The effect of epidural anesthesia on safety and success of external cephalic version at term.

The purpose of this study was to assess the effect of epidural anesthesia on the success and safety of external cephalic version (ECV) performed at term. A retrospective record review of all pregnant women > 36 wk gestation who had attempts at ECV at Arnold Palmer Hospital for Children and Women between April 2, 1992, and April 30, 1993, was performed. The standard contraindications to ECVs were observed, and the use of tocolytics and lumbar epidural anesthesia was based on personal preference of the patient's physician. Sixty-one patients underwent 69 attempts, with eight patients having two attempts. There were 37 attempts without epidural and 32 with epidural. Four (10%) and 11 (34%) of the no epidural and epidural groups, respectively, were either in labor or had a cervical dilation > 3 cm at the time of the attempt. The other major patient variables likely to affect the success of ECV were not different between the groups, with the exception of a higher percentage of attempts by the housestaff in the epidural group. The success rate was 59% and 24% for the epidural group and no epidural group, respectively (P < 0.05). The incidence of abruptio placentae, fetal bradycardia, low Apgar scores, and low umbilical artery pH was similar. In our patient population, regional anesthesia increased the success rate of ECV and decreased the cesarean delivery rate with no apparent ill effect on perinatal or maternal morbidity or mortality.

The age-dependent proliferation of rat aortic smooth muscle cells is independent of differential splicing of PDGF A-chain mRNA.

Arterial smooth muscle cells (SMC) from old rats proliferate in vivo (after injury) and in vitro more rapidly than smooth muscle cells from young rats. We previously observed that SMC from old rats contained more PDGF-like growth factor activity than did young SMC. We therefore tested the hypothesis that age-related differences in type of PDGF A-chain gene expression might be responsible for the difference in growth factor activity, since PDGF B-chain gene is minimally expressed both in young and old SMC. Specifically we tested if the old SMC predominantly expressed the long form of the A-chain mRNA, leading to autocrine stimulation by cell-associated PDGF AA-homodimers. A partial cDNA for the rat PDGF A-chain was cloned and sequenced; it is highly conserved compared to the human PDGF-A chain and similarly has two forms, a long form containing all exons, which tends to remain cell-associated and a short form lacking exon 6, which tends to be secreted. Different tissues of both young and old animals express different ratios of these two forms of PDGF-A. However, the relative expression of the different mRNA forms does not change with age, suggesting that differential splicing of PDGF-A and accumulation of cell-associated PDGF A-chain does not determine the enhanced growth potential of old rat SMC.

Prothymosin alpha gene in humans: organization of its promoter region and localization to chromosome 2.

A genomic clone encoding prothymosin alpha (gene symbol: PTMA), a nuclear-targeted protein associated with cell proliferation, was isolated and the 5'-regulatory region subcloned and sequenced. Because of previously reported discrepancies between several cDNA clones and a genomic clone for prothymosin alpha, we determined the sequence of the first exon and of a 1.7-kb region 5' to the first exon. The sequence of the genomic clone reported here corresponds to the published cDNA sequences, suggesting that the previously noted discrepancies may be due to genetic polymorphism in this region. In addition, our sequence data extend the known 5'-upstream sequence by an additional 1.5 kb allowing the identification of numerous, potential cis-acting regulatory sites. This 5'-flanking cloned probe permitted us to localize the prothymosin gene to chromosome 2 in humans.

Prothymosin alpha expression occurs during G1 in proliferating B or T lymphocytes.

To gain insight into possible functions for prothymosin alpha in the proliferative cycle of lymphocytes, we examined the kinetics of prothymosin alpha mRNA expression in mitogen stimulated murine lymphocytes. This mRNA increases after mitogen stimulation, peaking in mid G1. This kinetics is compatible with induction of the prothymosin alpha gene by the c-myc protein (Eilers, M., Schirm, S. and Bishop, J.M. (1991) EMBO J., 10, 133-141). Thus, although prothymosin alpha mRNA is found throughout the cell cycle, the elevated expression in G1 may be associated with an increased requirement for prothymosin alpha during the G1/S transition or the S phase of the cell cycle.

Klinefelter's syndrome: an analysis of the origin of the additional sex chromosome using molecular probes.

The results of our study of the origin of the additional X chromosome in 39 males with a 47,XXY chromosome constitution are reported. We used a total of 20 X-linked RFLPs and successfully determined the origin of all 32 patients in whom DNA from both parents was available, and a further 3 in whom DNA was available from the patient and mother only. Males whose additional X chromosome was maternal in origin were further investigated using an X-linked centromere specific probe to determine the cell division at which the error occurred. Our results showed 53% of the non-disjunction to be attributable to pat mei I errors, 34% to mat mei I errors, 9% to mat mei II errors and 3% to a post-zygotic mitotic error. In the great majority of patients resulting from an error of maternal meiosis there was clear evidence of recombination involving the non-disjoined chromosomes, suggesting that absence of recombination is not an important aetiological factor in non-disjunction of the X chromosome in female meiosis. There was no alteration of parental age associated with the paternally derived 47,XXY males but a marked increase in maternal age among the maternally derived 47,XXY males, the increase being associated with mat mei I but not mat mei II errors. The proportion of paternally and maternally derived cases was similar among different ascertainment classes, suggesting that there is no dramatic effect of parental origin of the additional X chromosome on the phenotype of 47,XXY males.

Comparison of cytologic and genetic distances between long arm subtelomeric markers of human autosome 14 suggests uneven distribution of crossing-over.

The analysis of two rodent X human somatic cell hybrids, carrying different inborn translocations of the human chromosome 14 long arm, has permitted us to narrow down the localization of the structural locus for alpha-1-antitrypsin (PI) to band 14q32.1, proximally to the highly polymorphic DNA locus D14S1 which has been localized by previous studies between 14q32.1 and 14q32.2. These data, evaluated in conjunction with other published information, suggest that the D14S1 locus is cytologically equidistant from both the PI locus and the complex locus for the immunoglobulin heavy chains (IGH) but, genetically, it appears much closer to the latter since the recombination frequency reported between the IGH complex and PI is six times greater than that between the IGH complex and D14S1 (lod score peaks respectively at 26% and 4% with narrow fiducial limits). The present report adds further strength to the frequently proposed hypothesis of a nonlinear relationship between cytologic and genetic distances of human genes. The possibility that this phenomenon may be a feature of frequent occurrence throughout the entire human genome is discussed.

Expression of an 86-kilodalton glycoprotein in an idiopathic mammary adenocarcinoma of a BALB/c mouse.

An epithelial cell line (BALB/c-ST) was established from a mammary adenocarcinoma that developed spontaneously in a 20-month-old BALB/c mouse. Like uninfected normal tissues, the cell line was found to contain three endogeneous murine mammary tumor virus (MuMTV) proviruses, but MuMTV particles and antigens were not detected. The cultured cells, after being inoculated subcutaneously, produced tumors in syngeneic mice, and sera from a high percentage of the tumor-bearing mice specifically immunoprecipitated an 86-kilodalton antigen from the extracts of BALB/c-ST cells. This antigen was found to be glycosylated, but whether or not it was exposed to the cell surface could not be demonstrated by cell-surface iodination and immunoprecipitation studies. The 86-kilodalton antigen, a glycoprotein designated gp86, was not detected in immunoprecipitates from extracts of normal mammary cells or from the extracts of GR, C3H, and BALB/cfC3H mammary tumor cells. After being infected in vitro with RIII-derived MuMTV but not with C3H-derived MuMTV, the BALB/c-ST cells appeared to undergo a phenotypic change in that they did not produce tumors in syngeneic mice, and the expression of gp86 was inhibited. Our results indicate that the expression of gp86 in the mammary cells of BALB/c mice is a consequence of neoplastic transformation and that MuMTV infection modulates its expression.

Prostaglandin regulation of murine mammary tumor virus production: a basis for some of the glucocorticoid and prolactin actions on mammary tumor cell cultures.

Hormonal regulation of mouse mammary tumor virus (MuMTV) production has been studied in cell cultures derived from mammary carcinomas of GR mice. The purpose of this study was to define the role of prolactin in dexamethasone-induced MuMTV production and to evaluate the mechanism(s) of action of these hormones. Results of our investigations in vitro establish a central role for prostaglandins, in particular PGF2 alpha. Prolactin treatment up to 1000 ng/ml increased the MuMTV production only slightly when added alone but a maximal stimulatory response was expressed when prolactin was added simultaneously with dexamethasone 2 micrograms/ml. This prolactin-related enhancement of MuMTV production was probably mediated by PGs since it was inhibited by indomethacin, an inhibitor of prostaglandin synthesis. When higher concentrations of indomethacin were used in dexamethasone-treated cultures, MuMTV production, although inhibited, was restored in part by addition of exogeneous PGF2 alpha. PGF2 alpha added alone stimulated the MuMTV production and, in combination with dexamethasone, showed a synergistic effect on stimulation of MuMTV production. Two compounds, PGF2 alpha and TXA2 (measured as TXB2), were produced in significant concentrations by these cultures. These findings suggest that PGF2 alpha exerts a regulating role on production of MuMTV in GR cells and indicate that the actions of both dexamethasone and prolactin are mediated at least in part by prostaglandins.