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Biomedical subjects

J Olsen

Publications and source records attributed to J Olsen.

At least 181 records · Page 10Linked to original sources
PubMed1998

Uptake of phenylacetic acid by two strains of Penicillium chrysogenum.

Uptake of phenylacetic acid, the side-chain precursor of benzylpenicillin, was studied in Penicillium chrysogenum Wisconsin 54-1255 and in a strain yielding high levels of penicillin. In penicillin fermentations with the high-yielding strain, 100% recovery of phenylacetic acid in benzylpenicillin was found, whereas in the Wisconsin strain only 17% of the supplied phenylacetic acid was incorporated into benzylpenicillin while the rest was metabolized. Accumulation of total phenylacetic acid-derived carbon in the cells was nonsaturable in both strains at high external concentrations of phenylacetic acid (250-3500 microM), and in the high-yielding strain at low phenylacetic acid concentrations (2. 8-100 microM), indicating that phenylacetic acid enters the cells by simple diffusion, as concluded earlier for P. chrysogenum by other authors. However, at low external concentrations of phenylacetic acid saturable accumulation appeared in the Wisconsin strain. HPLC-analyses of cell extracts from the Wisconsin strain showed that phenylacetic acid was metabolized immediately after entry into the cells and different [14C]-labeled metabolites were detected in the cells. Up to approximately 50% of the accumulated phenylacetic acid was metabolized during the transport-assay period, the conversion having an impact on the uptake experiments. Nevertheless, accumulation of free unchanged phenylacetic acid in the cells showed saturation kinetics, suggesting the possible involvement of a high-affinity carrier in uptake of phenylacetic acid in P. chrysogenum Wisconsin 54-1255. At high concentrations of phenylacetic acid, contribution to uptake by this carrier is minor in comparison to simple diffusion and therefore, of no importance in the industrial production of penicillin.

Bacteriological Techniques↗
PubMed1998

Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners.

BACKGROUND: Semen analysis is part of the routine assessment of infertile couples. WHO defines a sperm concentration above 20x10(6) per mL seminal fluid as normal. We studied the association between semen quality and the probability of conception in a single menstrual cycle in Danish couples with no previous reproductive experience. METHODS: In 1992-94, we invited 52,255 trades-union members aged 20-35 years, who lived with a partner and had no children to take part in the study; 430 couples agreed. The couples discontinued use of contraception, and were followed up for six menstrual cycles or until a pregnancy was verified within this period. Each man was asked to provide a semen sample at enrolment (which was analysed without freezing). Women kept a daily record of vaginal bleeding and sexual activity. The association between semen quality and likelihood of pregnancy was assessed by logistic regression, adjusted for sexual activity and female factors associated with low fertility. RESULTS: There were 256 (59.5%) pregnancies among the 430 couples: 165 (65.0%) among those with a sperm concentration of 40x10(6)/mL or more and 84 (51.2%) among those with lower sperm concentrations. The probability of conception increased with increasing sperm concentration up to 40x10(6)/mL, but any higher sperm density was not associated with additional likelihood of pregnancy. The proportion of sperm with normal morphology was strongly related to likelihood of pregnancy independently of sperm concentration. Semen volume and motility were of limited value in pregnancy prediction. INTERPRETATION: Our study suggests that the current WHO guidelines for normal semen quality should be used with caution. Some men with sperm counts above the lower limit of the normal range defined by WHO may in fact be subfertile.

Adult↗
PubMed1998

Perinatal correlates of specific histological types of testicular cancer in patients below 35 years of age: a case-cohort study based on midwives' records in Denmark.

Our aim was to estimate the risk of specific histological types of testicular cancer associated with perinatal factors. We conducted a case-control study with 357 cases and 704 controls born between 1950 and 1968. Cases were identified through a patient registry of all patients treated in Denmark. Data on parents' age, mothers' parity, birth weight, gestational age and undescended testes were extracted from midwives' records written shortly after delivery. The risk of testicular cancer was highest for those who has the oldest mothers (30-45 years) and for those who had the lowest parity (primipara). For newborns with 2 or more signs of prematurity (born before 8 months of gestation, birth weight below 2,500 g, birth length 40-49 cm, soft nails and undescended testis) the OR was 1.62. The association between undescended testis at birth and testicular cancer was not present for boys born after 1955. The high risk of testicular cancer among primipara was mainly seen for seminomas. All cancer types were associated with mother's age, but only the OR for teratomas was statistically significant.

Adolescent↗
PubMed1998

Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy.

OBJECTIVE: To examine the effect of alcohol consumption on the probability of conception. DESIGN: A follow up study over six menstrual cycles or until a clinically recognised pregnancy occurred after discontinuation of contraception. SUBJECTS: 430 Danish couples aged 20-35 years trying to conceive for the first time. MAIN OUTCOME MEASURES: Clinically recognised pregnancy. Fecundability odds ratio: odds of conception among exposed couples divided by odds among those not exposed. RESULTS: In the six cycles of follow up 64% (179) of women with a weekly alcohol intake of less than five drinks and 55% (75) of women with a higher intake conceived. After adjustment for cycle number, smoking in either partner or smoking exposure in utero, centre of enrolment, diseases in female reproductive organs, woman's body mass index, sperm concentration, and duration of menstrual cycle, the odds ratio decreased with increasing alcohol intake from 0.61 (95% confidence interval 0.40 to 0.93) among women consuming 1-5 drinks a week to 0.34 (0.22 to 0.52) among women consuming more than 10 drinks a week (P=0.03 for trend) compared with women with no alcohol intake. Among men no dose-response association was found after control for confounders including women's alcohol intake. CONCLUSION: A woman's alcohol intake is associated with decreased fecundability even among women with a weekly alcohol intake corresponding to five or fewer drinks. This finding needs further corroboration, but it seems reasonable to encourage women to avoid intake of alcohol when they are trying to become pregnant.

Adult↗
PubMed1998

Gene therapy strategies for treating Epstein-Barr virus-associated lymphomas: comparison of two different Epstein-Barr virus-based vectors.

B cell lymphomas in immunocompromised patients frequently contain the Epstein-Barr virus (EBV) genome (MacMahon et al, 1991), suggesting that gene therapy strategies that target EBV-positive cells for destruction might be useful for the therapy of such tumors. We have previously shown that stable expression of the cytosine deaminase (CD) gene in EBV-positive lymphoblastoid cell lines induces cell killing in the presence of the prodrug 5-fluorocytosine, with a substantial bystander killing effect (Rogers et al., 1996). To promote specific killing of EBV-positive tumor cells, we have constructed two different EBV-based vectors containing the cytosine deaminase gene. The first vector (OriP-CD), which contains the intact EBV oriP enhancer/replication element, replicates as an episome specifically in EBV-positive cells and likewise enhances transcription in an EBV-specific manner. The OriP-CD vector cannot be packaged or spread from cell to cell. The second vector (OriLyt-CD) contains the EBV lytic origin of replication (oriLyt), the EBV packaging sequences (located in the viral termini), the oriP enhancer element (but not the complete replication origin), and the EBV BZLF1 gene (which induces expression of the EBV proteins required for replication of oriLyt). The OriLyt-CD vector is replicated through the oriLyt origin specifically in EBV-positive cells and packaged as an EBV pseudovirion. The packaged oriLyt-CD virion can subsequently infect cells containing the EBV receptor, CD21, and initiate another round of replication in EBV-positive cells. Here we demonstrate that each of these two different EBV-based gene therapy strategies induces specific killing of EBV-positive B cells in vitro (in the presence of 5-FC). The advantages and disadvantages of each strategy are discussed.

Animals↗
PubMed1998

Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark.

Cancer risk in patients with cirrhosis could be modified by factors such as changes in hormonal levels, impaired metabolism of carcinogens, or alteration of immunological status. We investigated the risk of liver and various forms of cancer in patients with cirrhosis in a follow-up study. We identified 11,605 1-year survivors of cirrhosis from the files of the Danish National Registry of Patients (NRP) from 1977 to 1989. Occurrence of cancer through 1993 was determined by linkage to the Danish Cancer Registry. For comparison, the expected number of cancer cases was estimated from national age-, sex-, and site-specific incidence rates. Overall, 1,447 cancers were diagnosed among the study subjects, as compared with 708.1 expected, to yield a standardized incidence ratio (SIR) of 2.0 (95% CI: 1.9 to 2.2). In all diagnostic subgroups of cirrhosis, the risk of primary liver cancer, mainly hepatocellular carcinoma, was markedly elevated, with 245 observed cases and an overall 36-fold elevated risk (59.9-fold elevated for hepatocellular carcinoma and 10-fold for cholangiocarcinoma). Substantial and persistent excesses during follow-up were seen for all types of cancer associated with tobacco and alcohol habits (cancer of the lung, larynx, buccal cavity, pharynx, pancreas, urinary bladder, and kidney), while moderate excesses were seen for cancers of the colon and breast. The latter, however, were not complemented by any decrease in the risk of prostate cancer (SIR: 1.0; 95% CI: 0.7 to 1. 3). A slightly increased risk was seen for testis cancer, but disappeared after 10 years. We found evidence of an increased risk for liver and several extrahepatic cancers in patients with cirrhosis. Although part of this increase is likely attributable to alcohol and tobacco consumption, our study opens up the possibility that cirrhosis plays a role in the carcinogenesis of types of cancer other than liver cancer.

Adult↗
PubMed1998

Effect of N-linked glycosylation on secretion, activity, and stability of alpha-amylase from Aspergillus oryzae.

The effect of N-linked glycosylation on secretion, activity, and stability of alpha-amylase from Aspergillus oryzae grown as dispersed filaments was studied. In the presence of tunicamycin the fungus grew either as dispersed filaments or as one large pellet, whereas growth was as dispersed filaments in all control cultures. The presence of tunicamycin affected neither biomass, level of secreted alpha-amylase, nor total amount of secreted protein in cultures growing as dispersed filaments. In these cultures both glycosylated and nonglycosylated alpha-amylase appeared in the culture medium as well as in the cells, whereas in control cultures only the glycosylated form of alpha-amylase was found in the medium and in the cells. The presence of nonglycosylated alpha-amylase in the medium seemed to result from active secretion rather than from autolysis of the mycelium or extracellular deglycosylation. Deglycosylation with Endo H of crude alpha-amylase in culture filtrate did not affect its stability towards heat, acid pH, or proteolytic degradation.

Aspergillus oryzae↗
PubMed1998

Low birth weight and preterm birth after short interpregnancy intervals.

OBJECTIVE: Our purpose was to study low birth weight and preterm birth after short interpregnancy intervals. STUDY DESIGN: Follow-up of a cohort of a register-based random sample of women who had at least two live births in Denmark between 1980 and 1992. Frequency of preterm birth (gestational age <37 weeks) and low birth weight (<2500 gm) were studied as a function of the interpregnancy interval in 10,187 women. RESULTS: Short interpregnancy intervals (< or =8 months) were associated with preterm birth but not with low birth weight. The adjusted odds ratios for preterm birth were 3.60 (95% confidence interval 2.04 to 6.35) for intervals up to 4.00 months and 2.28 (1.49 to 3.48) for intervals between 4.01 and 8.00 months compared with deliveries after 24 to 36 months, in which the risk of preterm birth was 3.5%. Risks were higher in women with a previous pregnancy at term. Social status, age, and parity were adjusted for. CONCLUSIONS: Short interpregnancy intervals were associated with an increased risk of premature delivery. This risk should be taken into account when planning a new pregnancy.

Cohort Studies↗
PubMed1998

Use of antibiotics during pregnancy.

OBJECTIVE: To describe the occurrence and distribution of antibiotic treatments, in addition their indications in control pregnant women in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. RESULTS: Of 38 151 control pregnant women who delivered later newborn infants without congenital abnormality, 6554 (17.2%) were treated by antibiotics. Most women (14.5%) had penicillin, while 1.2% and 0.7% of pregnant women were treated by cephalosporins and tetracyclines, respectively. More than 100 pregnant women used the following antibiotics: ampicillin (6.9%), penamecillin (5.9%), cefalexin (1.0%), phenoxymethylpenicillin (0.6%), oxytetracycline (0.5%), erythromycin (0.45%), benzylpenicillin-procain (0.4%) and benzylpenicillin+benzylpenicillin-procain (0.3%). Different antibiotics had different indications for treatment. The mean birth weight was significantly lower in the treated group compared to the untreated group. PRACTICAL IMPLICATIONS: Different antibiotics have different chemical structures and indications for treatment. Therefore it is not appropriate to evaluate their teratogenic potential of combined antibiotic groups. There may be many interactions between underlying maternal diseases, other drug uses, further confounding factors and antibiotics studied, thus adequate controls are needed to estimate the adjusted teratogenic odds-risk ratios. European countries have different spectrum of antibiotic use. It would be necessary to know these baseline data of different populations. The anxiety and fear created by the notion that nearly all drugs cause congenital abnormalities may be more harmful than some proven human teratogenic drugs themselves. Thus a better risk-benefit estimation for antibiotic uses during pregnancy is an urgent and important task.

Abnormalities, Drug-Induced↗