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Biomedical subjects

A Johns

Publications and source records attributed to A Johns.

At least 19 recordsLinked to original sources
PubMed1996

Disruption of estrogen receptor gene prevents 17 beta estradiol-induced angiogenesis in transgenic mice.

Estrogen is known to modulate angiogenesis, both under physiological and pathological conditions, and has been demonstrated to augment angiogenesis induced by bFGF in a mouse model. We have modified this mouse model and measured the apparent plasma volume in Matrigel plugs containing basic fibroblast growth factor (bFGF) in wild type and estrogen receptor knockout, ovariectomized mice in the presence and absence of exogenous 17 beta estradiol. The apparent plasma volume was determined by measuring the fluorescence of the excised plug 10 min. after injection of fluoroscein labeled dextran 150. In wild type mice exogenous 17 beta estradiol increased the apparent plasma volume of the Matrigel plug and the uterine weight significantly. In the estrogen receptor knockout mice exogenous 17 beta estradiol caused a small, but significant increase in uterine weight but was without effect on the apparent plasma volume of the Matrigel plug. It is concluded that functional estrogen receptors are essential for the augmentation of bFGF-induced angiogenesis by exogenous 17 beta estradiol in female mice.

Animals↗
PubMed1996

Aromatase expression in endometriosis.

The conversion of C19 steroids to estrogens occurs in a number of tissues, such as the ovary and placenta, and is catalyzed by aromatase P450 (P450arom; the product of the CYP19 gene). P450arom expression has also been detected in a number of uterine tumors, such as leiomyomas and endometrial cancer. On the other hand, P450arom expression was undetectable in normal endometrial and myometrial tissues. The present study was conducted to determine the presence or absence of aromatase expression in peritoneal endometriotic implants and in the eutopic endometrium of women with endometriosis. Endometriotic implants in pelvic peritoneum (n = 17; e.g. posterior culdesac, bladder, and anterior culdesac) and eutopic endometrial curettings (n = 11) of 14 patients with histologically documented pelvic endometriosis were obtained at the time of laparoscopy or laparotomy. Pelvic peritoneal biopsies distal to endometriotic implants as well as normal endometrial tissues (n = 7) from disease-free women were used as negative controls. We used competitive RT-PCR technology employing an internal standard to amplify P450arom transcripts in total ribonucleic acid (RNA) isolated from these tissues. P450arom transcripts were detected in all endometriotic implants and in all eutopic endometrial tissues from patients with endometriosis. P450arom messenger RNA species were not detectable in endometrial tissues from disease-free women or in endometriosis-free peritoneal tissues. The highest levels of transcripts were detected in an endometriotic implant that involved the full thickness of the anterior abdominal wall. The P450arom transcript level within the core of this endometriotic mass was 4-fold higher than that in the surrounding adipose tissue. It has been shown recently that aromatase expression in various human tissues is regulated by the use of tissue-specific promoters via alternative splicing. To analyze promoter usage, we amplified by RT-PCR the most likely promoter-specific untranslated 5'-termini of P450arom transcripts in 2 endometriotic implants. It appears that these endometriotic implants use both the adipose-type promoter I.4 and gonadal-type promoter II for aromatase expression. The use of promoter I.4 for aromatase expression in adipose tissue has been recently observed to be regulated by members of the interleukin-6 (IL-6) cytokine family. Based on these findings, we examined by RT-PCR, IL-6 and IL-11 messenger RNA expression in 5 endometriotic tissues and 1 eutopic endometrial sample from a patient with endometriosis. We detected IL-6 and IL-11 transcripts in all endometriotic tissues and in the eutopic endometrial tissue sample studied. Our findings indicate that both eutopic endometrial tissues and endometriotic implants from patients with endometriosis are biochemically different from normal endometrial tissues of disease-free women. The presence of aromatase expression in eutopic endometrial tissues from patients with endometriosis may be related to the capability of implantation of these tissues on peritoneal surfaces. Furthermore, the possibility of estrogen production in these implants may serve to promote their growth. Increased IL-6 and IL-11 expression in these tissues suggests that P450arom expression in endometriosis may be regulated in part by these cytokines.

Adult↗
PubMed1995

Endothelium derived relaxing factor release from canine coronary artery by leukocytes.

Lectins, known to recognize endothelial cell adhesion molecules, have been shown to release endothelium-derived relaxing factor (EDRF) from blood vessels. We investigated the effects of different leukocyte-type cells to determine if these cells, by interacting with the endothelium, could release EDRF from the circumflex branch of the canine coronary artery. The following cells were investigated: human promyelocytic leukemia (HL-60), human monocyte (THP-1), and human Burkitt lymphoma (DAUDI). All of these cells produced a significant endothelium-dependent relaxation of the dog coronary artery in the presence of ibuprofen. The endothelium-dependent relaxations were reversed by hemoglobin (10 microM), methylene blue (3 microM), 6-anilino-5,8-quinolinedione (LY 83583, 30 microM), and NG-nitro-L-arginine methyl ester (L-NAME, 1 mM). HL-60 cells grown in the presence of 1 mM L-NAME retained their ability to cause endothelium-dependent relaxation of the canine coronary artery, suggesting that the source of the NO was the endothelium and not the HL-60 cells. The cell-induced vascular relaxation could be obtained in the absence of extracellular calcium. It is suggested that HL-60, THP-1, and DAUDI cells interact with a specific receptor on the endothelial cell and as a result of this interaction the endothelial cells are stimulated to release EDRF.

Aminoquinolines↗
PubMed1994

Constitutive endothelin-1 overexpression promotes smooth muscle cell proliferation via an external autocrine loop.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide originally purified from endothelial cell-conditioned medium. It has multiple biological activities and has been implicated in a number of human diseases, including hypertension and atherosclerosis. Contradictory reports have been published regarding whether ET-1 is a mitogen for vascular smooth muscle cells (SMC); thus, this issue is presently unresolved. In this study, we demonstrate that rat aortic SMC express functional endothelin cell surface receptors but do not proliferate when ET-1 is added to serum-free culture medium on every other day for a period of 1 week. To determine whether ET-1 could function in an autocrine manner to promote SMC growth, we transfected this same cell line with an ET-1 expression plasmid. Several independent lines expressing variable levels of ET-1 mRNA and biologically active ET-1 were obtained. Cell proliferation assays indicated that the transfected SMC line secreting the highest level of ET-1 had an enhanced growth rate when compared with untransfected or vector-alone transfected cells. The growth rate of this SMC line, but not of untransfected cells, was significantly reduced when the ETA receptor subtype-selective antagonist BQ-123 was included in the culture medium. These results indicate that constitutive ET-1 overexpression can promote SMC proliferation. Therefore, it is possible that under certain conditions ET-1 could be an important factor controlling SMC replication in vivo.

Animals↗
PubMed1994

Opiate treatments.

One of the greatest of challenges facing medicine is to devise effective and appropriate treatments for opiate problems. Such treatments are based on principles derived from the disciplines of pharmacology and psychology, but are also shaped by social issues and even by the views of practitioners. There are many misconceptions about opiate problems. In this review it is suggested that there are good reasons for stating that opiate users do change over time, treatment can also lead to change and psychological interventions are of great importance. However, current methods of opiate detoxification are of low efficacy and methadone maintenance, although of benefit for some, is not a panacea for opiate problems.

Combined Modality Therapy↗
PubMed1994

Phenol red is a thromboxane A2/prostaglandin H2 receptor antagonist in canine lingual arteries and human platelets.

Phenol red (PR) is used as a pH indicator in cell culture medium. We found that cell culture medium containing PR relaxed canine lingual arteries (LA) contracted by the thromboxane A2/prostaglandin endoperoxide (TPE) receptor agonist (15S)-hydroxy-11-alpha-9-alpha- (epoxymethano)prosta-5Z,13E-dienoic acid (U46619). We tested the effect of PR and the TPE receptor antagonist ONO-3708 on U46619, prostaglandin F2 alpha (PGF2 alpha), phenylephrine (PE) and potassium chloride (KCl)-induced contraction of the LA and on human platelet aggregation to U46619, ADP, arachidonic acid (AA), A23187 and thrombin. U46619, PGF2 alpha, KCl and PE produced equal tension development of the LA. PR relaxed the LA contracted with U46619 and PGF2 alpha with IC50 concentrations of 18.3 +/- 10 and 37.3 +/- 8.8 microM, respectively. ONO-3708 inhibited the contractions to U46619 and PGF2 alpha with IC50 of 9.4 +/- 2.2 and 12.2 +/- 2.2 nM, respectively. However, PR (300 microM) and ONO-3708 (300 nM) did not affect contraction of the LA to KCl or PE. PR inhibited human platelet aggregation, in vitro, to AA and U46619 and second wave aggregation to ADP but did not affect thrombin or first wave ADP-mediated platelet aggregation. PR inhibited U46619 and AA-induced changes in cyclic AMP and Fura-2 calcium transients in platelets and LA. However, PR did not affect the activation of cyclic AMP or intracellular calcium ion in platelets or calcium influx and the release of intracellular calcium ion in canine LA produced by ryanodine, KCl and PE. The concentration of PR in many culture media is between 40 and 70 microM. The data support the conclusion that PR, in concentrations used as a pH indicator, is a selective antagonist of TPE receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

EDRF release from canine coronary artery by lectins.

1. The effect of wheat germ agglutinin (WGA), concanavalin A (Con A) and lentil lectin agglutinin (LCA) were investigated on pre-contracted canine coronary artery rings in vitro. 2. In endothelium-intact canine coronary artery, contracted with the thromboxane A2-analogue, U46619, WGA relaxed the tissue in a concentration-dependent manner, with an inhibitory concentration (IC50) of 112 +/- 17 nM (n = 6). In the absence of an endothelium, WGA did not cause any relaxation of the tissue. 3. In endothelium-intact canine coronary artery, contracted with the thromboxane A2-analogue, U46619. LCA relaxed the tissue in a concentration-dependent manner, with an inhibitory concentration (IC50) of 423.1 +/- 41 nM (n = 6). In the absence of an endothelium, LCA produced a 20.1 +/- 1.1% (n = 6) relaxation at the highest concentration tested (3 microM). 4. Concanavalin A (Con A) relaxed canine coronary artery in a partial endothelium-dependent manner with an IC50 of 104 +/- 19 nM on endothelium-intact coronary artery and an IC50 of 1.3 +/- 0.3 microM (n = 6) on endothelium-denuded tissues. 5. The relaxation effects of WGA were attenuated by 1 mM NG-monomethyl L-arginine (L-NMMA) and completely inhibited by haemoglobin (3 microM), methylene blue (10 microM) and LY 83583 (30 microM). Ibuprofen had no effect on WGA-induced relaxation. 6. The relaxant effects of WGA were reversed by addition of 20 mM N-acetyl-D-glucosamine (GlcNAc) and N-acetyl-D-galactosamine (Ga1NAc) but not by alpha-mannose, D-(+)-galactose, and beta-lactose, whereas the endothelin-dependent relaxations to LCA and Con A were unaffected. 7.The endothelium-dependent relaxation induced by the lectins was unaffected by pretreatment of the tissue with 1 microM atropine.8. In the absence of extracellular calcium, WGA was also able to release EDRF suggesting that WGA acts through a second messenger system to release intracellular calcium.9. We suggest that WGA acts as an agonist to release EDRF from endothelial cells possibly by binding to a sugar moiety, specific receptor or adhesion molecules on the endothelial cell surface.

Animals↗
PubMed1993

Cocaine in the UK--1991.

More than 100 years after Freud's original endorsement of the drug, the use of cocaine is a problem for both users and for society, which struggles to organise effective responses to the epidemic of the last decade. During the 1980s the rapid spread of smokeable cocaine (including 'crack') was seen in the Americas (particularly the US). The initial simple predictions of an identical European epidemic were mistaken. The available data on the extent of cocaine use and of cocaine problems in the UK are examined. New forms of cocaine have been developed by black-market entrepreneurs ('freebase' and 'crack'), and new technologies have emerged for their use; with these new technologies have come new effects and new problems. The general psychiatrist now needs a knowledge of directly and indirectly related psychopathology which has an increasing relevance to the diagnosis and management of the younger patient.

Cocaine↗