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Biomedical subjects

G Wright

Publications and source records attributed to G Wright.

At least 127 records · Page 7Linked to original sources
PubMed1993

Repeated sperm injection under the zona following initial fertilization failure.

When fertilization fails following micromanipulative under-zona insemination, it is possible to repeat the procedure adding more spermatozoa to achieve fertilization, embryonic development and pregnancy. We report on 18 human in-vitro fertilization cycles where this approach was used. In nine cycles only late-fertilized embryos were available for transfer, and these gave rise to two viable pregnancies (22.2% per transfer). In six cycles, where a mixture of late- and timely fertilized embryos were available for transfer, two viable pregnancies arose (33.3% per transfer). In three cycles no fertilization was achieved even after reinsemination by repeated under-zona insemination.

Embryo Transfer↗
PubMed1993

A comparison of two systems for assessing cerebral venous oxyhaemoglobin saturation during cardiopulmonary bypass in humans.

The Somanetics Invos 3,100 cerebral oximeter is a new noninvasive device which measures the regional oxygen saturation of haemoglobin within the cerebral microvasculature by infrared spectroscopy. It was used in nine patients undergoing elective cardiac surgery and its results were compared with measurements of jugular venous bulb saturations obtained by the Oximetrix Opticath oximetry system. The index value of jugular venous bulb saturation was obtained by analysis of jugular bulb blood in an Il282 cooximeter. The cerebral oximeter was less accurate and precise (standard deviation of difference 14.1%) than the Oximetrix system (standard deviation of the difference 2.65%) and also demonstrated a systematic error in bias unrelated to cerebral perfusion pressure. The cerebral oximeter may therefore be less useful than jugular venous bulb saturation in the clinical management of patients undergoing cardiopulmonary bypass.

Adult↗
PubMed1993

Human IGFBP-1 is phosphorylated on 3 serine residues: effects of site-directed mutagenesis of the major phosphoserine.

Human IGFBP-1 is phosphorylated by cells in culture and is present in both phosphorylated and nonphosphorylated forms in human fetal serum and amniotic fluid. We have found immunoprecipitable [32P]IGFBP-1 in the conditioned media of both Chinese hamster ovary (CHO) cells (stabley transfected and secreting human IGFBP-1) and human hepatoma (HepG2) cells metabolically labelled with [32P]orthophosphate. Phosphoamino acid analysis of this [32P]IGFBP-1 demonstrates that only serine residues are phosphorylated. Four phosphorylated isoforms of IGFBP-1 can be separated from one nonphosphorylated form by nondenaturing gel electrophoresis. Since we have shown that the nonphosphorylated form of IGFBP-1 has a lower affinity for IGF-I compared to phosphorylated forms and a greater potentiating effect of IGF-I actions, we determined which serine residues in human IGFBP-1 are phosphorylated. After metabolically labelling IGFBP-1 with 32P, the purified phosphoprotein was digested first with trypsin and then with endoproteinase Glu-C. By radiosequencing the resulting 32P-labelled phosphopeptides, we found 3 serine residues to be phosphorylated. Approximately 70% of incorporated 32P was attributed to Ser101, while Ser169 accounted for approximately 25% and Ser119 for 5%. To investigate the physiologic importance of Ser101, this residue (and the nonphosphorylated Ser98) were changed to alanine by site directed mutagenesis of a human IGFBP-1 expression vector, followed by transfection into CHO cells. The [Ala98,101]IGFBP-1 purified from the conditioned media of these cells had the following characteristics: 1) when labelled with [32P]orthophosphate, it contained 63% less radioactivity than wild type IGFBP-1; 2) when analyzed by nondenaturing gel electrophoresis, it contained none of the most rapidly migrating and most rapidly migrating and most highly phosphorylated isoform, more of the nonphosphorylated isoform, and more of the most slowly migrating phosphorylated isoform; and 3) its affinity for IGF-I was reduced 2.5-fold and was midway between wild type IGFBP-1 from transfected CHO cells and dephosphorylated IGFBP-1. We conclude that Ser101 represents the major site of phosphorylation of IGFBP-1 and that while phosphorylation of Ser101 increases affinity of IGFBP-1 for IGF-I, phosphorylation of Ser169 and/or Ser119 also contributes to the high affinity of fully phosphorylated IGFBP-1.

Alanine↗
PubMed1993

Creation of state-level Medicare database for healthcare evaluation applications.

The Health Care Quality Improvement Initiative (HCQII) of the Health Care Financing Administration (HCFA) calls for Professional Review Organizations (PROs) to undertake pattern analysis of large administrative datasets for the purposes of quality of care assessment. The limitations of such administrative databases (primarily the MEDPAR file and derivatives thereof) include impoverished information regarding clinical attributes of Medicare enrollees and the process and outcome of their healthcare. This paper describes preliminary efforts to address this problem by the creation of a database, the PRO Concatenated Database (PCD), from the pooled implicit judgment review data of four Peer Review Organizations (PROs). The data elements comprising the PCD were carefully selected to provide important information regarding quality and appropriateness of care. Preliminary inter-state comparative studies employing the PCD are discussed. A method is also described by which the analytical power of state-level databases may be enhanced by linkage to state-level Modeled MEDPAR data which are issued by HCFA and contain patient-level risk-adjusted mortality data. This approach to the acquisition of data whose clinical content is enriched may prove to be particularly useful to the PRO community during the pattern analysis phase of the HCQII. Such analyses will evolve into more detailed studies involving primary data collection followed by dissemination of the results to local healthcare providers. In this manner, the PCD may facilitate rapid feedback regarding the effectiveness of healthcare delivery to the local community.

Aged↗
PubMed1992

Inhibition of binding of bacteria to amniochorionic membranes by amniotic fluid.

The immunological composition of amniotic fluids is shown to be of such a lower order of activity that its role in fetal protection may be limited. Also, amniotic fluids were found not to have classical antibiotic activity. Amniotic fluids (25/31), however, were found to inhibit, by 27.5% to 88.2%, three target bacteria from binding to discs of amniochorionic membranes. This inhibition is also demonstrable with the monosaccharides alpha-D(+)-fucose, D(+)-galactose, alpha-D-glucose, alpha-D-lactose and bovine serum albumin-lactose conjugate, whereas other glycoconjugates enhanced bacterial binding. This demonstrates that the test bacteria bind to the amniochorionic membranes using bacterial lectins. In intraamniotic infection bacterial lectins may be complexed by amniotic fluid glycoconjugates which prevent the bacteria from binding to the amniochorionic membranes. This would explain asymptomatic infection and in the absence or reduced levels of the glycoconjugates the bacteria would bind to the amniochorionic membranes giving rise to symptomatic infection.

Amnion↗
PubMed1992

Quantitative structure-activity relationships of N2-phenylguanines as inhibitors of herpes simplex virus thymidine kinases.

Quantitative structure-activity relationships of the Hansch-type were developed to account for inhibition of thymidine kinases from Herpes simplex viruses types 1 and 2 (HSV1,2) by N2-phenylguanines. Derivatives with meta and/or para substituents on the phenyl ring display a wide range of overlapping, but not identical, potencies as inhibitors of the enzymes. IC50 values for 36 (HSV1) and 35 inhibitors (HSV2) were used to develop equations using hydrophobic (pi), electronic (sigma, R), and group size (MR) parameters. Equations 1 and 2 with correlation coefficients of 0.797 and 0.805, respectively, were obtained for inhibitors of the types 1 and 2 enzymes. Potencies were correlated positively with pi values of meta substituents but negatively with pi values of para substituents in the phenyl ring. Positive correlations were also obtained with the resonance parameter R of para substituents and with sigma constants of meta substituents. The most potent inhibitor of both enzymes was N2-[m-(trifluoromethyl)phenyl]guanine, although HSV2 thymidine kinase was more sensitive to certain compounds than the HSV1 enzyme.

Antiviral Agents↗
PubMed1992

Identification of the forms of insulin-like growth factor-binding proteins produced by human fibroblasts and the mechanisms that regulate their secretion.

Human fibroblasts secrete insulin-like growth factor-binding proteins (IGFBPs) that can modify insulin-like growth factor (IGF) I action. We have determined the molecular identities of three forms of IGFBPs that are secreted by human fibroblasts in vitro. Ligand blot analysis of fibroblast conditioned media revealed that the M(r) 43,000 and 39,000 forms were the most abundant, but that M(r) 31,000 and 24,000 forms were also present. An antiserum that was specific for IGFBP-5 reacted with the M(r) 31,000 form, and an IGFBP-4-specific antiserum recognized only the M(r) 24,000 form. The M(r) 39,000 and 43,000 forms were detected by IGFBP-3 antiserum. Further proof that fibroblasts synthesized these forms of IGFBPs was obtained by Northern blotting. A cDNA probe for IGFBP-3 hybridized with a 2.4-kilobase (kb) transcript, whereas a cDNA probe for IGFBP-5 recognized a single 6.0-kb transcript, and an IGFBP-4 cDNA probe recognized 2.2- and 2.0-kb transcripts. IGF-I and -II caused a minimal (less than 43%) increase in IGFBP-5 mRNA abundance and had no effect on IGFBP-4 mRNA abundance. IGF-I and -II (100 ng/ml) stimulated 6-8-fold increases in IGFBP-5 levels, whereas IGFBP-4 was inhibited. Insulin failed to elicit any change in IGFBP-5, suggesting that binding of the IGFs to IGFBPs was required to detect the increase. Immunoblotting for IGFBP-5 revealed an M(r) 23,000 (non-IGF-I-binding) fragment. To determine if the IGFs were influencing proteolytic degradation of IGFBP-5, pure IGFBP-5 was added to fibroblast cultures and incubated for 4 h at 37 degrees C. The amount of fragment formation was attenuated by the presence of IGF-I and -II, but not insulin, suggesting that this is a mechanism by which the IGFs act to modulate IGFBP-5 concentration. In contrast to the IGFs, forskolin, which increased IGFBP-4 and -5 mRNA abundance and secretion, had no effect on fragment formation. The results show that human fibroblasts synthesize and secrete IGFBP-3, -4, and -5 and that changes in intracellular cAMP regulate synthesis, whereas the IGFs regulate IGFBP-4 and -5 levels by post-transcriptional mechanisms.

Amino Acid Sequence↗
PubMed1992

Massive epistaxis due to pseudoaneurysm. Treated with detachable balloons.

A case of massive epistaxis refractory to nasal packing and bilateral surgical ligation of the internal maxillary and ethmoidal arteries is presented. Angiography revealed a pseudoaneurysm of the cervical portion of the internal carotid artery, and intravascular detachable balloons were used for epistaxis control. The appropriate use of intravascular diagnostic and therapeutic techniques is described.

Adult↗
PubMed1992

Molecular analysis of human chromosome 16 cosmid clones containing NotI sites.

To test the feasibility of using cloned NotI sites as markers for physical mapping, we have screened for cosmid clones spanning the NotI sites on human Chromosome (Chr) 16. Fluorescence in situ hybridization analysis of these clones confirms the previously reported cluster of NotI sites on 16p13.3. Methylation status of the cloned NotI sites on genomic DNA was established by hybridization of the cosmids to Southern blots containing EcoRI and EcoRI/NotI digest of genomic DNA. These results indicated that four of six clones included in our study can be used as linking clones for physical mapping. Two clones have NotI sites which are not cleavable in the cell lines tested. In one clone, the NotI site exists as an isolated rare-cutting restriction enzyme site, whereas in the other clone the NotI site appears to be island-related.

Blotting, Southern↗
PubMed1992

Epidemiology by computer.

Collecting epidemiological data from a large community sample has, in the past, been a costly and time-consuming exercise. This paper outlines a methodology for undertaking such research by using a set of standard psychiatric questionnaires, including a computerised version of the Diagnostic Interview Schedule Screening Interview on a portable laptop computer. The study of 1009 country South Australian subjects found that this technique provided prevalence estimates similar to those obtained from the more established Diagnostic Interview Schedule, with the added benefit that all interviews were successfully carried out by lay interviewers under minimal supervision, in the subject's home.

Computers↗
PubMed1992

Expression of human alpha 1 antitrypsin in transgenic sheep.

We have recently described the production of large amounts (< or = 65 grams per litre) of enzymatically active human alpha 1 antitrypsin in the milk of transgenic sheep (Wright et al., 1991). Here, we describe in more detail the expression of the human protein in the milk of these animals throughout the lactation period. Human alpha 1 antitrypsin is also found at much lower levels in the plasma of transgenic ewes before, during and after lactation. It is also detected in male plasma at very low levels. We have previously shown human alpha 1 antitrypsin purified from transgenic sheep milk to be indistinguishable from commercially available human plasma derived alpha 1 antitrypsin in terms of gross sugar content and in vitro activity. Here we extend this comparison to more detailed analyses of glycosylation state, amino-terminal sequence, pI value, and molecular weight determination by mass spectrometry.

Amino Acid Sequence↗
PubMed1992

The effects of aspartate and 2-oxoglutarate upon glycolytic energy metabolites and mechanical recovery following global ischaemia in isolated rat hearts.

The hypothesis that aspartate and 2-oxoglutarate might help to relieve the inhibition of glycolysis during global myocardial ischaemia and improve post-ischaemic mechanical recovery was tested in isolated rat hearts. The hearts were attached to a lumped parameter model of the rat vascular impedance and initially perfused in the working mode with buffered Krebs-Henseleit solution containing 10.1 mmol/l glucose, with or without 3.3 mmol/l of aspartate and 3.3 mmol/l of 2-oxoglutarate, prior to imposing global ischaemia for 5, 10 or 15 mins. The addition of aspartate and 2-oxoglutarate improved the preservation of tissue CP after 5 mins of ischaemia and of ATP after 10 mins of ischaemia. The total adenine nucleotide pool was higher in the supplemented hearts after all three periods of ischaemia. Dihydroxyacetone phosphate, alanine, succinate and lactate accumulated during ischaemia, but the dihydroxyacetone phosphate accumulation was reduced while the alanine and succinate concentrations were increased by the addition of aspartate and 2-oxoglutarate to the perfusate. These observations lend support to the hypothesis that ischaemia arrests glycolysis at the glyceraldehyde phosphate dehydrogenase step due to a lack of oxidised nicotinamide adenine dinucleotide. Increasing the substrate concentrations of aspartate and 2-oxoglutarate may permit glycolysis to proceed for longer into the period of ischaemia by stimulating an additional pathway for nicotinamide adenine dinucleotide reoxidation. Small improvements in mechanical recovery were associated with the metabolic changes.

Adenine Nucleotides↗
PubMed1992

Electroejaculation in combination with in vitro fertilization and gamete micromanipulation for treatment of anejaculatory male infertility.

OBJECTIVE: Failure to ejaculate may be overcome by use of electroejaculation. However, such semen samples are often unsuitable for therapies like intrauterine insemination. The combination of electroejaculation with in vitro fertilization, including gamete micromanipulation, should improve chances of fertilization and pregnancy in such cases. STUDY DESIGN: Within a private infertility clinic electroejaculation in combination with intrauterine insemination was carried out in 18 cycles (10 couples). Four couples went on to receive therapy by electroejaculation plus in vitro fertilization, along with six other couples (15 cycles total) with semen too poor for intrauterine insemination. RESULTS: One term pregnancy arose in the electroejaculation-intrauterine insemination group, and one term pregnancy plus one continuing pregnancy arose from two couples (three cycles) who underwent in vitro fertilization with conventional insemination after electroejaculation. Six couples (nine cycles) had embryos arising only from gamete micromanipulation transferred, and this yielded two term pregnancies, one spontaneous abortion, and a biochemical pregnancy. Two couples (three cycles) failed to achieve fertilization even with micromanipulation; however, donor-inseminated eggs gave rise to two term pregnancies and one continuing pregnancy in these patients. CONCLUSIONS: This report confirms the feasibility of in vitro fertilization in conjunction with electroejaculation and extends the therapy to incorporate gamete micromanipulation.

Adult↗
PubMed1992

Rescuing transgene expression by co-integration.

To test whether foreign gene expression can be improved in transgenic mice by manipulating the site of integration, we co-integrated the efficiently expressed sheep beta-lactoglobulin gene with two poorly expressed beta-lactoglobulin-derived hybrid genes encoding human proteins. In each case, we observed a significant improvement in the frequency and level of expression of the hybrid gene. "Rescuing" transgene expression by co-integration may provide a general solution for improving the efficiency of heterologous gene expression in transgenic animals.

Animals↗
PubMed1992

Value of fine needle aspiration biopsy cytology in the diagnosis of discrete hepatic lesions suspicious for malignancy.

Ninety-five sequential computerized tomography (CT) guided fine needle aspirates (FNA) of the liver, taken between January 1986 and December 1989 were reviewed to assess the accuracy of this method in diagnosing discrete hepatic lesions suspicious for malignancy. Clinical follow-up information, or a tissue diagnosis or both were available in 71 of these cases. False-negative results were found in four of the cases. Forty-six cases in the group gave a positive result with FNA and confirmatory tissue diagnosis was made in 25 of these cases. Detailed clinical follow-up produced additional support for the diagnosis in 20 other cases. Twenty-four cases were negative but clinical follow-up indicated that there were four false-negative diagnoses. The one false-positive case in this series was diagnosed as a hepatocellular carcinoma in a patient with haemochromatosis. Overall, the results gave a sensitivity of 90% and a specificity of 87%.

Adult↗