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Biomedical subjects

N G Anderson

Publications and source records attributed to N G Anderson.

At least 55 records · Page 3Linked to original sources

Changes in the expression of guanine nucleotide-binding proteins during differentiation of 3T3-F442A cells in a hormonally defined medium.

Using specific antisera, the expression of the G protein alpha subunits, G8, G(i1), G(i2), G(i3) and G0, were determined in 3T3-F442A cells during their differentiation to adipocytes in a hormonally defined medium. Differentiation caused distinct increases in the expression of two Gs isoforms and decreases in the expression of both G(i2) and G(i3). Differentiation also resulted in a 2- to 4-fold increase in forskolin-stimulated adenylyl cyclase activity and a 15-fold increase in the response of cells to a beta-adrenergic agonist. The increase in Gs expression was also observed, to a lesser degree, in cells maintained at confluence under conditions where morphological conversion was negligible and the decreased expression of G(i2) and G(i3) and the increased beta-adrenergic responsiveness did not occur.

3T3 Cells↗

Simultaneous activation of p90rsk and p70s6k S6 kinases by growth hormone in 3T3-F442A preadipocytes.

Growth hormone promotes the differentiation of 3T3-F442A preadipocytes via unknown mechanisms. The ability of growth hormone to enhance the phosphorylation of ribosomal protein S6 through the activation of S6 kinases in this cell line was investigated. Growth hormone rapidly stimulated an S6 phosphotransferase activity measured in unpurified extracts. Using specific antisera, this activity was resolved into two components, comprising the p90rsk and p70s6k S6 kinases. Activation of these enzymes occurred simultaneously within minutes but proceeded with distinct time courses. p90rsk activation was transient, down-regulating within 60 min, whereas p70s6k activation was sustained beyond this time. The degree of activation of both S6 kinases by growth hormone closely paralleled their apparent phosphorylation status, with multi-site phosphorylation associated with full activation. Pretreatment of cells with a selective inhibitor of protein kinase C prevented activation of both S6 kinases by growth hormone but not by epidermal growth factor.

3T3 Cells↗

Prognostic significance of nonvisualization of the fetal stomach by sonography.

OBJECTIVE: To establish the prognostic significance of nonvisualization of the fetal stomach, we prospectively studied the course and outcome of 31 pregnancies in which a normal fluid-filled fetal stomach could not be seen during sonographic examination after 14 weeks' gestation. SUBJECTS AND METHODS: Between April 1989 and May 1991, 7200 sonographic examinations of fetuses after 14 weeks' gestation were done at our hospital. In 31 pregnancies (0.4% of all scans), a normal fluid-filled fetal stomach could not be seen on one or more sonograms after 14 weeks' gestation (range, 14-40 weeks; mean, 22 weeks). The following data were recorded for each examination: gestational age, visualization of the stomach, other fetal abnormalities, and volume of amniotic fluid. In each pregnancy, the average number of sonograms obtained was three (range, one-five). The fetal stomach was regarded as abnormal if the stomach bubble was absent or remained very small and unchanged for at least 45 min during sonography. RESULTS: The outcome was normal in 16 cases. The 15 abnormal outcomes included spontaneous fetal or neonatal death in five, pregnancy terminations in three, and persistent postnatal disability in seven. In 15 pregnancies (48%) lack of visualization of the fetal stomach was the only significant abnormal sonographic finding, but an abnormal outcome occurred in three. In 12 pregnancies, nonvisualization of the fetal stomach was a transient finding, yet three of those pregnancies resulted in persistent postnatal disability, and one was terminated because of severe maternal preeclampsia. A normal fluid-filled stomach was seen on the next sonogram in 15 cases, but five had an abnormal outcome. Only one of the four pregnancies in which a normal stomach was not seen on any subsequent sonogram had an abnormal outcome. Six of seven pregnancies with oligohydramnios had an abnormal outcome, and all three cases with polyhydramnios had an abnormal outcome. The prevalence of abnormal outcome was 88% when additional sonographic abnormalities were observed, but 20% when no other sonographic abnormality was seen. The overall prevalence of abnormal outcome when the fetal stomach was not visualized was 48%. CONCLUSIONS: Not all fetuses with a nonvisualized stomach after 19 weeks' gestation have a poor outcome. Not all fetuses with a transiently nonvisualized stomach have a normal outcome.

Female↗

Growth hormone activates mitogen-activated protein kinase and S6 kinase and promotes intracellular tyrosine phosphorylation in 3T3-F442A preadipocytes.

Physiological concentrations of growth hormone induced a rapid and transient activation of mitogen-activated protein kinase (MAP kinase) and S6 kinase in 3T3-F442A preadipocytes. These effects were abrogated by staurosporine and in cells chronically pretreated with phorbol esters, suggesting that protein kinase C is involved in the mechanism of activation. In addition, three cytosolic proteins exhibited a growth-hormone-dependent increase in tyrosine phosphorylation.

3T3 Cells↗

Placental compressibility: implications for indirect diagnosis of posterior placenta previa.

A number of problems beset the indirect diagnosis of posterior placenta previa using transabdominal ultrasound. We add a new potential complicating factor. In 128 pregnancies at or beyond 30 weeks' gestation, measurements were taken from the fetal skull to the maternal sacrum before and after compression. Up to 69% compressibility of the placenta was found in vivo and in vitro. Modified fetal skull to maternal sacrum measurement criteria were devised from the results. Placenta previa is highly unlikely if the measurement from the fetal skull to maternal sacrum is less than 10 mm before compression or less than 7 mm after compression. Placenta previa is probable if the measurement is greater than 20 mm before compression or greater than 15 mm after compression. In 40% of the cases, posterior placenta previa could not be excluded. We conclude that placental compressibility is an additional confounding problem for indirect ultrasound assessment of posterior placenta previa and that indirect assessment should be attempted only if maneuvers to image the lower uterine segment directly are unsuccessful.

Female↗

Efficacy of fetal part elevation to visualise internal cervical os.

The diagnosis or exclusion of placenta previa is best achieved by direct visualisation of the relationship of the lower edge of the placenta to the internal cervical os. In later pregnancy, the presenting fetal part frequently obscures this area. Elevation of the presenting part was attempted in 56 consecutive pregnancies of greater than 30 weeks gestation, with a success rate of 71%. This confirms that in a minority of pregnancies, other manoeuvres or ultrasound techniques are necessary to visualise the lower placental margin directly.

Female↗

Prognosis in fetal cystic hygroma.

Axillary and lateral cervical fetal cystic hygromas in a fetus with normal karyotype are described. Fetal death at 25 weeks' gestation occurred. A literature review revealed that for cystic hygroma 42% of infants are 45XO, 38% have a normal karyotype, and 18% have trisomies. Prognosis is grim if the karyotype is abnormal or if hydrops or bilateral pleural effusions are present. Survival rate progressively improves with normal karyotype (27%), unilateral pleural effusion (40%), atypical location (56%), and resolution of cystic hygroma (71%). No single feature signifies 100% survival. The overall survival rate for fetal cystic hygroma is 10%. Prognosis remains guarded regardless of all other factors until the fetus reaches 26 weeks' gestation, after which time a 67% chance of ultimate survival can be expected. Only 42% of documented survivors were completely normal at follow-up.

Axilla↗

Raf-1 is a potential substrate for mitogen-activated protein kinase in vivo.

MAP (mitogen-activated protein) kinase is shown to phosphorylate baculovirally expressed Raf-1 in vitro, generating one major tryptic phosphopeptide which co-migrated with a peptide from Raf-1 32P-labelled in situ. This peptide also undergoes an insulin-dependent increase in labelling. Thus the serine/threonine kinase Raf-1 may be a substrate for MAP kinase in vivo.

Animals↗

Activation of mitogen-activated protein kinase in BC3H1 myocytes by fluoroaluminate.

Treatment of BC3H1 myocytes or 3T3-L1 fibroblasts with fluoroaluminate (AlF4-), a direct activator of G proteins, increased the tyrosine phosphorylation of a 42-kDa cytosolic protein. AlF4- induced a parallel increase in protein kinase activity toward myelin basic protein (MBP) in partially purified cell extracts. To test whether AlF4- was activating the 42-kDa MAP (mitogen-activated protein) kinase, extracts from AlF4--treated cells were taken through the chromatographic steps routinely used to purify MAP kinase from growth factor-stimulated cells. Following phenyl-Superose chromatography, a peak of MBP kinase activity eluted at a position characteristic of MAP kinase. Immunoblotting of the active fractions with anti-phosphotyrosine antibodies revealed a single reactive protein band of Mr 42,000. Stimulation of MAP kinase by AlF4- was rapid, peaking within 15 min and persisting for at least 1 h. In contrast, the activation of MAP kinase by insulin was transient, characteristic of its activation by growth factors in other cell types. Although concentrations of sodium fluoride greater than 1 mM also activated MAP kinase, this effect was shown to be dependent upon the simultaneous presence of aluminum ions in the medium. Activation of MAP kinase by AlF4- was not affected by either cellular depletion of protein kinase C or pretreatment of cells with pertussis toxin. Potential sites of action of AlF4- are discussed. These findings suggest that activation of a G protein(s) in intact cells can initiate events that result in tyrosine phosphorylation and activation of MAP kinase.

Aluminum↗

A two-dimensional gel database of human plasma proteins.

An updated two-dimensional electrophoretic map of human plasma proteins is presented, together with a complete listing of the individual protein spots, their locations, size and isoelectric points relative to internal charge standards. Forty-nine polypeptide species are identified, many consisting of multiple spots differing in glycosylation or sequence (e.g., immunoglobulins). A further series of 35 as yet uncharacterized proteins is indicated.

Blood Proteins↗

A two-dimensional gel database of rat liver proteins useful in gene regulation and drug effects studies.

A standard two-dimensional (2-D) protein map of Fischer 344 rat liver (F344MST3) is presented, with a tabular listing of more than 1200 protein species. Sodium dodecyl sulfate (SDS) molecular mass and isoelectric point have been established, based on positions of numerous internal standards. This map has been used to connect and compare hundreds of 2-D gels of rat liver samples from a variety of studies, and forms the nucleus of an expanding database describing rat liver proteins and their regulation by various drugs and toxic agents. An example of such a study, involving regulation of cholesterol synthesis by cholesterol-lowering drugs and a high-cholesterol diet, is presented. Since the map has been obtained with a widely used and highly reproducible 2-D gel system (the Iso-Dalt system), it can be directly related to an expanding body of work in other laboratories.

Animals↗

Normal size left ventricle on antenatal scan in lethal hypoplastic left heart syndrome.

We present a case of lethal hypoplastic left heart syndrome missed at routine 20-week antenatal ultrasound examination because the left ventricle was of normal size on the standard four-chamber cardiac view. Hypoplastic left heart syndrome includes a spectrum of cardiac malformations. This case illustrates the difficulty in excluding the diagnosis of hypoplastic left heart syndrome on a single view from one antenatal second-trimester ultrasound examination.

Diagnostic Errors↗