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Biomedical subjects

D Young

Publications and source records attributed to D Young.

At least 217 records · Page 12Linked to original sources
PubMed1997

The effectiveness of sweeping membranes at term: a randomized trial.

OBJECTIVE: To determine whether sweeping or stripping membranes at 38-40 weeks' gestation leads to spontaneous labor within 7 days. METHODS: One hundred fifty antenatal low-risk patients at 38-40 weeks' gestation were assigned randomly to sweeping or control (ie, Bishop score only) groups and stratified based on the ability to pass a finger through the internal os. The primary outcome was the rate of spontaneous labor within 7 days. Major secondary outcomes included the spontaneous labor rate before 41 weeks and the overall spontaneous labor rate. Other outcomes included maternal and neonatal morbidity. The sample size was calculated based on doubling of the spontaneous labor rate within 7 days from 28% to 56% (alpha = 0.05, beta = 0.10). RESULTS: The subjects were demographically similar between the groups. There were no differences between the groups in the primary outcome of spontaneous labor within 7 days (33% sweeping, 38% control; P = .39) or in the secondary outcomes of spontaneous labor before 41 weeks (P = .66) or the overall spontaneous labor rate (P = .09). The Bishop score predicted spontaneous labor within 7 days (P = .003), and gestational age at enrollment predicted spontaneous labor before 41 weeks (P = .008) and the overall spontaneous labor rate (P = .008), using logistic regression to control for potential confounders. CONCLUSIONS: Sweeping membranes once at 38-40 weeks' gestation does not significantly increase the proportion of women who begin spontaneous labor within 7 days.

Adult↗
PubMed1997

Molecular genetic and biochemical analysis of Brassica napus proliferating cell nuclear antigen function.

A cDNA encoding the proliferating cell nuclear antigen (PCNA) from Brassica napus (oilseed rape) was shown to complement the lethal deletion mutation in the PCNA gene (delta POL30) of Saccharomyces cerevisiae. We provide unequivocal evidence that the B. napus PCNA can perform all the essential functions of the yeast PCNA in DNA replication, although some species-specific differences may exist. In addition, the B. napus PCNA expressed as a fusion polypeptide with glutathione S-transferase (GST) was shown to stimulate the activity and processivity of two delta-like DNA polymerases from wheat in vitro. These experiments provide direct biochemical evidence that the B. napus PCNA may function as an auxiliary factor in plant cell DNA replication.

Brassica↗
PubMed1997

Isolation and characterization of the mycobacterial phagosome: segregation from the endosomal/lysosomal pathway.

Mycobacteria have the ability to persist within host phagocytes, and their success as intracellular pathogens is thought to be related to the ability to modify their intracellular environment. After entry into phagocytes, mycobacteria-containing phagosomes acquire markers for the endosomal pathway, but do not fuse with lysosomes. The molecular machinery that is involved in the entry and survival of mycobacteria in host cells is poorly characterized. Here we describe the use of organelle electrophoresis to study the uptake of Mycobacterium bovis bacille Calmette Guerin (BCG) into murine macrophages. We demonstrate that live, but not dead, mycobacteria occupy a phagosome that can be physically separated from endosomal/lysosomal compartments. Biochemical analysis of purified mycobacterial phagosomes revealed the absence of endosomal/lysosomal markers LAMP-1 and beta-hexosaminidase. Combining subcellular fractionation with two-dimensional gel electrophoresis, we found that a set of host proteins was present in phagosomes that were absent from endosomal/lysosomal compartments. The residence of mycobacteria in compartments outside the endosomal/lysosomal system may explain their persistence inside host cells and their sequestration from immune recognition. Furthermore, the approach described here may contribute to an improved understanding of the molecular mechanisms that determine the intracellular fate of mycobacteria during infection.

Animals↗
PubMed1997

Electromagnetic fields enhance chemically-induced hyperploidy in mammalian oocytes.

Epidemiological studies suggest that exposure to electromagnetic fields (EMFs) in the environment may be associated with mutagenic changes, but the relation between EMF exposure and aneuploidy has not previously been studied. Environmental EMFs apparently lack the energy necessary to function as aneugens, but the possibility exists that EMFs could influence the incidence of aneuploidy synergistically because EMFs can activate the neuroendocrine system, and ovulation and oocyte meiotic maturation are under neurohormonal control. This hypothesis was tested by examining the effect of EMF exposure on the occurrence of hyperploidy in mouse oocytes induced by vinblastine sulphate (VBS), which was employed as a surrogate for aneugens in the environment. The incidence of hyperploidy in metaphase II oocytes of individual mice following superovulation was determined, and statistical methods were developed to assess whether EMF exposure during oogenesis in the presence of VBS altered the rate of hyperploidy. A significant effect of EMF exposure on VBS-induced hyperploidy was found (P < 0.05). The data suggested that the EMF primarily affected the mice that exhibited a high incidence of VBS-induced hyperploidy. Exposure had no effect on the number of oocytes ovulated nor on the occurrence of hypoploidy. The results support the hypothesis that EMF exposure can promote the occurrence of aneuploidy caused by an aneugen via a mechanism involving the neuroendocrine system.

Animals↗
PubMed1997

1,2-propanediol-induced premature centromere separation in mouse oocytes and aneuploidy in one-cell zygotes.

Aneuploidy in germ cells results in reproductive failure and mental and physical disorders in humans. Unfortunately, little is known about the causes and mechanisms of aneuploidy induction. The objective of this study was to test the hypothesis that propylene glycol (1,2-propanediol; PG) induces cytogenetic aberrations in mouse metaphase II (MII) oocytes that predispose zygotes to aneuploidy. Female ICR mice received 7.5 IU eCG and 5.0 IU hCG 48 h later. PG doses of 1300, 2600, and 5200 mg/kg body weight were given 3 h post-hCG; controls received the solvent deionized water. Ovulated oocytes were collected 16 h after administration of PG and processed for cytogenetic analysis. For the one-cell zygote cytogenetic study, females were given PG and paired (1:1) with ICR males for 16 h. Females that mated were given 2 x 10(-3) M colchicine 22 h post-PG, and zygotes were collected 18 h later. PG significantly (p < 0.05) increased both the proportion of MII oocytes with premature centromere separation (PCS) and the proportion of aneuploid one-cell zygotes. These results support the hypothesis that PG-induced PCS in MII oocytes predisposes zygotes to aneuploidy.

Aneuploidy↗
PubMed1997

Quantification of neuroreceptors in the living human brain: III. D2-like dopamine receptors: theory, validation, and changes during normal aging.

Dopamine receptor density is believed to decline in normal aging. To test this hypothesis, we measured the density of dopamine D2-like receptors in vivo in the neostriatum of normal living humans by using the graphical method. This method determines the D2-like dopamine receptor density in the human brain with an occupying ligand (unlabeled haloperidol) and a radioligand (labeled 3-N-methylspiperone). The method was examined critically, and the assumptions underlying the method were shown to be valid. The validation included comparison of the representation of tracer metabolism by high-pressure liquid chromatography and model assays, calculation of the lumped constant Dw from the value of its components, and comparable tracer partition coefficients in vitro and in vivo. In error analysis, the method consistently performed as well as the direct least-squares regression at statistical noise levels appropriate for the tomograph used in these studies. The method revealed that the density of the D2-like receptors that bind haloperidol in the caudate nucleus of normal humans declined 1% per year after the age of 18 years.

Aging↗
PubMed1997

Elevated levels of serum nitrate, a stable end product of nitric oxide, in women with pre-eclampsia.

OBJECTIVES: Nitric oxide released from vascular endothelial cells is a potent vasodilator and inhibits platelet adhesion. It has been suggested that decreased nitric oxide production from dysfunctional endothelial cells is implicated in the pathophysiology of pre-eclampsia. In this study evidence was sought for abnormal production of nitric oxide in pre-eclamptic women. PARTICIPANTS: Blood was collected from 20 women presenting with pre-eclampsia, from 20 matched healthy pregnant controls and from 12 nonpregnant women of childbearing age. METHODS: Serum nitrate, the stable end metabolite of nitric oxide, was measured by vanadium III chloride reduction and chemiluminescence. RESULTS: Sera from women with pre-eclampsia had significantly higher nitrate concentrations (mean 47.4 mumol/L [SD 13.6]) compared with healthy pregnant (mean 31.2 mumol/L [SD 9.14]) and nonpregnant (mean 32.1 mumol/L [SD 10.0]) controls. CONCLUSIONS: These results do not support the hypothesis that decreased endothelial cell nitric oxide production may be important in the pathophysiology of pre-eclampsia. On the contrary, serum nitrate levels are increased which may reflect either increased production of nitric oxide from an unidentified source or decreased elimination through the kidneys.

Adult↗
PubMed1997

Mkh1, a MEK kinase required for cell wall integrity and proper response to osmotic and temperature stress in Schizosaccharomyces pombe.

We have identified a Schizosaccharomyces pombe gene, mkh1, that encodes a MEK kinase (MEKK) homolog. The coding region of mkh1 is contained within a single exon encoding a 1,116-amino-acid protein. The putative catalytic domain of Mkh1 is 54% identical to the catalytic domain of S. cerevisiae Bck1, the most closely related protein. Deletion of mkh1 did not significantly affect cell growth or division under standard conditions. However, mkh1delta cell growth was inhibited by high KCl or NaCl concentrations. mkh1delta cells required a longer time to reenter the cell cycle after prolonged stationary-phase arrest. Also, mkh1delta cells exhibited a round cell shape, while overexpression of Mkh1 resulted in an elongated cell shape. mkh1delta cells exhibited a more dramatic phenotype when grown in nutrient-limiting conditions at high temperature or in hyperosmotic medium. In such conditions, completion of cytokinesis was inhibited, resulting in the growth of pseudohyphal filaments with multiple septa and nuclei. Also, mkh1delta cells were hypersensitive to beta-glucanase treatment. Together these results suggest that Mkh1 regulates cell morphology, cell wall integrity, salt resistance, cell cycle reentry from stationary-phase arrest, and filamentous growth in response to stress. These phenotypes are essentially identical to those exhibited by cells lacking Pmk1/Spm1, a recently identified mitogen-activated protein kinase. Our evidence suggests that Pmk1/Spm1 acts downstream from Mkh1 in a common pathway. Our results also suggest that Mkh1 and Pck2 act independently to maintain cell wall integrity, cell morphology, and salt resistance but act in opposition to regulate filamentous growth.

Amino Acid Sequence↗
PubMed1997

Hospital based primary care clinics. Complementary to general practice.

OBJECTIVE: To describe the patients attending a hospital based primary care clinic (HBPCC) focusing on the main medical and non-medical reasons for their seeking health care at the clinic, and their expectations of, and satisfaction with the care. METHODS: The study was set in a HBPCC in the northern region of metropolitan Melbourne, Australia. Bilingual interviewers assisted consecutive new patients to complete a pre- and post-consultation questionnaire seeking information on the presenting complaint, patient-reported reason for encounter (RFE), doctor-recorded health problem, treatments received, and patient expectations of and satisfaction with care. RESULTS: The sample (n = 197) was young (mean age 33 years). A high proportion came from a low socioeconomic group (68%) and there was a higher than expected proportion of patients with a non-English speaking background (NESB) (53%). Three-quarters had a regular GP elsewhere. Important reasons for choosing this service were accessibility and familiarity: being part of a hospital: case of obtaining radiological examinations, and the quality of the doctors. The commonest health problem was trauma related (14-16%). The main body systems involved were locomotor, skin, digestive, respiratory, pregnancy related and non specific. Patients were mostly satisfied with their cares those with ill-defined problems were more likely to report that their expectation were not completely met. There were no significant demographic and ethnic variations in the outcome variables. CONCLUSION: HBPCCs can complement the GP's ongoing relationship with patients from NESB and lower socioeconomic groups to improve the continuity and coordination of healthcare. Experienced and culturally sensitive GPs, good communications, and an effective and comprehensive interpreter service are necessary to facilitate this care coordination. One strategy is a hospital based department of general practice linking academic GPs and a local divisional network of GPs, to provide this clinical service and undertake teaching and research in the areas highlighted by this study.

Adult↗
PubMed1997

Molecular analysis of mutations in T-lymphocytes from experienced Soviet cosmonauts.

Somatic mutation in five cosmonauts who have completed spaceflights of 7 to 365 days was analyzed using the clonal HPRT assay. The doses received in space by the cosmonauts ranged from 4 to 127 mGy. hprt mutant frequencies were 2.4-5.0-fold higher than age-corrected values established for healthy, unexposed subjects in western countries [Tates et al. (1991): Mutat Res 253: 199-213; Branda et al. (1993): Mutat Res 285: 267-279] and 2- to 3-fold higher than those determined for unexposed individuals residing in Russia [Jones et al. (1995): Mutat Res 338: 129-139]. A total of 107 collected mutant clones were analyzed by multiplex PCR. No excess of deletions was detected and their frequency did not correlate with either accumulated dose or the age of the cosmonauts. In 62 mutants cDNA was isolated by RT-PCR and sequenced. Those with splicing errors, as well as the mutants that did not produce cDNA, were further analyzed by the sequencing of exon(s)-containing fragments amplified from genomic DNA. The mutational spectrum recovered from the cosmonauts differed substantially from that of unexposed healthy subjects (P = 0.042), and exhibited an increased incidence of splicing errors, frameshifts, and complex mutations. Higher frequencies of contribution of AT-->GC transitions and GC-->TA transversions were also observed. The increased mutant frequencies and observed shifts in mutational spectra likely indicate a combination of potential influences, including environment, lifestyle, and occupational exposures. Further elucidation of these potential influences will require a more extensive study involving the general population sharing similar environment, cosmonauts in training and cosmonauts participating in space flights.

Adult↗
PubMed1996

Expression of human MutS homolog 2 (hMSH2) protein in resting and proliferating cells.

The hMSH2 protein plays an important role in the DNA mismatch repair system. Since this system is involved in the correction of errors that occur during DNA replication, we studied the expression of hMSH2 protein in resting and DNA-replicating cells, as well as through the cell cycle in cell types with different growth characteristics. Using Western blot analysis, we showed that hMSH2 protein was detectable in resting peripheral blood lymphocytes and thymocytes. However, when these cells were induced to proliferate, the protein level increased at least 12-fold. In cell-cycle dependent expression studies we chose two DNA mismatch repair proficient cell lines (HEL and HeLa-S3), and flow cytometry was used to monitor cell-cycle progression. At every phase in the cell cycle, the steady-state level of hMSH2 was higher than in resting lymphocytes or thymocytes, and only minor variations of expression level were observed through the cell cycle. In particular, a two to fourfold decrease in hMSH2 expression occurred at G1 in HEL and at early S phase in HeLa-S3, but higher expression levels resumed during the replicative and postreplicative phases of the cell cycle. Interestingly, hMSH2 protein expression decreased fourfold when HEL cells were induced to differentiate along the megakaryocyte lineage, when continuous DNA replication occurs without mitosis. These results suggest that a basal level of hMSH2 protein expression is necessary for resting and differentiated cells, and that increased hMSH2 protein expression is required when DNA replication is activated and followed by mitosis.

Cell Cycle↗
PubMed1996

Induction of pleckstrin by the Epstein-Barr virus nuclear antigen 3 family.

The Epstein-Barr virus (EBV) encoded nuclear antigens, EBNA-3, -4, and -6 (EBNA 3 family) are expressed in latently infected human B-cells and are involved in the transformation of lymphocytes by EBV. Human Burkitt's lymphoma (BL) dG75 cells which stably expressed either the complete EBNA 3 gene family or the vector alone were generated and changes in gene activity in these transfectants were assayed using the differential display of mRNA technique. For the first time, the human gene pleckstrin, which is thought to be involved in signalling and differentiation of hemopoietic cells, was found to be upregulated in the presence of the EBNA 3 protein family, but not in cells expressing the individual EBNA-3, -4, or -6 gene. Pleckstrin was increased up to sevenfold in different cell clones and the bulk culture of EBNA 3 gene family expressing cells as demonstrated by Northern blot. RT-PCR, and immunoblot in contrast to EBV-negative BL cells, pleckstrin RNA and protein were highly expressed in EBV growth transformed lymphoblastoid cell lines which are thought to play an important role in EBV persistence in vivo. These data suggest that induction of pleckstrin might be important for the EBV-controlled activation of cells and offers a unique biological system for analyzing pleckstrin function.

Base Sequence↗