Serum progesterone at the time of human chorionic gonadotrophin does not predict pregnancy in in-vitro fertilization and embryo transfer

Controversy exists as to whether the serum concentration ofprogesterone on the day of human chorionic gonadotrophin (HCG)administration following ovarian stimulation for in-vitro fertilization(IVF) and embryo transfer can be used to predict the likelihoodof success. This retrospective study was undertaken to answerthis question by analysing a large population of IVF and embryotransfer cycles (n = 756). In addition to the concentrationof progesterone on the day of HCG administration, all variablesknown to impact on IVF and embryo transfer success (such aspatient age), indication for IVF and embryo transfer, numberof oocytes retrieved and the number of embryos generated andtransferred were examined. There was a significant increasein the number of oocytes retrieved with increasing progesteroneconcentration at the time of HCG administration. However, therewas no correlation of progesterone concentration at HCG administrationwith pregnancy and implantation rates. It is concluded thatprevious reports associating a slight elevation of progesteronein gonadotrophin- releasing hormone agonist ovarian stimulationcycles for IVF and embryo transfer may be misleading becauseof a small sample size or the presence of confounding variablesthat affect IVF and embryo transfer success.     

Construction of cosmid contigs and high-resolution restriction mapping of the Huntington disease region of human chromosome 4

The gene responsible for Huntington disease (HD) has been localizedto a 2.2 million base pair (Mbp) region between the loci D4S10and D4S98 on the short arm of human chromosome 4. As part ofa strategy originally designed to clone the gene based on itschromosomal location, we and others previously identified overlappingyeast artificial chromosome (YAC) clones covering most of thisregion. While these YAC clones were useful for initially obtaininglong-range clone continuity, a number of features of the YACsindicated that smaller clones are generally more useful in thesubsequent steps of the positional cloning strategy. In thispaper, we use these YAC clones to generate sets of overlappingcosmid clones covering most of the HD region. We Isolated alarge number of cosmids by screening a chromosome 4-specificcosmld library with labeled DNA from a minimal overlapping setof YAC clones. These cosmid clones were further analyzed byrestriction mapping and hybridization experiments, leading tothe assembly of 185 cosmids Into eleven contigs covering morethan 1.65 Mbp and to a fine-structure restriction map of theregion. Nine of these contigs cover 90 percent of the 1.7 Mbpsubregion between loci D4S125 and D4S98 where the HD gene isnow known to lie. The detailed restriction map and the cosmidclones should facilitate the identification and localizationof cDNAs and polymorphic markers, and they provide reagentsfor large scale DNA sequencing of this region of the human genome.Our results suggest that this strategy should be generally usefulfor converting YAC clones into cosmid contigs and generatinghigh-resolution restriction maps of genomioc regions of interest.     

Parasite-susceptibility phenotypes of F1 Biomphalaria glabrataprogeny derived from interbreeding Schistosoma mansoni-resistant and -susceptible snails

In an effort to investigate the 'flow' of parasite-resistance genes through laboratory snail populations, we determined the susceptibility of progeny snails from freely interbreeding parasite-susceptible and parasite-resistant parents. Five parental populations of Biomphalaria glabrata were used to generate the progeny snails. Three of them contained different proportions of Schistosoma mansoni-susceptible albino snails (NMRI stock) and S. mansoni-resistant pigmented snails (BS-90), while single stock controls comprised the other two parental populations. F(1) snails from each parental population were exposed to S. mansoni miracidia. Some of the progeny snails were exposed as juveniles, others as adults. According to Hardy-Weinberg principle predictions, the F(1) generation from the three pigmented/albino parental populations displayed higher than expected numbers of pigmented (resistant) snails and lower than expected numbers of albino (susceptible) snails. Among the assumptions of the Hardy-Weinberg principle that were not met within these populations could include non-random mating, unequal fecundity, different hatching and survival rates of different genotypes, or other life-history differences between snail stocks. It is clear, though, that for these two laboratory snail stocks there is no fitness cost attached to genetic resistance to the parasite.     

Inclusion of CpG adjuvant with plasmid DNA coding for NcGRA7 improves protection against congenital neosporosis

The present study showed that incorporation of CpG adjuvant into plasmid DNA coding for NcGRA7 antigen resulted in a twofold increase in the level of protection against congenital transfer of Neospora caninum. The level of protection was considerably higher than that observed in pups born from dams immunized with nonrecombinant plasmid.     

Quantitation of hepatitis B viral DNA by solution hybridization: Comparison with DNA polymerase and hepatitis B e antigen during antiviral therapy

Serological markers of hepatitis B virus (HBV) replication were assessed in a randomized, controlled trial of prednisone withdrawal followed by α -interferon in the treatment of chronic hepatitis B. HBV DNA levels in more than 700 serial serum samples from 41 patients were determined by a sensitive and quantitative solution hybridization assay. Results were compared with HBV DNA polymerase (DNAp) activity and hepatitis B e antigen (HBeAg) in 21 untreated controls and 20 treated patients. Among treated patients, the mean pretherapy HBV DNA values were higher in nonresponders than in responders. During prednisone treatment, DNA levels increased an average of 2.1-fold in responders and 1.4-fold in nonresponders. During the 2-week rest interval between prednisone and interferon, DNA values fell an average of 57% in responders. In contrast, the mean DNA values in nonresponders did not change during the same interval. This early distinction between responders and nonresponders was not apparent from DNAp or HBeAg results. During interferon treatment, HBV DNA became undetectable in responders and remained negative during a 1-year follow-up. DNA in nonresponders declined to 14% of baseline during interferon treatment but increased to pretherapy levels after treatment. DNAp values generally paralleled HBV DNA values, but DNAp activity showed more variability and lower sensitivity than did the hybridization assay results. HBeAg values varied independently of HBV DNA and DNAp with a much delayed decline in responders. These results indicate that HBV DNA, when measured quantitatively by a sensitive solution hybridization assay, is an early predictor of the effects of antiviral agents on replication.     

Rapid array-based genomic characterization of a subtle structural abnormality: a patient with psychosis and der(18)t(5;18)(p14.1;p11.23)

Array-based copy number analysis has recently emerged as a rapid means of mapping complex and/or subtle chromosomal abnormalities. We have compared two such techniques, using bacterial artificial chromosome (BAC) and single nucleotide polymorphism (SNP) arrays in the evaluation of a 45-year-old woman with dysmorphic features, mental retardation, psychosis, and an unbalanced derivative chromosome 18, (46,XX, der(18)t(18;?)(p12;?)). Both array-based methods demonstrated that the additional material on chromosome 18 was of 5p origin. The 5p duplication mapped telomeric to 25.320 Mb (BAC array) and 25.607 Mb (SNP array), corresponding to the band 5p14.1. Both BAC and SNP arrays also showed a deletion involving chromosome 18p extending telomeric from 8.437 Mb (BAC array) and 8.352 Mb (SNP array), corresponding to the band 18p11.23. Molecular cytogenetic mapping using fluorescence in situ hybridization (FISH) supported the array findings and further refined the breakpoint regions, confirming that the BAC and SNP chips were both useful in this regard. Both case reports and linkage analyses have implicated these chromosomal intervals in psychosis. The array-based experiments were completed over the course of several days. While these methods do not eliminate the requirement for traditional fine-mapping, they provide an efficient approach to identifying the origin and extent of deleted and duplicated material in chromosomal rearrangements.     

Breast cancer risk associated with ovulation-stimulating drugs

BACKGROUND: Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility. METHODS: A retrospective cohort study of 12,193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors. RESULTS: Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after > or = 20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5). CONCLUSIONS: Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored.     

Apparently changing patterns of inheritance in Alport's hereditary nephritis: Genetic heterogeneity versus altered diagnostic criteria

With the use of more stringent diagnostic criteria, it has recently been shown that some large pedigrees of Alport's and non-Alport's hereditary nephritis fit sex-linked dominant inheritance (O'Neill et al. 1978). We have used similar diagnostic criteria and have studied a number of Michigan pedigrees in order to see if this hypothesis would be confirmed. We found one small pedigree which definitely shows male-to-male transmission, while one large pedigree is tentatively compatible with sex-linked dominant inheritance. Many of the other pedigrees suggested male-to-male transmission. This Michigan experience is compared to other published reports and found to be consistent, although a trend of fewer reports of male-to-male transmission is seen. We conclude that genetic heterogeneity of Alport's hereditary nephritis is likely.     

Autosomal trisomy and maternal use of multivitamin supplements

Recent reports suggest that women carrying certain polymorphisms of folate genes associated with suboptimal folate status might be at increased risk for having a child with Down syndrome or other autosomal trisomies, and hypothesized that maternal use of multivitamin supplements might reduce such risk. To evaluate this hypothesis, we examined data from a population-based case-control study, and contrasted cases of Down syndrome, trisomy 18, and trisomy 13, with unaffected controls. Periconceptional multivitamin use, compared to no such use, was associated with an odds ratio (OR) of 0.9 (95% confidence interval [CI], 0.6-1.3) for having a pregnancy affected by an autosomal trisomy. The OR was 0.8 (95% CI, 0.5-1.3) for Down syndrome and 1.4 (95% CI, 0.5-3.6) for trisomies 13 and 18, with little variation by maternal race or age. Periconceptional multivitamin use was not associated with a major reduction in the risk for common autosomal trisomies.     

Oxatomide: Inhibition and stimulation of histamine release from human lung and leucocytes in vitro

Oxatomide is a very potent inhibitor of histamine release induced by anti-1gE and Timothy pollen extract in passively sensitized human lung fragments and that induced by anti-1gE from human leucocytes. Its spectrum of activity is different from sodium cromoglycate-like drugs.In high concentrations oxatomide, like other antihistamines and related structures, induced histamine release from both lung and leucocytes. However, oxatomide induced histamine release far more effectively from sensitized lung than non-sensitized lung.Inhibition of immunologically induced histamine release by oxatomide may play a part in its action as an anti-hay fever and, possibly, an anti-asthmatic drug.