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Biomedical subjects

L Philipson

Publications and source records attributed to L Philipson.

At least 19 recordsLinked to original sources
PubMed1992

The growth arrest-specific gene, gas1, is involved in growth suppression.

This report describes the structure of the mRNA, the protein product, and the growth-regulating activity of one of the growth arrest-specific genes, gas1. From the predicted amino acid sequence, in vitro translation of gas1 mRNA, and immunofluorescence of cells in culture, it appears that the gas1 protein is an integral plasma membrane protein whose expression is linked to growth arrest. When gas1 is overexpressed from a constitutive promoter in quiescent cells, the serum-induced transition from the G0 to the S phase of the cell cycle is inhibited without affecting the normal early serum response. Ectopic expression of the gas1 gene by microinjection in normal and transformed NIH 3T3 cell lines with the notable exception of SV40-transformed 3T3 cells leads to inhibition of DNA synthesis. Thus, gas1 appears to be one component of a negative circuit that governs growth suppression. Its effect is, however, abolished in SV40-transformed cells.

3T3 Cells↗
PubMed1992

Consistent policy?

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Base Sequence↗
PubMed1992

Regulation and expression of a growth arrest-specific gene (gas5) during growth, differentiation, and development.

The growth arrest-specific gas5 gene was isolated from mouse genomic DNA and structurally characterized. The transcriptional unit is divided into 12 exons that span around 7 kb. An alternative splicing mechanism gives rise to two mature mRNAs which contain either 11 or 12 exons, and both are found in the cytoplasm of growth-arrested cells. In vivo, the gas5 gene is ubiquitously expressed in mouse tissues during development and adult life. In Friend leukemia and NIH 3T3 cells, the levels of gas5 gene mRNA were high in saturation density-arrested cells and almost undetectable in actively growing cells. Run-on experiments indicated that the gas5 gene is transcribed at the same level in both growing and arrested cells. On the other hand, in dimethyl sulfoxide-induced differentiating cells a sharp decrease in the rate of transcription was observed shortly before the cells reached the postmitotic stage. These results indicate that in density-arrested cells accumulation of gas5 mRNA is controlled at the posttranscriptional level while in differentiating cells expression is regulated transcriptionally.

3T3 Cells↗
PubMed1991

From growth arrest to growth suppression.

Since the introduction of the cell cycle concept two approaches to study growth regulation of cells have been proposed. One claims that cells are naturally quiescent, requiring a stimulatory encouter with growth factors for induction of cell division. The other considers cellular multiplication as the natural steady-state; cessation of multiplication is thus a restriction imposed on the system. In the latter case emphasis is mainly on the signals involved in arrest of multiplication. This Prospect focuses on specific events occurring in mammalian cells at growth arrest, senescence, and terminal differentiation, specifically emphasizing the growth inhibitory factors, tumor suppressor genes, and other signals for growth suppression.

Animals↗
PubMed1991

Behavioral medicine treatment in chronic constipation with paradoxical anal sphincter contraction.

Nine women and five children with severe chronic constipation received behavioral medicine therapy. Before treatment, all patients had a paradoxical contraction of the external anal sphincter at defecation attempts as demonstrated with electromyography and/or anorectal manometry. An electromyographic biofeedback device connected to an anal probe was used for the training that was performed on a regular toilet seat during five 1-hour sessions. Thirteen of the patients improved considerably and could learn to defecate spontaneously, and the use of laxatives ceased or diminished. Simultaneously with improvement, the paradoxical anal contraction disappeared. The results remained after 6 months, although two of the patients had received booster sessions of biofeedback training during follow-up.

Adolescent↗
PubMed1991

Cloning of a growth arrest-specific and transforming growth factor beta-regulated gene, TI 1, from an epithelial cell line.

By cDNA cloning and differential screening, five genes that are regulated by transforming growth factor beta (TGF beta) in mink lung epithelial cells were identified. A novel membrane protein gene, TI 1, was identified which was downregulated by TGF beta and serum in quiescent cells. In actively growing cells, the TI 1 gene is rapidly and transiently induced by TGF beta, and it is overexpressed in the presence of protein synthesis inhibitors. It appears to be related to a family of transmembrane glycoproteins that are expressed on lymphocytes and tumor cells. The four other genes were all induced by TGF beta and correspond to the genes of collagen alpha type I, fibronectin, plasminogen activator inhibitor 1, and the monocyte chemotactic cell-activating factor (JE gene) previously shown to be TGF beta regulated.

Amino Acid Sequence↗
PubMed1991

Epidural anesthesia with 0.5% bupivacaine: influence of age on sensory and motor blockade.

To determine the influence of age on epidural blockade, 10 elderly male patients (mean age, 73 yr) and 11 young male volunteers (mean age, 25 yr) received epidural anesthesia with 20 mL of 0.5% bupivacaine with epinephrine at the L2-3 interspace. Median cephalad analgesia level (pinprick) was T-4 in the elderly and T-10 in the young subjects (P less than 0.01). The duration of analgesia at the L-1 to S-3 segments was about 60 min shorter in the older patients than in the young volunteers (P less than 0.05). Motor blockade was evaluated quantitatively by isometric muscle force measurements in the lower extremities and by electromyographic recordings from the abdominal and quadriceps muscles. Motor blockade in the lower extremities was also assessed qualitatively by the Bromage scale. The intensity of motor blockade was not influenced by age. The mean duration of maximal motor blockade of the lower abdominal muscles was 69 min in elderly patients and 140 min in young subjects (P less than 0.05). The corresponding mean duration in the lower extremities was approximately 1.5 h in the older patients and 3 h in the young subjects (P less than 0.01). The elderly patients could be mobilized 2 h earlier than the young volunteers. Duration of Bromage grade 1 was about 1.5 h shorter in the elderly than in the young subjects (P less than 0.01). Not until 1.5-2 h after attainment of Bromage grade 0 was the muscle force in the lower extremities restored to 90% of baseline value. The authors conclude that cephalad spread was more extensive and duration of epidural blockade was shorter in elderly patients versus younger volunteers.

Adult↗
PubMed1991

Single cell assay with an automated capillary microinjection system.

An automated capillary microinjection system with computer controlled positioning of the cells and of the capillary, and its applications and advantages are described. About 1500 injections are possible in one hour, with high reproducibility. In cytoplasmic and nuclear injections more than 90% and 85% of the cells are successfully injected. Using FITC-Dextran at a concentration of 0.5% as a fluorescently labelled coinjection marker, 99% of the cells can be retrieved in culture medium even 48 hours after injection. The coordinates of the cells are stored in the computer and accuracy in statistical evaluation of experiments is improved in comparison to the manual techniques. Methods for preparation and handling of glass capillaries were developed resulting in reproducible form and significantly reduced clogging rate. The improved characteristics offered by this system are demonstrated in studies leading to the confirmation of existence of mRNA(s) inhibiting cell proliferation. Functional screening by cell injections of cDNA libraries and of size fractionated mRNA molecules can be performed efficiently with the automated microinjection system.

Animals↗
PubMed1990

Cell proliferation inhibited by MyoD1 independently of myogenic differentiation.

Cell growth and differentiation are usually mutually exclusive. Transformation of myoblasts by retroviruses containing the myc oncogene inhibits differentiation, preventing cells from withdrawing from the cell cycle. If cell-cycle withdrawal is a prerequisite for myoblast differentiation, it is probably an early event in terminal cell differentiation, but this has not yet been established. MyoD1 regulates myogenesis. It is expressed only in skeletal muscle, but can convert other cells to muscle cells. The MyoD1 protein, a nuclear phosphoprotein in part similar to the myc family of proteins, is a DNA-binding protein binding to the enhancer sequences of the muscle-specific creatine phosphokinase gene. Thus, introduction of MyoD1 into cells provides a simple approach to study the effect of induction of differentiation on cell growth. In cultured NIH 3T3 cells, inhibition of cell proliferation occurs within 18 hours, and expression of myosin starts after 72 hours. Furthermore, injection of MyoD1 into quiescent NIH 3T3 cells inhibit cell proliferation independently of induction of differentiation. Deletion of the myc-like domain in the MyoD1 gene eliminates the inhibition of DNA synthesis, but substitution of the basic domain with the analogous domain from the E12 transcription factor inhibits growth yet fails to induce differentiation. Inhibition of DNA synthesis, therefore, seems to be controlled separately from myogenic differentiation.

Animals↗
PubMed1990

Influence of intravenous local anaesthetics upon quadriceps muscle function.

This study was undertaken to assess the effects of intravenous administration of mepivacaine and etidocaine on muscle function. Seven male volunteers were given mepivacaine (5 mg/kg) and etidocaine (50 mg) intravenously, on separate occasions. A reference group of 11 male volunteers received 0.9% saline solution intravenously. Muscle function was tested by measurements of isometric muscle force of knee extension and by quantitative electromyographic (EMG) recordings from the quadriceps muscle during knee extension at different degrees of isometric muscle force. At the end of the mepivacaine and etidocaine infusions, the mean venous plasma concentrations of the two anaesthetic agents were 2.9 and 1.2 micrograms/ml, respectively. The muscle strength remained unchanged during infusion of the two local anaesthetics. Mepivacaine had a minor effect on the mean rectified EMG amplitudes at the end of the infusion at maximal voluntary muscle contraction, but no such effect was observed at submaximal knee extension force. However, at the plasma concentrations mentioned above, the clinical influence of intravenous infusion of the local anaesthetics on muscle function was negligible.

Adult↗
PubMed1990

Regulation of expression of growth arrest-specific genes in mouse fibroblasts.

The suppression of growth arrest-specific (gas) gene expression by serum appeared to be independent of protein synthesis, but expression in resting cells was sensitive to 2-aminopurine, an inhibitor of intracellular protein kinases. Although accumulation of gas gene mRNA was reduced by serum, nuclear transcription of the gas-2, -3, and -5 genes was observed in serum-stimulated cells, indicating that posttranscriptional events may regulate mRNA levels. Growth induction by serum, on the other hand, led to suppression of transcription of the gas-1 gene. Cell cycle regulation and the serum response of gas-1 were lost in ras-transformed cells.

Animals↗
PubMed1990

A growth arrest-specific (gas) gene codes for a membrane protein.

A set of growth arrest-specific (gas) genes whose expression is negatively regulated by serum has recently been identified. We report on the detailed analysis of one of these genes (gas3). The kinetics of regulation by the presence and absence of serum were investigated, and it was found that this gene is regulated at the post-transcriptional level. The encoded protein deduced from the nucleotide sequence showed some similarity to a mitochondrial oxyreductase, and in vitro translation established that the protein product is a transmembrane glycoprotein.

Amino Acid Sequence↗