro base excision DNA repair scheme.

The ability of HeLa DNA polymerase alpha to utilize gapped PM2 DNAs for synthesis in a model base excision DNA repair scheme was examined. Partially depurinated PM2 DNA was incised on the 5' side of apurinic sites with HeLa apurinic/apyrimidinic endonuclease II, then the baseless sugar was removed and gaps of defined mean lengths were introduced at these sites by exonucleolytic digestion with HeLa DNase V. Gaps smaller than approximately 15 nucleotides did not serve as efficient primer-templates for DNA polymerase alpha. Gaps with mean lengths of 20-63 nucleotides did support limited DNA synthesis, but such synthesis terminated after the gap was reduced to roughly 15 nucleotides. These products were not substrates for Escherichia coli DNA ligase. In contrast, HeLa DNA polymerase beta utilize as primer-templates all of the gapped DNA substrates tested though it acted more efficiently with the smaller gaps. Moreover, the beta-polymerase was capable of filling these gaps to completion. In the case of the gaps that remained after partial closure by DNA polymerase alpha, DNA polymerase beta incorporated roughly 15 nucleotides and formed a product which was a substrate for DNA ligase. These results suggest that in vivo DNA repair pathways that involve a gap-filling DNA synthesis reaction might utilize DNA polymerase alpha only for larger gaps.

DNA Polymerase II↗

The relationship between prenatal exposure to lead and congenital anomalies.

We obtained umbilical cord blood from 5,183 consecutive deliveries of at least 20 weeks' gestation and analyzed them for lead concentration. Those demographic and socioeconomic variables, including lead, which were shown on univariate analysis to be associated with increased risk for congenital anomalies were evaluated and controlled by entering them into a stepwise logistic-regression model with malformation as the outcome. Coffee, alcohol, tobacco, and marijuana use, which were associated with lead level, but not risk of malformation, were also controlled. The model was reduced in steps by eliminating the variables with the highest P value, until the most parsimonious model was created. The relative risk for anomalies associated with lead was then calculated while holding other covariates constant. Lead was found to be associated, in a dose-related fashion, with an increased risk for minor anomalies.

Abnormalities, Drug-Induced↗

Apurinic/apyrimidinic endonuclease activities appear normal in the CHO-cell ethyl methanesulfonate-sensitive mutant, EM9.

A study of the apurinic/apyrimidinic (AP) endonuclease activities of a mutant line of CHO cells, EM9, and its parental cell line, AA8, was undertaken to determine if the defective DNA repair exhibited by the mutant cell line after exposure to ethyl methanesulfonate was due to a defective AP endonuclease activity. Phosphocellulose chromatography of cell extracts resolved the AP endonuclease activities of both cell lines into two peaks as seen previously in mouse and human cells. No difference was found between the mutant and parental cell lines in the relative amount of AP endonuclease activity present in the two peaks.

Animals↗

Hydroxymethyluracil DNA glycosylase in mammalian cells.

An activity has been purified 350-fold from extracts of mouse plasmacytoma cells that forms 5-hydroxymethyluracil (alpha-hydroxythymine) and apyrimidinic sites with phage SPO1 DNA, which contains this base in place of thymine. This DNA glycosylase presumably functions to eliminate hydroxymethyluracil, a major thymine-derived DNA lesion produced by ionizing radiation and oxidative damage. The enzyme has no cofactor requirement and is active in EDTA. Neither intermediate formation nor hydrolysis of hydroxymethyl-deoxyuridine or hydroxymethyldeoxyuridine monophosphate was detected. The enzyme does not cleave apyrimidinic sites in DNA. It does release uracil from the uracil-containing DNA of phage PBS2, but this activity is less than 2% of the predominant uracil DNA glycosylase activity of the cell, which is separated by phosphocellulose chromatography. The major uracil DNA glycosylase does not release hydroxymethyluracil from SPO1 DNA. The hydroxymethyluracil glycosylase is also separated upon phosphocelluose chromatography from a thymine glycol DNA glycosylase activity that is accompanied by an apyrimidinic endonuclease activity.

Animals↗

Work and pregnancy.

Pregnancy outcomes of 7,155 women who worked between one and nine months of pregnancy were compared with outcomes of 4,018 women who were not employed. There were no differences in rates of prematurity, Apgar score, birthweight, perinatal death rate, or malformation prevalence. Working women were divided into those who left employment during the first eight months and those who worked all nine months. The latter had a lower rate of adverse outcome than the other working group and the nonworking group. This indicates that working to term in the absence of contraindications does not impose an added risk on mother or infant. After control of confounding by parity and other relevant factors, an increased risk of prolonged gestational age was seen among primiparous working women. There was an increased risk of fetal distress among those women leaving work prior to nine months who were having their third or subsequent child. A small decrease in birth weight was seen among women who left work prior to term but not among those who worked all nine months. Overall the results are reassuring that working during pregnancy is not in itself a risk factor for adverse outcome.

Adolescent↗

Causes of diarrheal disease in soldiers stationed in Lebanon and in northern Israel.

A study of acute gastroenteritis in soldiers was carried out during a 1-year period. Causes of diarrhea were compared between 33 soldiers stationed in southern Lebanon and 174 soldiers stationed in northern Israel. Shigella sp. caused 42.4% of diarrheal disease in Lebanon, compared with only 19.0% of cases in Israel. Sh. flexneri was a more common cause of bacillary dysentery in Lebanon than in Israel (71.4 vs. 18.2%, respectively), and caused a more severe illness.

Diarrhea↗

Lack of association between contraceptive usage and congenital malformations in offspring.

Previous reports have linked the use of oral contraceptives and spermicides to the occurrence of malformations in offspring. With information from 12,440 women interviewed during the delivery hospitalization, we found no relationship between contraceptive method and the occurrence of malformations. Whereas any unnecessary drug should be avoided during pregnancy, prior contraceptive method seems to be unrelated to the risk of congenital malformations.

Abortion, Induced↗

The relationship between induced abortion and outcome of subsequent pregnancies.

We analyzed interview and record review data from 9,823 deliveries to evaluate the relationship between prior history of induced abortion and subsequent late pregnancy outcomes. Complications such as bleeding in the first and third trimesters, abnormal presentations and premature rupture of the membranes, abruptio placentae, fetal distress, low birth weight, short gestation, and major malformations occurred more often among women with a history of two or more induced abortions. A logistic regression analysis to control for multiple confounding factors showed that a history of one induced abortion was statistically significantly associated with first-trimester bleeding but with no other untoward pregnancy events, and a history of two or more induced abortions was statistically associated with first-trimester bleeding, abnormal presentations, and premature rupture of the membranes. While these relationships merit further research, the results of this study are largely reassuring. A history of one or more prior induced abortions does not appear to increase substantially the risk of adverse late outcomes of subsequent pregnancies.

Abortion, Induced↗

Excision repair and DNA synthesis with a combination of HeLa DNA polymerase beta and DNase V.

The ability of HeLa DNA polymerases to carry out DNA synthesis from incisions made by various endodeoxyribonucleases which recognize or form baseless sites in DNA was examined. DNA polymerase beta carried out limited strand displacement synthesis from 3'-hydroxyl nucleotide termini made by HeLa apurinic/apyrimidinic (AP) endonuclease II at the 5'-side of apurinic sites. Escherichia coli endonuclease III incises at the 3'-side of apurinic sites to produce nicks with 3'-deoxyribose termini which did not efficiently support DNA synthesis with beta-polymerase. However, these nicks could be activated to support limited DNA synthesis by HeLa AP endonuclease II, an enzyme which removes the baseless sugar phosphate from the 3'-termini, thus creating a one-nucleotide gap. With dGTP as the only nucleoside triphosphate present, the beta-polymerase catalyzed one-nucleotide DNA repair synthesis from those gaps which lacked dGMP. In contrast, HeLa DNA polymerase alpha was unreactive with all of the above incised DNA substrates. Larger patches of DNA synthesis were produced by nick translation from one-nucleotide gaps with HeLa DNA polymerase beta and HeLa DNase V. Moreover, incisions made by E. coli endonuclease III were activated to support DNA synthesis by the DNase V which removed the 3'-deoxyribose termini. HeLa DNase V also stimulated both the rate and extent of DNA synthesis by DNA polymerase beta from AP endonuclease II incisions. In this case the baseless sugar phosphate was removed from the 5'-termini, and nick translational synthesis occurred. Complete DNA excision repair of pyrimidine dimers was achieved with the beta-polymerase, DNase V, and DNA ligase from incisions made in UV-irradiated DNA by T4 UV endonuclease and HeLa AP endonuclease II. Such incisions produce a one-nucleotide gap containing 3'-hydroxyl nucleotide and 5'-thymine: thymidylate cyclobutane dimer termini. DNase V removes pyrimidine dimers primarily as a dinucleotide and then promotes nick translational DNA synthesis.

DNA Ligases↗

Escherichia coli xth mutants are hypersensitive to hydrogen peroxide.

Escherichia coli mutants lacking exonuclease III (xthA) are exceptionally sensitive to hydrogen peroxide. They are killed by H2O2 at 20 times the rate of wild-type bacteria and at 3 to 4 times the rate of recA cells. This is the first clear phenotypic sensitivity reported for xth- E. coli and should aid in clarifying peroxide-induced lethality and the in vivo role of exonuclease III.

Catalase↗

Isolation and characterization of two chondroitin lyases from Bacteroides thetaiotaomicron.

Two chondroitin lyases were isolated from the colon anaerobe Bacteroides thetaiotaomicron. Both enzymes had similar molecular weights (104,000 and 108,000) and similar isoelectric points (8.0 and 7.9, respectively). Both enzymes were active against chondroitin sulfates A, B, and C and unsulfated polysaccharides, such as chondroitin and hyaluronic acid, although one of the enzymes was twice as active against chondroitin as the other enzyme. Both had similar Km values for chondroitin sulfates A and C (40 to 70 micrograms/ml) and for chondroitin (300 to 400 micrograms/ml). Neither enzyme could degrade the highly sulfated mucopolysaccharide heparin, but heparin was a potent inhibitor of the activity of both enzymes. Although enzymes I and II were similar in many respects, a comparison of peptides resulting from partial digestion with N-chlorosuccinimide or papain demonstrated that the two proteins are not related.

Bacteroides↗

The association of marijuana use with outcome of pregnancy.

We analyzed interview and medical record data of 12,424 women to evaluate the relationship between marijuana usage and adverse outcomes of pregnancy. Low birthweight, short gestation, and major malformations occurred more often among offspring of marijuana users. When we used logistic regression to control for demographic characteristics, habits, and medical history data, these relationships were not statistically significant. The odds ratio for the occurrence of major malformations among marijuana users was 1.36, higher than odds ratios for other exogenous variables, and the 95 per cent confidence interval was 0.97-1.91. More data are needed to establish firmly or rule out an association between marijuana usage and major malformations. Until more information is available, women should be advised not to use marijuana during pregnancy.

Abnormalities, Drug-Induced↗

The association of alcohol consumption with outcome of pregnancy.

Patterns of alcohol consumption were assessed in 12,440 pregnant women interviewed at the time of delivery. Only 92 women (0.7 per cent) reported drinking 14 or more drinks per week, with most consuming fewer than 21 drinks per week. In the crude data, alcohol intake of 14 or more drinks per week was associated with a variety of adverse pregnancy outcomes, including low birthweight, gestational age under 37 weeks, stillbirth, and placenta abruptio. After use of logistic regression to control for confounding by demographic characteristics, smoking, parity and obstetric history, only the association of placenta abruptio with alcohol consumption of 14 or more drinks per week remained statistically significant. With the exception of placenta abruptio, alcohol intake of fewer than 14 drinks per week was not associated with and increased risk of any adverse outcome. No association was seen with congenital malformations at any level of alcohol intake.

Adult↗