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P E Young

Publications and source records attributed to P E Young.

13 recordsLinked to original sources
PubMed1992

Dynamics of methyl groups in proteins as studied by proton-detected 13C NMR spectroscopy. Application to the leucine residues of staphylococcal nuclease.

This paper describes the application of recently developed nuclear magnetic resonance (NMR) pulse sequences to obtain information about the internal dynamics of isotopically enriched hydrophobic side chains in proteins. The two-dimensional spectra provided by the pulse sequences enable one to make accurate measurements of nuclear Overhauser effects (NOE) and longitudinal (T1) and transverse (T2) relaxation times of enriched methyl carbons in proteins. Herein, these techniques are used to investigate the internal dynamics of the 11 leucine side chains of staphylococcal nuclease (SNase), a small enzyme having Mr = 16.8K, in the absence and presence of ligands thymidine 3',5'-bisphosphate (pdTp) and Ca2+. We report the synthesis of [5,5'-13C2]leucine, the preparation of SNase containing the labeled leucine, the sequential assignment of the leucine methyl carbons and protons in the liganded and unliganded proteins, and the measurement of the 13C T1, T2, and NOE values for the SNase leucine methyl carbons. Analysis of the relaxation parameters using the formalism of Lipari and Szabo shows that the internal motions of the leucine methyl carbons are characterized by effective correlation times tau f (5-80 ps) and tau s (less than 2 ns). The fast motion is identified with the rapid rotation of the methyl group about the C gamma-C delta bond axis, while the slow motion is associated with reorientation of the C gamma-C delta bond axis itself. The mean squared order parameters associated with the latter motion, Ss2, lie in the range 0.34-0.92. The values of Ss2 correlate reasonably well with the temperature factors of the leucine methyl carbons obtained from the crystal structures, but some are smaller than anticipated on the basis of the fact that nearly all leucine methyl carbons are buried and have temperature factors no larger than that of the leucine backbone atoms. Five leucine residues in liganded SNase and eight in unliganded SNase have values of Ss2 less than 0.71. These order parameters correspond to large amplitude motions (angular excursions of 27-67 degrees) of the C gamma-C delta bond axis. These results indicate that, in solution, the internal motions of the leucine side chains of SNase are significantly larger than suggested by the X-ray structures or by qualitative analysis of NOESY spectra. Comparison of Ss2 values obtained from liganded and unliganded SNase reveals a strong correlation between delta Ss2 and distance between the leucine methyl carbon and the ligands.(ABSTRACT TRUNCATED AT 400 WORDS)

Leucine↗
PubMed1992

Effect of controlled ovarian hyperstimulation on pregnancy rates after intrauterine insemination.

OBJECTIVE: Our objective was to evaluate the effect of controlled ovarian hyperstimulation on pregnancy rates after intrauterine insemination of washed husband's sperm. STUDY DESIGN: In a private practice setting at the Infertility, Gynecology, and Obstetrics Medical Group in San Diego, 79 treatment programs included intrauterine insemination during natural cycles, 195 included clomiphene stimulation, and 53 had human menopausal gonadotropin stimulation. Pregnancy rates and monthly fecundabilities were calculated by life-table analysis and compared by the Z test. RESULTS: By life-table analysis the cumulative probability of pregnancy after intrauterine insemination with no ovulation induction is 21.0% after six cycles with a monthly fecundability of 3.4%. With clomiphene the pregnancy rate is 32.7% with a monthly fecundability of 6.1%, and with human menopausal gonadotropin the pregnancy rate is 60.7% with a monthly fecundability of 13.0%. The human menopausal gonadotropin group had a significantly higher pregnancy rate and monthly fecundability as compared with the other two groups. There were no differences between the no-stimulation and the clomiphene groups. CONCLUSIONS: Human menopausal gonadotropin stimulation results in a significantly higher pregnancy rate and monthly fecundability after intrauterine insemination as compared with no stimulation or clomiphene use.

Female↗
PubMed1991

Dynamic changes in the distribution of cytoplasmic myosin during Drosophila embryogenesis.

Dramatic changes in the localization of conventional non-muscle myosin characterize early embryogenesis in Drosophila melanogaster. During cellularization, myosin is concentrated around the furrow canals that form the leading margin of the plasma membrane as it plunges inward to package each somatic nucleus into a columnar epithelial cell. During gastrulation, there is specific anti-myosin staining at the apical ends of those cells that change shape in regions of invagination. Both of these localizations appear to result from a redistribution of a cortical store of maternal myosin. In the preblastoderm embryo, myosin is localized to the egg cortex, sub-cortical arrays of inclusions, and, diffusely, the yolk-free periplasm. At the syncytial blastoderm stage, myosin is found within cytoskeletal caps associated with the somatic nuclei at the embryonic surface. Following the final syncytial division, these myosin caps give rise to the myosin rings observed during cellularization. These distributions are observed with both whole immune serum and affinity-purified antibodies directed against Drosophila non-muscle myosin heavy chain. They are not detected in embryos stained with anti-Drosophila muscle myosin antiserum or with preimmune serum. Although immunolocalization can only suggest possible function, these myosin localizations and the coincident changes in cell morphology are consistent with a key role for non-muscle myosin in powering cellularization and gastrulation during embryogenesis.

Animals↗
PubMed1979

Prenatal diagnosis of propionic acidemia.

Prenatal diagnosis of a fetus with propionic acidemia has been accomplished by the detection of methylcitrate, a unique metabolite, in the amniotic fluid by liquid partition chromatography and gas chromatography-mass spectrometry. The diagnosis was confirmed by demonstration of deficient activity of propionyl-CoA carboxylase in cells cultured from the amniotic fluid and in fetal tissues. In two subsequent pregnancies, methylcitrate was not present in amniotic fluid. Enzyme assay indicated that one fetus was heterozygous and the other was normal, and healthy infants were born at term. The analysis of organic acids in amniotic fluid permits very rapid prenatal diagnosis, usually within 48 hours after obtaining the fluid. It may provide a general method in conditions in which an unusual metabolite can be identified.

Abortion, Therapeutic↗
PubMed1979

Genetic amniocentesis in multiple pregnancy.

Eleven cases of twin pregnancy presenting for genetic diagnosis in the second trimester are reported. In all 11 cases, a correct chromosomal diagnosis was made on each of the twins. The technique used required only ultrasound and Evan's blue dye for direction of the amniocentesis. Amniography was not performed. The technique used is described in detail, and its advantages over more standard techniques are described.

Amniocentesis↗
PubMed1978

Ligneous cellulitis associated with an IUD.

Many reports have documented serious pelvic infection associated with an IUD. A case of ligneous pelvic cellulitis with cutaneous sinus tract formation, hydronephrosis, and ureteral obstruction in a patient with an IUD is presented. This is an uncommon manifestation of chronic pelvic infection and responded to antibiotics and steroid administration. The origin and treatment of ligneous cellulitis are discussed.

Adult↗
PubMed1977

Fetal exsanguination and other vascular injuries from midtrimester genetic amniocentesis.

A case of fetal exsanguination after midtrimester genetic amniocentesis is reported. Examination of the ration of fetal-to-meternal red cells in the amniotic fluid obtained by amniocentesis for genetic study from 242 consecutive patients, including the reported case, suggests that fetal hemorrhage is relatively common and difficult to avoid during this procedure. It also appears that hemorrhage occurs significantly more oftern when the placenta is located anteriorly. Reasons as to why the accident is rarely fatal are considered, and some recommendations for patient counselling and management are discussed.

Adult↗
PubMed1977

Amniotic fluid androgens and estrogens in midgestation.

Amniotic fluid androgen and estrogen levels associated with 48 male and 72 female fetuses between 14 and 20 weeks of gestation were measured. Amniotic fluid testosterone levels were significantly higher (P less than 0.001) in the male (224 +/- 11 pg/ml) than the female fetuses (39 +/- 2 pg/ml) with no overlap of values. Amniotic fluid androstenedione concentrations were also significantly higher (P less than 0.001) with male (1024 +/- 53 pg/ml) than female fetuses (668 +/- 39 pg/ml), but there was overlap. There was no difference between anmiotic fluid dehydroepiandrosterone levels for the two sexes. Estrone concentrations were slightly but not significantly higher with the male (353 +/- 33 pg/ml) than with female fetuses (331 +/- 28 pg/ml), while estradiol concentrations were significantly higher (P =0.002) with the female (96 +/- 8 pg/ml) than male (64 +/- 4 pg/ml) fetuses. It is interpreted that the higher amniotic fluid testosterone and androstenedione levels for the male fetuses reflect fetal testicular secretion. The significantly higher estradiol concentrations for the female fetuses may reflect early ovarian secretion.

Amniotic Fluid↗
PubMed1976

Amniocentesis for antenatal diagnosis. Review of problems and outcomes in a large series.

The results of amniocentesis for diagnostic genetic studies on 242 patients are presented in detail. These suggest that obtaining fluid free from contaminating red blood cells is important to successful cell culture. The data also suggest that it is technically more difficult to obtain such fluid tham might be expected, despite the use of ultrasonic localization and experienced operators. Nevertheless, 97 per cent of patients who elect to complete antenatal diagnosis will ultimately obtain the information sought, in time to intervene medically if desired. Moreover, the act of obtaining this information is shown to be without significant risk to the ultimate outcome of pregnancy.

Adult↗
PubMed1976

Amniotic fluid testosterone levels in midpregnancy.

Amniotic fluid testosterone levels were measured on specimens obtained between 12 and 25 weeks' gestation from 58 male-fetus and 77 female-fetus pregnancies. For the male fetuses the mean +/- SE amniotic fluid testosterone level of 223 +/- 10 pg/ml was significantly higher (P less than 0.001) than the concentration found for the female fetuses (40 +/- 2 pg/ml). The ranges were 104-424 and 18-82 pg/ml, respectively, for the same fetuses. In the male fetuses the highest mean level was found during the 17th gestational week, but the mean level observed during any 1 week was not significantly differenf from any other week for both sexes. These data are consistent with the concept that amniotic fluid testosterone levels may be a rapid and effective method for establishing fetal sex in utero during midgestation.

Amniotic Fluid↗