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Biomedical subjects

L Nylund

Publications and source records attributed to L Nylund.

At least 19 recordsLinked to original sources

Genotoxic effects and chemical compositions of four creosotes.

Four creosotes used in Finland for impregnating wood were tested in the Ames Salmonella test, the SCE test and the SOS chromotest. Compounds volatile at 37 degrees C were assayed using the taped plate testing protocol. The creosotes were fractionated according to their natural boiling ranges and the fractions were tested in the Ames Salmonella assay. Chemical compositions of creosotes and fractions were determined by high resolution gas chromatography/mass spectrophotometry techniques and by reversed phase high performance liquid chromatography. Mutagenic activities were shown to reside in fractions having the highest boiling point ranges (greater than 290 degrees C). The concentrations of mutagenic polycyclic aromatic hydrocarbons in creosotes and in some of their corresponding distillation fractions, when compared with mutagenic activities, indicated synergistic or antagonistic interactions.

Animals

Mutagenicity testing of protein-containing and biological samples using the Ames/Salmonella plate incorporation test and the fluctuation test.

Mutagenicity testing of biological samples and proteins is complicated by the presence of histidine and histidine-related growth factors which may produce a false positive result in the Ames/Salmonella plate incorporation test. A bioassay method, utilizing an automated dispenser-photometer and Salmonella typhimurium strain TA1535 as the indicator bacteria, was used to estimate the presence of histidine-related growth factors in three enzyme solutions submitted for mutagenicity testing. One of the solutions was clearly positive in the Ames/Salmonella test and also contained the highest amount of L-histidine-HCl-equivalents. The two other solutions, with low or undetectable amounts of L-histidine-HCl-equivalents, gave equivocal and negative results, respectively, in the Ames/Salmonella test. Studies were also performed with strains TA98, TA100 and TA1535 to determine the amount of added L-histidine-HCl that would result in a 'positive' result in the Ames/Salmonella test. Because the minimum amount of L-histidine-HCl required to double the number of revertant colonies was 150 nmol/plate, and the maximum amount of L-histidine-HCl-equivalents supplied by the enzyme preparations was 40 nmol/plate at the highest tested dose, the mutagenicity test results of the enzyme solutions cannot be explained solely by histidine or related compounds. Smokers' and non-smokers' urines, concentrated with liquid extraction (CHCl3) and adsorbent (XAD-2 and XAD-2/Sep-Pak C18) techniques, were studied to reveal differences in efficiencies to extract histidine and histidine-related compounds in the urines. Amounts of 'histidine' in concentrates of urine were measured using the bioassay method and a chemical method employing derivatization with fluorescamine. The fluorescamine method also efficiently detected 3-methyl-L-histidine, a product of muscle metabolism excreted in urine, which was found to be unable to support auxotrophic growth in TA1535, leading to exaggerated estimations of the auxotrophic growth enhancing properties of urine extracts. The urine extracts, and pure L-histidine-HCl, were tested using a two-step fluctuation test to estimate auxotrophic growth factor effects in this type of test. Because of a strong dilution effect when adding the histidine-free selection medium, the fluctuation test employed in this study was not found to be particularly sensitive to growth factors. The results of this study indicate that use of a bioassay, employing the same indicator bacteria as the mutagenicity test themselves, is a reliable way to measure histidine-related growth factors in biological samples.(ABSTRACT TRUNCATED AT 400 WORDS)

Enzymes

Placental protein 14 in human in-vitro fertilization early pregnancies.

Placental protein 14 (PP14) and human chorionic gonadotrophin (HCG) were analysed in patients participating in an in-vitro fertilization-embryo transfer programme which did not include any kind of luteal support. Women with normal pregnancies, spontaneous abortions, ectopic pregnancies, biochemical pregnancies and non-pregnant women were compared. A combination of HCG and PP14 analyses distinguished between normal and abnormal implantation as early as 15 days after oocyte retrieval. The product of HCG (IU/l) and PP14 (micrograms/l) concentrations differed significantly between normal pregnancy, spontaneous abortion and ectopic pregnancy (P = 0.0248). It is concluded that both endometrial (PP14) and trophoblastic (HCG) markers, when used in combination, exhibit changes in abnormal implantation which may be clinically useful.

Abortion, Spontaneous

Androstenedione as a predictor of ovarian hyperstimulation syndrome.

Serum concentrations of testosterone, 4-androstene-3,17-dione (androstenedione), dehydroepiandrosterone (DHA) and its sulphate and sex hormone-binding globulin (SHBG) were measured in 30 ovulatory women before and after down-regulation with gonadotrophin releasing-hormone analogue, prior to ovarian stimulation in a programme of in-vitro fertilization and embryo transfer. Nine of the women developed ovarian hyperstimulation syndrome (OHSS) while the others did not. Pretreatment values of androstenedione and the androstenedione:DHA ratios were higher and the testosterone:androstenedione ratios lower in the OHSS women. The decrease in androstenedione levels during down-regulation was greater and the absolute levels following down-regulation were lower in the OHSS group. Higher levels of SHBG and lower testosterone:SHBG ratios, an index of biologically active testosterone, were observed in the OHSS group. The isolated elevation in pretreatment androstenedione levels and the high SHBG levels make the OHSS group different from patients with polycystic ovarian disease. Pretreatment values of testosterone:androstenedione or testosterone/SHBG:androstenedione ratios and/or the decrease in androstenedione during down-regulation may be used as markers, prior to stimulation, for identifying women at risk of developing OHSS.

Adult

Atrial natriuretic peptide concentrations and hemodynamic effects of acute plasma volume expansion in normal pregnancy and preeclampsia.

Plasma atrial natriuretic peptide (ANP) and circulatory responses were studied during rapid plasma volume expansion with crystalloid solutions. Sixteen women with preeclampsia and 16 healthy controls in the third trimester were compared. Basal mean (+/- standard error of the mean) ANP levels were not significantly higher in the preeclamptics than in controls (13.6 +/- 3.5 versus 6.4 +/- 1.1 pmol/L; not significant), but the increment following volume expansion was more pronounced (12.9 +/- 2.6 versus 6.1 +/- 2.3 pmol/L; P less than .05). The mean plasma volume expansion was less in the preeclamptic group (6.1 +/- 0.8 versus 9.3 +/- 1.1%; P less than .05), reflecting a higher capillary permeability in this disease. Left ventricular posterior-wall thickness in diastole was increased in the preeclamptics under basal conditions as compared with the controls (9.8 +/- 0.3 versus 8.9 +/- 0.3 mm; P less than .05), as was the thickness of the interventricular septum in systole (14.3 +/- 0.5 versus 12.3 +/- 0.6 mm; P less than .05). Systemic vascular resistance was higher in the preeclamptic group (19.7 +/- 0.8 versus 15.1 +/- 1.1 peripheral resistance units; P less than .01). In the controls, cardiac output increased by 23 +/- 4% and systemic vascular resistance decreased by 17 +/- 3%. The preeclamptic women reacted in a similar way. Our results indicate that preeclampsia is associated with an enhanced ANP response despite a less pronounced increase in plasma volume during acute fluid challenge.

Adult

Biosynthesis of heparin. Purification of a 110-kDa mouse mastocytoma protein required for both glucosaminyl N-deacetylation and N-sulfation.

The polymer modification process in the biosynthesis of heparin/heparan sulfate is initiated by N-deacetylation, followed by N-sulfation, of N-acetylglucosamine units. Chromatography of a detergent extract from mouse mastocytoma on wheat germ agglutinin-Sepharose yielded a protein fraction, eluted with 0.3 M N-acetylglucosamine, that expressed N-deacetylase activity, but only after recombination with proteins that did not bind to the lectin column. In subsequent purification of the active lectin-bound component, all assays were performed following addition of the unbound protein fraction. After two additional chromatography steps, on blue Sepharose and 3',5'-ADP-agarose, the lectin-binding N-deacetylase component had been purified about 4300-fold with an 11% yield and showed essentially a single band, corresponding to an apparent molecular weight of approximately 110,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of the purified 110-kDa protein showed that it contained, in addition to the N-deacetylase, N-sulfotransferase activity; however, the expression of N-sulfotransferase activity was independent of additional proteins. Backtracking the N-sulfotransferase through the purification scheme previously applied to the N-deacetylase showed the two enzyme activities to the N-deacetylase showed the two enzyme activities to be cofractionated in each separation step. It is proposed that the expression of glucosaminyl N-deacetylase activity depends on the concerted action of (at least) two protein components, one of which also possesses glucosaminyl N-sulfotransferase activity.

Amidohydrolases

Sex hormone-binding globulin, oestradiol-17 beta, progesterone and testosterone at stimulation and after embryo transfer during in-vitro fertilization.

Serum concentrations of sex hormone-binding globulin (SHBG), oestradiol-17 beta progesterone and testosterone were measured in 23 gonadotrophin-stimulated menstrual cycles and in the implantation period [days 11-19 after human chorionic gonadotrophin (HCG) injection] following in-vitro fertilization and embryo transfer. Nine cycles resulted in successful pregnancies, one pregnancy ended in spontaneous abortion (week 14) and 13 cycles were without conception. SHBG levels were significantly elevated above pretreatment values from day 3 after HCG injection onwards. A significant positive correlation was found between increments in SHBG (delta SHBG) during the luteal phase and oestradiol/testosterone ratios during the follicular and luteal phases. In the pregnant cycles a significant positive correlation was also found between delta SHBG during the implantation period and oestradiol/testosterone ratios during the luteal phase and the implantation period. Significant negative correlations were found between delta SHBG and testosterone during the luteal phase in pregnant and non-pregnant women as well as between delta SHBG during the period corresponding to implantation and testosterone during the luteal phase in non-pregnant cycles. The results may reflect a modulating action of the oestrogen/androgen balance upon SHBG levels in subjects with supraphysiological oestradiol levels, such as in stimulated cycles and in very early pregnancy.

Adult

Sperm count and motility influence the results of human fertilization in vitro.

In order to select sperm characteristics that can predict the outcome of in-vitro fertilization-embryo transfer (IVF-ET), semen samples delivered in conjunction with this treatment were studied carefully. We have analysed these data retrospectively in relation to the outcome of treatment. Ninety-one couples were treated for tubal infertility by IVF-ET. Fifteen women became pregnant. Sperm were isolated from semen using a swim-up technique and in most cases 40-80 x 10(3) (range 20-120 x 10(3)) motile sperm per ovum were used for insemination. The couples were divided into three groups: group A who achieved pregnancies, group B who achieved cleaved ova but no pregnancies, and group C who achieved no ova that were cleaved 48 h after oocyte recovery. Comparisons between these groups showed that some characteristics of the native semen samples and the swim-up preparations were significantly different: the sperm concentration (P = 0.001) and total sperm count (P = 0.003) in the native sample, the number of sperm recovered during 30 min of swim-up (P = 0.001), and the specific progressive motility of sperm in the swim-up preparation, both at the time of insemination and on each day, up to 5 days thereafter (P = 0.002-0.028). No pregnancy was achieved with a sperm concentration below 26 x 10(6) ml-1 in the native sample. Some of the sperm characteristics studied in this paper may be of value in the pretreatment evaluation for IVF treatment.

Adult

Nordic in vitro fertilization embryo transfer (IVF/ET) treatment outcomes 1982-1989.

In the four Nordic countries, Denmark, Finland, Norway and Sweden, data were compiled from altogether 30 in vitro fertilization (IVF) clinics regarding their treatment outcomes. Two small, recently established IVF clinics in Finland did not respond to the postal inquiry used for data collection. For each clinic, data were collected from the time they commenced activities until June 1989. Preliminary data for the latter half of 1989 was also gathered. The first IVF-baby in this data set was born in Gothenburg in 1982. Seven years later, in December 1989, altogether 35 clinics in the four countries were in operation and 1,290 children had been born. The largest number of clinics, 12, was to be found in Sweden but the number of treatment cycles in relation to the population was highest in Norway with about 340 treatments per million inhabitants annually during 1988-89, with Sweden in second place: 190 treatments per million inhabitants. The ratio of private to public clinics was highest in Finland, where four out of ten clinics were privately run. A mean clinical pregnancy rate per embryo transfer of 20% was recorded and 85% were singleton pregnancies. Spontaneous abortions occurred in 25% and the ectopic pregnancy rate was 7% of all clinical pregnancies. The 'take home baby rate' for 1988-89 was 13% per embryo transfer. There were no major differences between the four countries.

Embryo Transfer

Isradipine, a new calcium antagonist: effects on maternal and fetal hemodynamics.

To assess the effect of isradipine on blood pressure, and uteroplacental and fetal blood flows in pregnancy-induced hypertension, 41 women with a diastolic blood pressure greater than or equal to 95 mm Hg were included in our study. Of these, 27 received isradipine 5 mg twice daily. Uteroplacental blood flow index was calculated from the activity-time curve of the very low radiation from the placenta after intravenous injection of 18.5 MBq indium-113m. Blood flow velocity was measured in the uterine and umbilical arteries, and fetal aorta, using the pulsed Doppler technique. Investigations were performed before and after 1 week of isradipine. A control group of 14 women was examined in the same way. The isradipine group showed a significant reduction in mean arterial pressure (from 117 to 112 mm Hg) whereas there was no change in the controls. Uteroplacental blood flow indices were similar before treatment in both groups and did not change during treatment. Furthermore, the pulsatility indices were the same in both groups at the first examination and also did not change. Isradipine had no adverse effects on the fetus. In conclusion, isradipine lowered blood pressure without altering uteroplacental or fetal blood flows.

Adult

The early luteal phase in successful and unsuccessful implantation after IVF-ET.

The hormonal milieu at embryo implantation after in-vitro fertilization was investigated. Superstimulation was accomplished with clomiphene citrate and human menopausal gonadotrophin (HMG) injections followed by ovulation induction with human chorionic gonadotrophin (HCG). Venous blood samples were drawn on days 2 and 8, the day of oocyte recovery being day 0. Fifteen women with successful implantation, defined as an ultrasound-verified pregnancy, were compared to 42 women with unsuccessful implantation, using a three-way analysis of variance. Oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) did not differ between the two groups. However, the ratios of oestradiol/progesterone and of testosterone/SHBG were significantly higher in the non-fertile cycles, both on day 2 and on day 8 (P less than 0.05). Furthermore, there was a highly significant decrease in oestradiol, progesterone and testosterone between days 2 and 8 in fertile as well as in non-fertile cycles (P less than 0.001) and a highly significant increase in SHBG from day 2 to day 8 in both groups (P less than 0.001). The higher testosterone/SHBG ratio in the non-pregnant women implies a relative hyperandrogenicity in this group that might have adversely affected the uterine receptivity.

Analysis of Variance

ATP and ADP in human pre-embryos.

Spare human oocytes and pre-embryos from an in-vitro fertilization (IVF) programme were individually analysed for ATP and ADP content using a bioluminescence method employing the firefly luciferin-luciferase reaction. The ATP content of oocytes that failed to fertilize in vitro was 1.71 +/- 0.28 pmol (n = 10), pronuclear stage ova 1.93 +/- 0.08 (n = 6), 2-cell stage 1.78 +/- 0.20 (n = 7), 4-cell stage 1.73 +/- 0.15 (n = 6), 6-8 cell stage 2.76 +/- 0.53 (n = 8), morula stage 2.36 +/- 0.68 (n = 8), early blastocyst stage 2.08 +/- 0.25 (n = 7) and expanded blastocyst stage 2.26 +/- 0.15 (n = 3) pmol. The ADP content of these pre-embryos was low in all stages with a small increment in the 2-4 cell stages and the blastocyst stage. This gave an elevated ATP/ADP ratio (range 19-92) indicating a good energy status. The sensitive luciferin-luciferase assay may be a tool for studying the energy status of spare oocytes and pre-embryos under different incubation conditions in human IVF programmes.

Adenosine Diphosphate

Uteroplacental blood flow measured by placental scintigraphy during epidural anaesthesia for caesarean section.

The uteroplacental blood flow was measured before and during epidural anaesthesia for caesarean section in 11 women. The blood flow was measured with dynamic placental scintigraphy. After an i.v. injection of indium-113m chloride, the gamma radiation over the placenta was recorded with a computer-linked scintillation camera. The uteroplacental blood flow could be calculated from the isotope accumulation curve. The anaesthesia was performed with bupivacaine plain 0.5%, 18-22 ml and a preload of a balanced electrolyte solution 10 ml/kg b.w. was given. The placental blood flow decreased in eight patients and increased in three with a median change of -21%, not being statistically significant. No correlation between maternal blood pressure and placental blood flow was found.

Adult

The effect on uteroplacental blood flow of epidural anaesthesia containing adrenaline for caesarean section.

The effect on uteroplacental blood flow of an epidural anaesthesia containing adrenaline for caesarean section was investigated in ten healthy women using dynamic placental scintigraphy with indium-113m and a computer-linked gamma camera. The epidural anaesthesia was performed with 18-22 ml bupivacaine 5 mg/ml with adrenaline 2.5 micrograms/ml followed by an i.v. balanced electrolyte infusion of 10 ml/kg b.w. A significant median decrease in the total maternal placental blood flow of 34% was found (P less than 0.01). There was also a significant decrease in maternal mean blood pressure of 3 mmHg (0.4 kPa) (P less than 0.05) and a significant negative correlation between the change in maternal blood pressure and the change in uteroplacental blood flow (r = -0.69, P less than 0.05).

Adult

Short-term maximal electrical stimulation--a conservative treatment of urinary incontinence.

Seventeen women with stress and 20 with motor-urge urinary incontinence were treated ambulatorily with short-term maximal electrical stimulation. The duration of the treatment was 20 min daily for 12 weeks. According to the patients' subjective evaluation, two thirds were improved. A markedly diminished leakage of urine (greater than 50% by use of pad test) was found in 6 out of 17 women with stress, and in 13 out of 20 women with motor-urge urinary incontinence. There were no significant differences observed in urodynamic parameters between the registrations performed before and after the present electrical stimulation therapy.

Adult