Biomedical subjects

L Stevenson

Publications and source records attributed to L Stevenson.

12 recordsLinked to original sources

PubMed1995

A novel regulatory region is required for trophoblast-specific transcription in transgenic mice.

The trophectoderm epithelium of the blastocyst is the first tissue to differentiate in the mammalian embryo and gives rise to all cells of the trophoblast lineage. These cells form the majority of the fetal component of the placenta, which is critical for intrauterine development. Our interest in the molecular determinants of trophoblast lineage development has led us to undertake an analysis of the regulatory region of a trophoblast-specific gene termed 4311. The transcription start site was mapped by both primer extension and RNase protection analyses. We show that cloned 4311 upstream sequences are able to confer the correct temporal and spatial expression pattern of 4311 on a reporter gene in transgenic mice. In addition, we have characterized a 340-bp region, 3.7 kb upstream of the transcription start, that is sufficient for the specific expression of lacZ in cells of the developing spongiotrophoblast in transgenic mice. Delineation of a diploid trophoblast-specific regulatory region will facilitate the identification of factors that may regulate the development of this lineage.

Animals↗

PubMed1994

Expression of the non-structural protein NS1 of bluetongue virus in bacteria and yeast: identification of two antigenic sites at the amino terminus.

cDNA transcribed from bluetongue virus serotype 1 (Australia) dsRNA 5 coding for non-structural protein NS1 was amplified in a polymerase chain reaction and ligated downstream of the T7 RNA polymerase promoter in the bacterial expression plasmid pET-5b, as a fusion protein with glutathione S-transferase using the pGEX bacterial expression system or the metallothionein promoter in the yeast expression plasmid pYELC5. The linear epitopes bound by six monoclonal antibodies to NS1 were localised to two antigenic regions at the amino terminus by Western blots using a series of carboxy-terminal truncations of the NS1 protein overexpressed in Escherichia coli. Expression of truncated NS1 genes using the pGEX expression system in E. coli enabled a more detailed map of the two epitopes to be constructed. The first epitope is thought to lie between amino acid residues 40-59, while the second is defined by the peptide sequences flanking amino acid 96.

Base Sequence↗

PubMed1992

Low-dose recombinant interleukin-2 and low-dose cyclophosphamide in metastatic breast cancer.

We undertook a preliminary study to examine the response rate of recombinant interleukin-2 (rIL-2) in patients with advanced measurable breast cancer, in a phase II clinical trial. The regimen we utilized was designed to allow outpatient administration. A treatment cycle consisted of low-dose cyclophosphamide (350 mg/m2) given on day -3 followed by the bolus administration of rIL-2 (3.6 x 10(6) Cetus units/m2) on days 1-5, and 8-12. Toxicity was significant but acceptable. One partial remission was seen in 13 evaluable patients. In 2 additional patients clear evidence of an antitumor response was observed. The study was terminated prematurely owing to a shortage of rIL-2. Additional evaluation of rIL-2 in breast cancer appears warranted.

Adult↗

PubMed1991

Gastrointestinal complications after cardiac transplantation: a spectrum of diseases.

Cardiac transplantation has become an accepted treatment modality for end-stage cardiac failure. The gastrointestinal (GI) tract represents a potential source of posttransplant morbidity and mortality. To define the scope of this problem, records of all patients undergoing cardiac transplantation at UCLA between January 1984 and July 1989 were reviewed. In all, there were 120 patients (90 males and 30 females) with a mean age of 45.4 yr. Among them, there were 61 patients (51%) who developed a total of 112 posttransplant GI complications. Of the entire 120 patients, 41 (34%) developed minor complications and 20 (17%) sustained major GI morbidity. Eighteen patients (15%) underwent either endoscopy or surgical intervention. These data suggest that most cardiac transplant recipients will experience some form of GI complication, although most are minor and can be managed conservatively. However, when major, life-threatening complications occur, evaluation and intervention should proceed expeditiously. The gastroenterologist and GI surgeon should play complimentary roles in the care of these complicated patients.

Adolescent↗

PubMed1990

Endothelial renin-angiotensin pathway. Adrenergic regulation of angiotensin secretion.

Cultured bovine aortic endothelial cells (BAECs) express the complete renin-angiotensin system and secrete angiotensins. In this study, we examined the adrenergic influence on the secretion of angiotensins from BAECs. Angiotensins were determined by high-performance liquid chromatography and radioimmunoassay. At basal state, BAECs contain angiotensin I, angiotensin II, and angiotensin III at concentrations of 2.5 +/- 1.3, 4.8 +/- 2.3, and 3.4 +/- 1.5 pg/10(6) cells, respectively. Angiotensin I, angiotensin II, and angiotensin III concentrations in the culture medium were 8.3 +/- 4.4, 9.4 +/- 3.5, and 9.9 +/- 3.3 pg/10(6) cells, respectively. Isoproterenol (0.1-10 microM) increases secretion of angiotensins I, II, and III in a dose-dependent manner. Increase in angiotensin secretion induced by isoproterenol (10 microM) can be inhibited by beta 2-adrenoceptor antagonist ICI 118,551 (1 microM), but not by beta 1-adrenoceptor antagonist atenolol (1 microM). Forskolin (1-1,000 microM) mimics the isoproterenol-induced response. In contrast, alpha-adrenergic agonist phenylephrine (1-100 microM) inhibits the secretion. Pretreatment of BAECs with captopril (1 microM) inhibits the accumulation of angiotensin II and angiotensin III in the culture medium, but not angiotensin I. These findings suggest that BAEC production and/or secretion of angiotensins is regulated by adrenergic mechanisms.

Angiotensin I↗

PubMed1990

Active-specific immunotherapy for melanoma.

Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.

Adjuvants, Immunologic↗

PubMed1978

The first derivative of the transthoracic electrical impedance as an index of changes in myocardial contractility in the intact anaesthetised dog.

The suitability of the peak value of the first derivative of the thoracic electrical impedance dZ/dtmax has been investigated in dogs as a non-invasive index of changes in myocardial contracility by comparing if with the peak left ventricular dP/dt and the peak values of aortic blood velocity and acceleration. An increase in the inspired halothane concentration was used to produce changes in contracility. In 5 dogs the combined values for the correlation coefficient between dZ/dtmax peak velocity and acceleration were respectively 0.937, 0.954 and 0.950. In 14 out 15 comparisons p less than 0.001 and in one, p less than 0.01. On these grounds, dZ/dt max is proposed as a variable worthy of sconsideration in patient monitoring.

Animals↗

PubMed1977