Induction of the cytoplasmic 'petite' mutation in pso mutants of Saccharomyces cerevisiae by photoaddition of furocoumarins or by ultraviolet radiation

The induction of the cytoplasmic ‘petite’ mutation(or rho^–) after photoaddition of either 8-methoxypsoralen(8-MOP) or 3-carbethoxypsoralen (3-CPs), after 254 nm u.v. andafter 6-N-hydroxyaminopurine treatment was examined in threepso mutants in comparison to wild-type Saccharomyces cerevisiae.In three pso mutants which are defective in the induction ofnuclear reverse and forward mutations, the photoaddition of8-MOP enhanced the induction of rho^–. This was true forcells in both exponential and stationary phases of growth. Afterphotoaddition of 3-CPs in both growth phases the frequency ofrho^– was enhanced in pso3–1 whereas pso1–1showed the same response as the wild-type. In pso1–1 showedthe same response as the wild-type. In pso2–1 the frequencyof rho^– was reduced. After treatment with 254 nm u.v.in the stationary phase of growth, rho^– induction wasincreased in pso1–1 and pso3–1 cells as comparedto wild-type cells. However, when treated in the exponentialphase of growth all three pso mutants showed reduced rho^–frequency. The data indicate that the defect in the repair offurocoumarins plus light-induced lesions controlled by nucleargenes (pso) interferes to various extents with the fate of mitochondriallesions. The frequency of rho^– mutants induced in thepso mutants by an analogue of adenine, 6-N-hydroxyaminopurine,was similar to that observed in the wild-type strain, suggestingthat this drug may also act at the mitochondrial level as adirect mutagen in yeast.     

The excess in 2-5 mm follicles seen at ovarian ultrasonography is tightly associated to the follicular arrest of the polycystic ovary syndrome

BACKGROUND: We previously hypothesized that the excess of 2–5 mmfollicles seen at ovarian ultrasonography might be involvedin the follicular arrest (FA) of polycystic ovary syndrome (PCOS),independently from the main putative contributors of FA, namelyhyperandrogenism and hyperinsulinism. METHODS: A multivariate statistical analysis was applied retrospectivelyto clinical, biological and ultrasound data that were consecutivelycollected during 5 years in 457 patients with polycystic ovariesand in 188 age-matched non-hyperandrogenic and regularly cyclingcontrols without PCO at ultrasound. RESULTS: Stepwise discriminant analysis indicated that in PCOS the 2–5 mmfollicle number (FN) gave the strongest correlation to severityof the FA, followed by age and then by fasting insulin level.The other variables [waist circumference (WC), 6–9 mmFN, serum testosterone, FSH, LH and ovarian area] were rejectedby the analysis. Multiple linear regression indicated a significantand independent negative relationship between the 2–5and 6–9 mm FN in the PCOS (r = – 0.186, P <0.01) and control groups (r = – 0.281, P < 0.01). InPCOS only, the 6–9 mm FN was negatively and independentlyrelated to the WC (r = – 0.108, P < 0.05). CONCLUSIONS: The size of the 2–5 mm follicle pool is an independentand important contributor to the FA of PCOS. This result couldbe explained by an exaggerated physiological inhibitory effectfrom this pool on the terminal follicle growth. The metabolicderangement of PCOS that also contributes to the FA would actthrough a different mechanism.     

Pregnancy: Activation of protein kinase C is required for oxytocin-induced contractility in human pregnant myometrium

Intracellular mediators regulating the initiation of parturitionare not fully understood. This study was designed to determinethe possible mechanism of oxytocin-induced uterine contractilityduring labour. In-vitro isometric contraction studies were performedwith longitudinal strips of human pregnant myometrium in thepresence and absence of the protein kinase C inhibitors, staurosporineand RO 31–8220, and the tyrosine kinase inhibitor, genistein.Phospholipase D activity was measured by employing the transphosphatidylationreaction. Staurosporine significantly reduced oxytocin-stimulatedcontractile activity with mean activity reduced by >50% followingthe addition of 10^–6M staurosporine (P < 0.01), whileaddition of 10^–5 M resulted in a measured mean contractileactivity of –10% of the control (P < 0.001, n = 5).Similarly, uterine activity was minimal with oxytocin applicationfollowing incubation with RO 31–8220, mean contractileactivity being reduced by -40% by the addition of 10^–7M RO 31–8220 (P < 0.05) and by –87% by the additionof either 10^–6 or 10^–5 M (P < 0.01, n = 3). Conversely,addition of genistein (10^–7 and 10^–6 M) had littleeffect on oxytocin-induced contractions, although at a higherconcentration (10^–5 M) a significant reduction in oxytocin-inducedcontractile activity was observed (P < 0.01). Oxytocin evokedphospholipase D activation in a concentration- and time-dependentmanner in cultured human pregnant myometrial cells (n = 4).These results indicate that activation of protein kinase C andtyrosine kinase are involved in the regulation of oxytocin-mediatedmyometrial contractile activity and that a coupled phospholipaseD/phosphatidate phosphohydrolase pathway may play a role inthe sustained stimulation of myometrial activity during labour.     

Endocrinology: Efficacy of chronic therapy with the gonadotrophin releasing hormone agonist decapeptyl in patients with polycystic ovary syndrome

Our objective was to assess the endocrine and morphologicalresponse of polycystic ovary syndrome (PCOS) in patients receiving6 months of therapy with the long-acting gonadotrophin releasinghormone agonist (GnRH agonist) decapeptyl (3.75 mg monthly injections).Eighteen documented PCOS patients were basally evaluated forhirsutism, gonadotrophin and androgen concentrations and ovarianmorphology using trans-vaginal ultrasonography. Measurementswere repeated at 3 and 6 months. The results (values as x ±SD) showed a significant improvement in hirsutism (Ferrimanscore 11.0 ± 5.9 versus 6.6 ± 2.7, P < 0.01),acne and seborrhoea. A significant post-treatment decrease ingonadotrophins [follicle-stimulating hormone (FSH): 5.8 ±1.8 versus 3.8 ± 1.1 IU/I, P < 0.01; luteinizing hormone(LH): 10.8 ± 8.3 versus 3.4 ± 3.3 IU/1, P <0.01], LH/FSH ratio (1.8 ± 1.1 versus 0.8 ± 0.6,P < 0.01) and androgen concentrations (free testosterone:4.0 ± 1.9 versus 1.9 ± 0.7 pg/ml, P < 0.01,₄-androstenedione: 3.9 ± 1.2 versus 1.9 ± 0.6ng/ml, P < 0.001) was also found, while oestradiol approximatedcastration concentrations (68.4 ± 29.5 versus 29.1 ±6.7 pg/ml, P < 0.001). Finally, mean ovarian volume (19.7± 6.2 versus 10.9 ± 4.6 cm³, P < 0.001), capsulethickness (2.5 ± 0.8 versus 1.9 ± 0.7 mm, P <0.05) and stromal density dropped significantly, as did uterinevolume (34.2 ± 10.5 versus 19.9 ± 8.9 cm3, P <0.01). In conclusion, treatment of our PCOS patients for 6 monthswith the GnRH agonist decapeptyl proved efficient in inducingsignificant clinical, biochemical and ovarian morphologicalimprovement.     

'Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular sperm'

Sir, I have read with great interest the article by Greco et al.,entitled ‘Efficient treatment of infertility due to spermDNA damage by ICSI with testicular spermatozoa’, publishedin the January issue of Human Reproduction. The study shows that DNA fragmentation levels (assessed by theTUNEL test) in testicular sperm from normozoospermic and oligozoospermicmales were significantly lower than those found in ejaculatedsperm from these same males (4.8±3.6 versus 23.6±5.1%,P<0.001). More     

Role of DNA repair by (A)BC excinuclease and Ogt alkyltransferase in the final distribution of LacI-d mutations induced by N-butyl-N-nitrosourea in Escherichia coli

In the absence of nucleotide excision repair, the additionaldeficiency of the DNA alkyltransferase (ATase) encoded by theconstitutive ogt gene of Escherichia coli caused a marked increasein mutation induction by N-butyl-N-nitrosourea (BNU). Irrespectiveof the presence or absence of the Ogt ATase, little mutagenicresponse was detected in Uvr⁺ bacteria in the concentrationrange 0–8 mM BNU, indicating that most premutagenic DNAlesions induced at these concentrations are efficiently recognizedand repaired by the nucleotide excision repair system. Increasedsusceptibility to mutagenesis by BNU was detected in Uvr^–Ogt⁺ bacteria, but the Uvr^– Ogt^– double mutant exhibitedmuch higher sensitivity. These data suggest that the Ogt ATasecan replace to a great extent the repair capacity of the (A)BCexcinuclease. Forward mutations induced by 6 mM BNU within theinitial part of the lacI gene of E.coli were recovered fromUvr⁺ Ogt^–, Uvr^– Ogt⁺ and Uvr^– Ogt^– bacteria.A total of 454 independent mutations were characterized by DNAsequence analysis. The BNU-induced spectra were dominated byG:C     

Melatonin and steroids in human pre-ovulatory follicular fluid: seasonal variations and granulosa cell steroid production

Follicular fluid samples were obtained from the largest pre-ovulatoryfollicle of 120 women undergoing in-vitro fertilization andwere examined for melatonin by enzyme-linked immunosorbent assayand the steroids oestradiol and progesterone by radioimmunoassay.The concentrations (mean ± SE) of melatonin (213.4 ±18.9 pmol/1) and progesterone (20.1 ± 1.1 µmol/l)in follicular fluid during the autumn and winter (dark) monthswere significantly higher than during the spring and summer(light) months, melatonin (138.4 ± 12.5 pmol/1) and progesterone(11.6 ± 0.8 µmol/l). By contrast, oestradiol concentrationswere significantly lower during the dark months than duringthe light months (264.7 ± 44.1 and 661.8 ± 55.1nmol/l respectively). There was a positive correlation betweenfollicular fluid melatonin and progesterone concentrations (r= 0.271, P < 0.05, n = 120) and a negative relationship betweenmelatonin and oestradiol (r = –0.254, P < 0.05, n =120). The effects of melatonin alone and in combination withhuman chorionic gonadotrophin (HCG) or follicle stimulatinghormone (FSH) on steroidogenesis by human granulosa cell culturewere also investigated. Melatonin had minimal effects on oestradiolor progesterone production by granulosa cells. Interestingly,the oestradiol response in culture appeared to be differentaccording to the time of the year when harvested. During thelight period oestradiol production was enhanced. Melatonin alsosynergized with HCG in increasing progesterone production ondays 6 and 7 after treatment during both light and dark periods.FSH stimulated oestradiol production by the cells on day 2 ofculture. Melatonin had no effect on FSH stimulation of oestradiolproduction. The results of this study suggest that melatoninmay be involved in the regulation of steroidogenesis by thehuman ovaries.     

Pregnancy: Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older

We analysed the results of oocyte donation to women of advancedreproductive age (45 years old) and followed their pregnanciesthrough to delivery in order to assess obstetrical outcomes.Patients (n = 162) aged 45–59 years (mean ± SD;47.3 ± 3.4 years) underwent 218 consecutive attemptsto achieve pregnancy. Oocytes (16.2 ± 7.2 per retrieval)were provided by donors 35 years old. Cleaving embryos (8.2± 4.8 zygotes/couple) were transferred trans-cervically(4.5 ± 1.1 per embryo transfer) to recipients prescribedoral micronized oestradiol and intramuscular progesterone. Followingoocyte aspiration there were six instances of non-fertilization(2.8%) and 212 embryo transfers. A total of 103 pregnancieswas established for an overall pregnancy rate (PR) of 48.6%,which included 17 preclinical pregnancies, 12 spontaneous abortions,and 74 delivered pregnancies (clinical PR 40.6%; delivered PR34.9%). Multiple gestations were frequent (n = 29; 39.2% ofpregnancies) and included 20 twins, seven triplets, and twoquadruplets. Two of the triplet and both of the quadruplet pregnanciesunderwent selective reduction to twins. Antenatal complicationsoccurred in 28 women (37.8% of deliveries) and included pretermlabour (n = 9), gestational hypertension (n = 8), gestationaldiabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia(n = 2), HELLP syndrome (n = 2), and fetal growth retardation(n = 2). 48 (64.8%) deliveries were by Caesa-rean section. Thegestational age at delivery for singletons was 383 ±1.3 weeks (range 35–41 weeks), with birth weight 3218± 513 g (range 1870–4775 g); twins 35.9 ±2.0 weeks (range 32–39 weeks), birth weight 2558 ±497 g (range 1700-3450 g); and triplets 33.5 ± 0.7 weeks(range 32-34 weeks), birth weight 1775 ± 190 g (range1550-2100 g). Neonatal complications (4.6% of babies born) includedgrowth retardation (n = 2), trisomy 21 (n = 1), ventricularseptal defect (n = 1), and small bowel obstruction (n = 1).There were no maternal or neonatal deaths. We conclude thatoocyte donation to women of advanced reproductive age is highlysuccessful in establishing pregnancy. However, despite carefulantenatal screening, obstetrical complications are common, oftensecondary to multiple gestation.     

Characterization of the trp5-27 allele used to monitor drug-induced mitotic gene conversion in the Saccharomyces cerevisiae tester strain D7

Mitotic gene conversions, among other recombinagenic events,can play an important role in the multistep process of carcinogenesis.The ability of chemicals to induce such gene conversions caneasily be monitored in the Saccharomyces cerevisiae tester strainYHE2, a derivative of strain D7. For the detection of drug-inducedgene conversions, two mutations in the TRP5 locus are used,trp5–12 and trp5–27. Here we report on the characterizationof the stable allele trp5–27. Our analysis revealed tworelevant mutations in trp5–27: (a) a transition C to Tat position 121 after ATG that results in an amber stop codonand abolishes gene expression and (b) a transversion A to Tat position 1555 that creates an ochre stop codon. Simultaneousamber and ochre suppression with the suppressors SUP3 and SUP11,respectively, was capable of relieving the tryptophan-requiringphenotype of strains carrying the trp5–27 allele. Thesefindings have implications on the length of gene conversiontracts in conversion events between trp5–12 and trp5–27:conversion tracts can cover several kilobases, if the site ofthe mutation in trp5–12 lies outside of the positionsmutated in trp5–27. Conversely, the maximal length islimited to 1435 bp, if the mutation in trp5–12 is locatedbetween the positions mutated in trp5–27. ¹To whom correspondence should be addressed     

Cognitive-behavioral therapy for physical and emotional disturbances in adolescents with polycystic ovary syndrome: a pilot study

Objective To evaluate the feasibility and effectiveness of anenhanced cognitive–behavioral therapy (CBT), Primary andSecondary Control Enhancement Training (PASCET-PI-2), for physical(obesity) and emotional (depression) disturbances in adolescentswith polycystic ovary syndrome (PCOS). Method In anopen trial, 12 adolescents with PCOS, obesity, and depressionunderwent eight weekly sessions and three family-based sessionsof CBT enhanced by lifestyle goals (nutrition and exercise),physical illness narrative (meaning of having PCOS), and familypsychoeducation (family functioning). Results Weightshowed a significant decrease across the eight sessions froman average of 104 kg (SD = 26) to an average of 93 kg (SD =18), t(11) = 6.6, p <.05. Depressive symptoms on the Children'sDepression Inventory significantly decreased from a mean of17 (SD = 3) to a mean of 9.6 (SD = 2), t(11) = 16.8, p <.01. Conclusion Amanual-based CBT approach to treat depression in adolescentswith PCOS and obesity appears to be promising.     

Critical role of dendritic cells in determining the Th1/Th2 balance upon Leishmania major infection

The onset of T_h1 immunity is in part regulated by genetic background.To elucidate the cell type carrying critical factors determiningthe T_h1 response, we employed Rag-2^–/– mice on Leishmaniamajor-susceptible BALB/c and -resistant B10.D2 backgrounds.By using bone marrow (BM) chimeras generated by the transplantationof B10.D2 BM cells into BALB/c-Rag-2^–/– mice, andvice versa, it was shown that hematopoietic cells carry factorsdetermining the disease outcome and T_h1 response against L.major infection. B10.D2-Rag-2^–/– mice reconstitutedwith BALB/c CD4⁺ T cells exhibited a T_h1 response and controlledL. major infection. Wild-type BALB/c mice inoculated with L.major-parasitized B10.D2-Rag-2^–/– splenocytes alsoexhibited a T_h1 response and a mild disease outcome, whereassuch a T_h1 response was not induced when CD11c⁺ dendritic cells(DCs) were depleted from parasitized B10.D2-Rag-2^–/–splenocytes. T_h1 response was reconstituted by the additionof L. major-parasitized B10.D2 DCs but not L. major-parasitizedBALB/c DCs to DC-depleted parasitized B10.D2-Rag-2^–/–splenocytes. These results indicate that DCs determine the outcomeof the disease upon L. major infection.     

Endocrinology: Variability in the immunoreactive and bioactive follicle stimulating hormone content of human urinary menopausal gonadotrophin preparations

The within- and between-batch variation in the immuno-reactiveand in-vitro bioactive FSH content of Pergonal, Metrodin andMetrodin-HP was investigated. Three batches of Pergonal andMetrodin, consisting of three ampoules in each batch, and threebatches of Metrodin-HP, consisting of between one and threeampoules per batch, were selected at random. The follicle stimulatinghormone (FSH) content of Pergonal, Metrodin and Metrodin-HPwas determined by radioimmunoassay (R-FSH) and the in-vitrorat Sertoli cell bioassay (B-FSH) using the international urinarystandard 70/45. The variability in the FSH content of the preparationswas evaluated within and between batches by analysis of variance.Within-batch variability of B-FSH was not observed in Pergonalor Metrodin-HP but was seen in two batches of Metrodin in whichthe potency varied by up to 2.4 fold (P = 0.03). The between-batchR-FSH potencies of Pergonal (P1–P3) varied, with P2 (59.8± 0.6) and P3 (61.7 ± 0.9) being higher than P1(47.1 ± 1.5 mean ± SEM IU/ampoule, P < 0.01).A similar pattern of variability was observed for B-FSH. ForMetrodin, each of the batch R-FSH potencies was dissimilar (P< 0.02), with estimates ranging from 34.9 ± 1.2 to64.3 ± 1.8 IU/ampoule. Furthermore, the extensive within-batchB-FSH variation from two batches confounded any meaningful comparisonof between-batch variability. For Metrodin-HP, there was nobetween-batch B-FSH variation (29.0 ± 6.1 to 33.0 ±0.3 IU/ampoule) and the R-FSH content was also well controlled(41.2 ± 0.5 to 46.9 ± 1.1 IU/ampoule). The B:I(bioassay: immunoassay) FSH ratios of Pergonal (0.9 ±0.1, n = 9), Metrodin (2.2 ± 0.3, n = 9) and Metrodin-HP(0.7 ± 0.04, n = 5) were all dissimilar (P < 0.03).Within- and between-batch variations were observed to varyingdegrees in three human urinary gonadotrophin preparations. Thevariations in B-FSH content between the preparations appearedmore extensive than for R-FSH. Of the preparations studied,Metrodin-HP exhibited the least variability.     

Clinical evidence for an LH ceiling?

Dear Sir, We read with interest the letter by M.Filicori (Filicori etal., 2003) commenting on our pilot studies published earlierin Human Reproduction (Loumaye et al., 2003). Filicori et al. remind us that they have repeatedly reporteda reduction in ‘small’ follicles (<10 mm)by administering LH activity during the follicular phase. Thissupports a ‘ceiling’ for LH on antral follicleswith a diameter <10 mm; however, they challenge sucheffect of LH on larger follicles (>10 mm). This is basedon four pilot studies published by the same     

The effect of smoking and varicocele on human sperm acrosin activity and acrosome reaction

Smoking and varicocele are frequent findings in the medicalhistory and physical examination of patients attending and rologicaloutpatient departments. However, data about their influenceon human semen parameters, such as sperm concentration and motility,are contradictory. Therefore, the purpose of this study wasto examine sperm function (acrosin activity and induction ofthe acrosome reaction) in smokers (n = 130) and varicocele patients(n = 30)compared with normal fertile donors (n = 20). The acrosomereaction was detected by triple staining after 3 h ofincubationat 37°C, followed by treatment with 0.1%dimethyl sulphoxide(spontaneous acrosome reaction) and 10 µM calcium ionophoreA23187 (induced acrosome reaction) for 1 h at 37°C. Acrosinactivity was measured by gelatinolysis. The diameters aroundthe sperm heads after gelatinolysis and the percentages of spermatozoashowinghalo formations were evaluated. The inducibility of theacrosome reaction was significantly lower in semen samples fromsmokers than in those from the fertile group (7.1 ±3.2versus 11.2 ± 4.0%, P < 0.01), whereas no statisticallysignificant difference was demonstrated in spermatozoa frompatients with varicocele (9.3 ± 4.3%). Both the percentagesof spermatozoa with halo formation (53.3 ±20.0 versus76.6 ± 13.6%, P < 0.05) and the halo diameters (16.1± 6.6 versus 31.0 ± 14.5 urn, P < 0.001) weresignificantly lower in the varicocele group than in thesamplesfrom fertile men. These data suggest that smoking and varicoceleaffect sperm function, and that the standard semen parametersalone are insufficient to evaluate the influence of both factorson human male fertility.     

Andrology: The presence of Mullerian inhibiting substance in human seminal plasma

Müllerian inhibiting substance (MIS), produced by testicu-IarSertoli cells, is present in adult male serum. The first aimof this study was to determine if MIS is present in seminalplasma. Using an enzyme-linked immunosorbent assay (ELISA),we measured MIS concentrations in seminal plasma from 23 donorsexhibiting normal (WHO criteria) sperm qualities, and 169 patientswith subnormal sperm parameters. The second aim of this studywas to examine a potential relationship between MIS and spermmotility. MIS concentrations in seminal plasma ranged from 0.5to 3.6 ng/ml in donors and from 0.5 to 17.8 ng/ml in patients.Motility index (MI, mean ± SEM) for all patient sampleswas lower compared with donors (113.3 ± 3.2 and 1983± 13.5, P < 0.00001), while mean MIS concentration(± SEM) was higher (4.2 ± 03 and 1.4 ±0.2, P < 0.0003). When the patients were stratified intoGroups I (motility < 50%, n = 42) and D (motility >50%,n = 127), the MI (mean ± SEM) values were 623 ±3.8 and 130.2 ± 2.7 respectively (P < 0.0001 for bothcompared with donors) and mean MIS concentrations (±SEM) were 5.4 ± 0.6 and 3.9 ± 03, respectively(P < 0.0001 and P < 0.001 compared with donors). The inverserelationship between MIS concentration in seminal plasma andmotility index suggests that MIS may have a function in modulatingmotility.     

Association of early {beta}-human chorionic gonadotrophin values with pregnancy wastage and multiple implantation in a donor oocyte programme

An early marker predictive of a viable pregnancy would easethe anxiety associated with positive pregnancy tests after theuse of donor oocytes. We examined the predictive value of anearly serum quantitative human chorionic gonadotrophin (Q-HCG)concentration on pregnancy outcome following oocyte donation.Embryo transfers after oocyte donation resulting in a positiveserum -HCG were examined beginning 9 days after embryo transferfrom those samples assayed in our laboratory (n = 77). Q-HCGconcentrations were measured in our laboratory by an immunoradiometricassay utilizing the first International Reference Preparation.Implantations were defined as the number of gestational sacsvisualized by transvaginal ultrasound 21 days after embryo transfer.Biochemical pregnancies were those with transient elevationsin -HCG concentration but without implantation sites. Spontaneousabortions were characterized by an implantation site with theeventual arrest of development. Ongoing/delivered pregnanciesdeveloped appropriately and proceeded beyond the first trimester.Day 9 Q-HCG concentrations did not differentiate between biochemicalpregnancies/spontaneous abortions and ongoing/delivered pregnancies,although mean ± SD concentrations for biochemical pregnancieswere significantly lower than those for the other groups (P< 0.0001): biochemical pregnancies, n = 18, 5.8 ±8.9 mlU/ml, range 0–35; spontaneous abortions, n = 2,46.0 ± 10.0 mlU/ml, range 39–53; ongoing/deliveredpregnancies, n = 57, 41.5 ± 35.4 mlU/ml, range 0–214.In addition, day 9 Q-HCG concentrations did not differentiatebetween multiple implantations, although the implantation offour sacs had a significantly higher mean Q-HCG concentrationcompared with the implantation of fewer sacs (P > 0.0001):one sac, n = 22, 32.2 ± 21.5 mlU/ml, range 3–78;two sacs, n = 25, 35.8 ± 21.3, range 0–81; threesacs, n = 7, 47.1 ± 37.1 mlU/ml, range 22–126;four sacs, n = 4, 122.3 ± 62.4 mlU/ml, range 76–214.The positive predictive value of a Q-HCG >10 mlU/ml was 0.91(sensitivity 91%, specificity 75%). These initial data suggestthat early day 9 serum Q-HCG determinations do not accuratelyidentify viable pregnancies or multiple implantations. Evenan early negative pregnancy test should be repeated becauseit can be associated with a normal pregnancy.     

Proinflammatory cytokine polymorphisms and the risk of preterm birth and low birthweight in a Japanese population

Pregnancy and parturition involve a complex and poorly understoodmolecular and biological interplay between mother and fetus.Inflammatory cytokines have been reported to be associated withfetal growth and parturition. The aim of this study was to examinewhether common proinflammatory cytokine polymorphisms are associatedwith preterm birth (PTB), low birthweight or intrauterine growthrestriction in a Japanese population. We assessed a consecutiveseries of 414 women who had singleton deliveries in Sapporo,Japan between 2001 and 2005. Genotyping of IL1A –889C/T,+4845G/T (A114S), IL1B –511C/T, –31C/T, IL2 –384T/Gand IL6 –634C/G polymorphisms was determined by an allelicdiscrimination assay. The risk of PTB significantly increasedin women carrying the IL1A –889T allele (CC genotype [reference];CT genotype, odds ratios (OR): 2.5; 95% confidence intervals(95% CI): 1.4–4.8; CT+TT genotypes [dominant genotypemodel], OR: 2.5, 95% CI: 1.3–4.6). Similarly, the riskof PTB significantly increased in women carrying the IL1A +4845Tallele (GG genotype [reference]; GT genotype, OR: 2.4, 95% CI:1.3–4.4; GT+TT genotypes [dominant genotype model], OR:2.3, 95% CI: 1.2–4.2). The frequency of the IL1A TT haplotypein mothers with PTB was significantly higher than in motherswho had a term birth (P < 0.001), whereas the frequency ofthe IL1A CG haplotype in mothers who had a PTB was significantlylower (P < 0.001). Our findings suggest that the polymorphismsand haplotypes in the IL1A gene are associated with PTB in Japanesewomen.     

Sexual arousal and the quality of semen produced by masturbation

The influence of sexual arousal on the quality of semen producedby masturbation was investigated. One group of 29 patients referredto our andrology outpatient clinic (group A) and one group of14 healthy potential sperm donors filled out a questionnaireafter having produced two semen samples, at least 1 month apart,by masturbation. Changes in questionnaire scores between firstand second visit were compared with changes in semen characteristicsbetween those two occasions to identify statistically significantcorrelations. A second group of 23 subfertility patients (groupB) were asked to produce a semen sample by masturbation in adesignated room at the hospital without additional sexual stimulation,and a second sample while viewing a sexually explicit video.Differences in questionnaire scores and semen characteristicsobtained with visual erotic stimulation (VES) and without VESwere analysed. In group A, the change in sexual arousal andchange in intensity of orgasm correlated with change in semenvolume (r = 038, P < 0.05; r = 0.48, P < 0.01 respectively).In healthy donors and group B, however, no such correlationwas found. With VES in group B, significantly higher scoreswere given for ‘feeling at ease/relaxed’ (P <0.01), ‘sexual arousal’ (P < 0.001), ‘qualityof erection’ (P = 0.01), ‘intensity of orgasm’(P < 0.05), ‘satisfaction after orgasm’ (P <0.05), and ‘ease with which orgasm was achieved’(P < 0.001) with VES compared to without VES. There was nostatistically significant improvement in semen quality withVES compared to without VES. It is concluded that sexual arousalhas no significant influence on the quality of an ejaculateproduced by masturbation. On the other hand, providing a patientwith a sexually stimulating video is obviously a facilitativefactor when the patient ‘has to’ produce a semensample for analysis. The use of visual erotic stimulation isrecommended when patients and donors have to produce a semensample in the uninviting surroundings of a fertility clinic.     

Microsomal metabolism and activation of the environmental carcinogen 2-amino-3-methyl-9H-pyrido[2,3-b]indole

2-Amino–3–methyl–9H–pyrido[2,3–b]indole(MeA