Search PubMed⌕ Search

Biomedical subjects

E M Gordon

Publications and source records attributed to E M Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1994

Gene therapy using retroviral vectors.

Gene therapy is a novel approach for treating various congenital and acquired genetic disorders, including cancer, heart disease, and acquired immune deficiency syndrome. Amongst possible gene delivery systems, retroviral vector mediated gene transfer has been the most extensively studied and has been approved for use in over 40 current Phase I/II clinical trials for the treatment of various disorders, primarily cancers. Recent technological improvements include the optimization of vector production by concentration and lyophilization, resulting in high titers of vectors, as well as the large-scale production of vector-produced cells for the treatment of brain cancer. Present clinical protocols require specialized care centers with expertise in molecular biology and cell transplantation. Considerable effort is under way to develop retroviral vectors that can be both injected directly into the body and targeted to specific cell types within the body. Such vectors could be administered to patients by physicians in their offices. Successful development of this new technology would greatly expand the clinical potential of gene therapy.

Animals↗
PubMed1994

The Mitrofanoff principle for urethral failure.

OBJECTIVE: To assess the outcome of surgery for urethral failure. PATIENTS AND METHODS: Patients undergoing lower urinary tract reconstruction are recorded prospectively by protocol. Thirty-four are presented whose urethra had failed as a conduit; in 23 the urethra was incontinent and in 11 it was spastic causing chronic retention. The incontinent patients had failed a variety of reconstructions, in five including insertion of an artificial sphincter. Those with chronic retention were unable to self-catheterize the urethra. RESULTS: A continent supra-public diversion using the Mitrofanoff principle was performed. In two patients a new technique was used in which a detrusor tube formed the continent conduit. Ninety-four per cent of patients were continent. Two patients voided to completion, the remainder emptied by self-catheterization. Five minor revisions were required to allow easy catheterization. There was one death. The complication rate was 17%. CONCLUSION: This type of reconstruction is preferable to the formation of an ileal conduit in this difficult group of patients.

Adolescent↗
PubMed1993

Lipophilic 1,1-bisphosphonates are potent squalene synthase inhibitors and orally active cholesterol lowering agents in vivo.

Squalene synthase catalyzes the reductive dimerization of two molecules of farnesyl diphosphate to form squalene at the final branchpoint of the cholesterol biosynthetic pathway. We report herein that isoprenyl 1,1-bisphosphonates and related analogs are potent inhibitors of rat microsomal squalene synthase (I50 = 0.7-32 nM). In addition, members of this family are potent inhibitors of cholesterol biosynthesis in rats on intravenous and oral dosing, as well as cholesterol lowering agents in rats and hamsters. Significant inhibition of cholesterol biosynthesis in rats by lovastatin occurs with a concomitant inhibition of dolichol and coenzyme-Q9 synthesis. In contrast, bisphosphonate 4 has no effect on dolichol and coenzyme-Q9 biosynthesis in rats under conditions where cholesterol biosynthesis is > 90% inhibited.

Administration, Oral↗
PubMed1993

Lingual hemorrhage in a patient with hemophilia A complicated by a high titer inhibitor. Management by continuous infusion of monoclonal antibody-purified factor VIII.

PURPOSE: The management of oral bleeding in hemophilia A patients with high titer inhibitors can be challenging. Simultaneous administration of activated prothrombin complex concentrates and antifibrinolytic agents is potentially dangerous because both agents have thrombogenic properties. We report sustained control of life-threatening lingual hemorrhage in a hemophilic patient with a high titer inhibitor (100 Bethesda Units/ml) on continuous infusion of a monoclonal antibody-purified factor VIII concentrate (75 U/kg/h). METHODS AND RESULTS: In vivo hemostasis was achieved without an initial increment in free plasma factor VIII:C. The biphasic nature of recovered factor VIII:C indicated initial antigen-antibody formation, a saturation point, then a rapid rise of free factor VIII in plasma. In vitro, rapid loss of factor VIII activity was noted in mixtures of patient's plasma and purified factor VIII during incubation at 37 degrees C. When an excess of purified factor VIII was added to patient's plasma, a plateau of stable residual factor VIII activity followed the initial loss of factor VIII activity, suggesting a second-order reaction. CONCLUSION: This type I kinetic response is typical of alloantibodies induced by exposure to factor VIII concentrates.

Aminocaproic Acid↗
PubMed1993

Expression of coagulation factor IX (Christmas factor) in human hepatoma (HepG2) cell cultures after retroviral vector-mediated transfer.

PURPOSE: In this study, we compared production of recombinant human factor IX by HepG2 cells transduced with a cytomegalovirus (CMV) promoter-controlled factor IX vector to endogenous production of factor IX by non-transduced primary rat hepatocytes. METHODS AND RESULTS: Northern analysis showed 2.8 kb transcripts corresponding to the known size of factor IX mRNA in primary hepatocyte preparations and vector factor IX transcripts of the expected sizes in transduced HepG2 cell preparations. Factor IX produced by transduced HepG2 cells was completely inhibited by a monospecific antibody against human factor IX. Western analysis showed that recombinant factor IX migrated to the region of native plasma factor IX at 56 Kd. Production of biologically active factor IX by transduced HepG2 cells was 20-fold greater than that by nontransduced primary hepatocytes. CONCLUSION: These data indicate that transduced HepG2 cells transcribe, synthesize, and secrete authentic factor IX, and that these genetically engineered cells secrete significantly greater amounts of factor IX than do nontransduced primary hepatocytes. Studies are in progress to determine the effect of hepatocyte mitogens on production of factor IX in transduced HepG2 cells and primary hepatocytes.

Animals↗
PubMed1993

Superficial bladder cancer: timing of check cystoscopies in the first year.

We report a prospective study of 141 patients presenting for the first time with a small, solitary, non-invasive, moderately or well differentiated transitional cell carcinoma of the bladder. The pattern of recurrence in the first year was assessed and recurrence rates calculated; 80% of patients without recurrence at 3 months remained clear in the first year. There was a highly significant reduction in recurrence rates for those free of recurrence at 3 months. It has been suggested that this group should have the second check cystoscopy at 1 year and yearly cystoscopies thereafter. Our findings support that proposal.

Adult↗
PubMed1993

Prostatic sarcoidosis. Review of genitourinary sarcoidosis.

Sarcoidosis is seen by the urologist only rarely but it may present a diagnostic and therapeutic dilemma. We describe a rare case of prostatic sarcoidosis. The literature relating to sarcoidosis throughout the genitourinary system is reviewed.

Adult↗
PubMed1991

Mitogenic effects of coagulation factor XII and factor XIIa on HepG2 cells.

The structure of coagulation factor XII (Hageman factor), inferred from its DNA sequence, includes two epidermal growth factor (EGF)-homologous domains in its amino-terminal region. This suggests that factor XII may exhibit EGF-like activities. Reciprocal antigenic cross-reactivity between factor XII and EGF was shown by exposing purified human factor XII or mouse EGF to anti-mouse EGF or anti-human factor XII. Western blot analysis showed that anti-mouse EGF recognized intact factor XII at 80 kDa. Together, these results suggest that the EGF-homologous domains are accessible for anti-EGF binding in native factor XII. To determine whether factor XII has mitogenic activity, HepG2 or L cells (10(4) cells per well) were grown in serum-free medium in the presence or absence of factor XII or kaolin-activated factor XII (factor XIIa). Both factors XII and XIIa (6.0 micrograms/ml) enhanced cell proliferation by approximately 2-fold (P less than 0.001 and P less than 0.005, respectively). In contrast, L cells, which are not EGF target cells, were not affected by either factor XII or factor XIIa. Various doses of factor XII enhanced cell proliferation, [3H]thymidine incorporation, and [3H]leucine incorporation in HepG2 cells cultured under the same conditions. These data indicate that factor XII, like EGF, is a mitogen for HepG2 cells and suggest a possible autocrine role in the liver.

Antibodies↗
PubMed1991

Phosphorus-containing inhibitors of HMG-CoA reductase. 2. Synthesis and biological activities of a series of substituted pyridines containing a hydroxyphosphinyl moiety.

A series of 2,3,4,(5),6-substituted pyridines containing a hydroxyphosphinyl functionally have been prepared and were evaluated for their ability to inhibit the enzyme HMG-CoA reductase. Systematic substitution of both R1-R4 and X-Y led to compounds of type 3-6 with in vitro potency greater than that of mevinolin (Na salt).

Animals↗
PubMed1991

Enhanced expression of factor XII (Hageman factor) in isolated livers of estrogen- and prolactin-treated rats.

Estrogens and prolactin may raise the plasma titer of factor XII (Hageman factor) by enhancing gene expression at the level of transcription and RNA processing, protein synthesis, or secretion (or a combination of these). Alternatively, these hormones may protect factor XII or its transcripts from degradation. Because the liver is a major site of factor XII synthesis, we studied the expression and metabolism of factor XII in isolated livers of estrogen- and prolactin-treated rats. All rats were ovariectomized to reduce the effect of endogenous estrogen and prolactin on the expression of factor XII. When a phosphorus 32-labeled factor XII complementary DNA probe for Northern blot analysis was used, increased factor XII messenger RNA was found in poly (A) RNA prepared from livers of estrogen- and prolactin-treated rats relative to those of untreated rats. Simultaneously, enhanced release of immunoreactive factor XII was noted when isolated liver perfusion techniques were used. Cycloheximide, an inhibitor of protein synthesis, blocked the hepatic release of immunoreactive factor XII in both hormone-treated and untreated rats, suggesting that factor XII translation was directly affected. The biologic half-life of injected rat iodine 125-labeled factor XII in estradiol- and prolactin-treated rats was not significantly different from that in untreated rats. By inference from these data, the high plasma titer of factor XII observed in estrogen- and prolactin-treated rats is caused by enhanced hepatic expression at both transcriptional and translational levels, as well as by increased secretion of factor XII.

Animals↗
PubMed1990

Hepatocytes express blood coagulation factor XII (Hageman factor).

The liver synthesizes blood coagulation factor XII (Hageman factor). The specific cell that expresses factor XII, however, has not been previously identified. We used primary rat hepatocytes cultured in serum-free medium to study the transcription, de novo synthesis, and secretion of factor XII. A 32P-labeled human factor XII complementary DNA probe was used for RNA blot hybridization. A single band of hybridization at 2.4 kilobases appeared in blots of polyadenylated RNA derived from 24-hour hepatocyte cultures. This corresponds to the known size of factor XII-processed primary transcript (messenger RNA). Cultured hepatocytes secreted labeled factor XII when tritiated leucine was added to the medium, indicating that the hepatocytes used 3H-leucine to synthesize factor XII de novo. In these hepatocyte cultures immunoreactive factor XII levels progressively increased in 24 hours and factor XII clotting activity increased in parallel. Cycloheximide inhibited the accumulation of both immunoreactive and coagulant factor XII. Secreted factor XII from the rat hepatocytes comigrated with authentic rat plasma factor XII at 80,000 molecular weight in a Western immunoblot. These data indicate that cultured hepatocytes transcribe, synthesize, and secrete authentic factor XII.

Animals↗
PubMed1988

Altered amount and activity of superoxide dismutase in sickle cell anemia.

The amount and activity of superoxide dismutase (SOD) (EC 1.15.1.1) were measured in red cells collected from 50 white controls, 101 black controls, 50 patients with sickle hemoglobin (SS Hb), 12 with sickle trait, and 11 with other sickling hemoglobinopathies. Red cells from normal black subjects had more SOD amount and activity than normal whites (1.77 U/mg Hb and 2.96 micrograms/mg Hb vs. 1.47 U/mg Hb and 2.64 micrograms/mg Hb, respectively) or blacks with SS Hb or other sickling hemoglobinopathies. Patients with more severe manifestations of SS Hb had lower levels of SOD activity than those with milder symptoms but had the same amount of enzyme protein. Individuals with sickle trait had amounts and activities of SOD comparable to black controls. An alteration in defense to free radical oxygen may play a role in the severity of symptoms experienced by patients with homozygous sickle cell disease.

Anemia, Sickle Cell↗