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Biomedical subjects

J Fontana

Publications and source records attributed to J Fontana.

17 recordsLinked to original sources
PubMed1999

Regulation of endothelium-derived nitric oxide production by the protein kinase Akt.

Endothelial nitric oxide synthase (eNOS) is the nitric oxide synthase isoform responsible for maintaining systemic blood pressure, vascular remodelling and angiogenesis. eNOS is phosphorylated in response to various forms of cellular stimulation, but the role of phosphorylation in the regulation of nitric oxide (NO) production and the kinase(s) responsible are not known. Here we show that the serine/threonine protein kinase Akt (protein kinase B) can directly phosphorylate eNOS on serine 1179 and activate the enzyme, leading to NO production, whereas mutant eNOS (S1179A) is resistant to phosphorylation and activation by Akt. Moreover, using adenovirus-mediated gene transfer, activated Akt increases basal NO release from endothelial cells, and activation-deficient Akt attenuates NO production stimulated by vascular endothelial growth factor. Thus, eNOS is a newly described Akt substrate linking signal transduction by Akt to the release of the gaseous second messenger NO.

Animals↗
PubMed1999

ICAM-1 and CD11b inhibition worsen outcome in rats with E. coli pneumonia.

We investigated whether inhibiting an endothelial adhesion molecule [intracellular adhesion molecule 1 (ICAM-1)] would alter outcome and lung injury in a similar fashion to inhibition of a leukocyte adhesion molecule (integrin CD11b) in a rat model of gram-negative pneumonia. Inhibition of ICAM-1 with monoclonal antibody (MAb) 1A29 (1 mg/kg sc or 0.2 or 2 mg/kg iv, q 12 h x 3) or of CD11b with MAb 1B6 (1 mg/kg sc, q 12 h x 3) were compared against similarly administered placebo proteins in rats challenged with intrabronchial Escherichia coli. After challenge, all animals were treated with antibiotics. ICAM-1 MAb (6 mg/kg, iv, total dose) increased mortality vs. control (P = 0.03). CD11b MAb (3 mg/kg, sc, total dose) did not significantly (P = 0.16) increase mortality rates, but this was not in a range of probability to exclude a harmful effect. All other doses of MAb had no significant effect on survival rates. ICAM-1 and CD11b MAbs had significantly different effects on the time course of lung injury, circulating white cells and lymphocytes, and lung lavage white cells and neutrophils (P = 0.04-0.003). CD11b MAb decreased, whereas ICAM-1 MAb increased these measures compared with control from 6 to 12 h after E. coli. However, from 144 to 168 h after E. coli both MAbs increased these measures compared with control rats but to a greater level with CD11b MAb. Thus both ICAM-1 and CD11b appear to be necessary for survival during E. coli pneumonia. Although these adhesion molecules may participate differently in early lung injury, with CD11b increasing and ICAM-1 decreasing inflammation and injury, both are important for the resolution of later injury. During gram-negative pneumonia the protective roles of ICAM-1 and CD11b may make their therapeutic inhibition difficult.

Animals↗
PubMed1998

Antagonistic effects of ABL and BCRABL proteins on proliferation and the response to genotoxic stress in normal and leukemic myeloid cells.

Following the discovery of the p210bcrabl protein product of the bcrabl chimeric fusion gene generated by the Philadelphia chromosome translocation in chronic myelogenous leukemia (CML), structure function studies quickly identified which parts of this molecule were playing a role in the generation of the phenotypes of growth factor independent growth, anchorage independent growth, and genetic instability which are associated with this disease. These latter changes result in abnormally high levels of mature myeloid elements circulating in the systemic circulation of CML patients. In addition, the genetic instability which is associated with the presence of the Philadelphia chromosome drives the evolution of the disease from an indolent chronic non life-threatening leukemia, to a fulminant acute leukemic syndrome which results in the death of patients from bleeding and infection. Multiple sites of contact between the p210bcrabl and its substrates have already been identified which are relevant to the phenotypic changes characteristic of CML cells and define their response to therapy. In this review, we will discuss what is known about the relationships between the structural domains of the p210bcrabl protein and the characteristics of the disease process which it causes. We will also discuss how this information may be applied to the establishment of new directions in therapy.

Cell Differentiation↗
PubMed1992

Anomalous origin of left coronary artery from the pulmonary artery: evolution of left ventricular function and perfusion after surgery in a 44-year-old man.

Anomalous origin of left coronary vessel from the pulmonary artery is an almost universally fatal form of congenital heart disease unless appropriate corrective surgery is performed at an early age. A case was diagnosed in a symptomatic 44-year-old man who presented an impairment of systolic left ventricular function. The abnormality was successfully treated with ligation of the left coronary artery combined with left internal mammary artery anastomosis. Left ventricular function improved dramatically six months after surgery, both at rest and during exercise. Such an evolution suggests that surgery may be indicated not only in infants but also in adults with this congenital heart abnormality.

Adult↗
PubMed1988

A prospective randomized trial of HLA-matched versus mismatched single-donor platelet transfusions in cancer patients.

The use of histocompatability antigen (HLA)-matched platelets has been advocated for the support of thrombocytopenic cancer patients. We randomized 78 newly diagnosed cancer patients prospectively (before thrombocytopenia) to receive either HLA-matched or mismatched single-donor platelet transfusions. Three hundred forty-one platelet transfusions were given for 80 separate episodes of therapy-induced thrombocytopenia in 33 patients. Forty-five patients receiving intensive chemotherapy did not develop significant (less than 20,000 platelets/mm3) thrombocytopenia and did not receive a platelet transfusion. No marked difference was observed between the matched and mismatched groups in regard to number of total platelet transfusions per patient (median, 3 vs. 5, respectively; P = 0.076), number of platelet transfusions per episode (median, 3.0 vs. 3.5, respectively; P = 0.28), or days between transfusions (median, 2 vs. 2, respectively, P greater than 0.4). Bleeding episodes, although rare, tended to be of increased severity in the mismatched group. Febrile patients receiving mismatched platelets tended to have a lower posttransfusion increment increase than their nonfebrile counterparts (P = 0.068), although a similar trend could not be demonstrated between febrile and nonfebrile patients who received matched platelets (P = 0.22). Patients treated as outpatients had significantly higher posttransfusion increments than when transfused as inpatients when they were given mismatched platelets (P less than 0.0005). Development of antiplatelet antibody did not appear to affect response to platelet transfusions. Only one patient developed sustained high-level antibody titers. In patients where thrombocytopenia was significant, the transfusion of HLA-matched platelets did not appear to offer a significant advantage. However, HLA-matched platelet transfusions tended to be associated with higher posttransfusion increments in febrile patients and a trend toward fewer severe bleeding episodes. A multi-institution trial containing a large number of patients is needed to evaluate trends observed in this study.

Adolescent↗
PubMed1987

Histiocytosis X and acute monocytic leukemia. Biologic illustration of the monocyte phagocytic system.

The concept of a mononuclear phagocytic system consisting of a continuum of cells arising from the bone marrow monoblast and terminating in the mature tissue macrophage is being actively investigated. The presentation of documented acute monocytic leukemia 18 months following the confirmed diagnosis of histiocytosis X in a 39-year-old man strongly supports the concept of the mononuclear phagocytic system lineage.

Adult↗
PubMed1987

Elevation of adenylate cyclase activity during leukemic cell differentiation.

Exposure of the various human myeloid leukemic cell lines (HL60 and RDFD) to various compounds results in marked differentiation of the cells. This differentiation is associated with a marked increase in both basal and NaF-stimulated adenylate cyclase (AC) activity. The increase in AC activity occurs regardless of the differentiation inducer one has utilized (retinoic acid (RA), dimethyl formamide (DMF), hypoxanthine (HPX) or actinomycin D (actD) and is correlated with this process, as a variant of the HL60 cell (HL60-Blast) that does not differentiate upon exposure to the various inducers does not demonstrate this increase in AC activity. In addition, the differentiation process is associated with a rapid increase in intracellular cAMP within hours of adding the inducer, followed by a gradual decrease.

Adenylyl Cyclases↗
PubMed1985

Potentiation between intracellular cyclic-AMP-elevating agents and inducers of leukemic cell differentiation.

Acute leukemia is the result of a defect in the process of normal cellular differentiation. Human leukemia cell lines (HL60, RDFD-2) have been established which can be induced to differentiate into phenotypically mature cells by a variety of agents. Recent evidence suggests that cyclic adenosine 3'-5'-monophosphate (cAMP) and the cAMP dependent protein kinase (cAMP-dPK) may be intimately involved in myeloid differentiation. The addition of low levels of a wide variety of inducers of a diverse chemical nature, dimethylformamide (DMF), retinoic acid (RA), actinomycin D (ACT-D) or hypoxanthine (HPX) prior to the addition of 8-bromo-cyclic adenosine 3'-5' monophosphate (8-Br-cAMP), cholera toxin (CT) or the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) results in marked potentiation of differentiation of both HL60 and RDFD cells as manifested by the acquisition of the antigen OKM-1, the ability to reduce nitroblue tetrazolium or expression of the chemotactic receptor. Potentiation of differentiation is also observed when 8-Br-cAMP, CT or IBMX is added prior to the addition of either RA, DMF, ACT-D or HPX. These results suggest a role for cAMP in myeloid differentiation.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Phase II study of vindesine in patients with advanced breast cancer.

Vindesine, a new vinca alkaloid, was administered to 20 patients with advanced refractory breast cancer in a phase II trial. The drug was given at a dose of 3 mg/m2 by iv bolus each week for 6 consecutive weeks, and responding patients were maintained on a dose of 4 mg/m2 every 2 weeks. Nineteen patients were evaluable for disease response; partial remissions were obtained in five patients, for a response rate of 26%. Leukopenia was the major dose-limiting toxic reaction, but most patients were able to tolerate this schedule without difficulty. Neurotoxicity was mild and did not require dose reduction.

Aged↗
PubMed1980

Expression of human alpha-globin genes in hybrid mouse erythroleukaemia cells depends on differentiated state of human donor cell.

We have developed a system which can be used to study the mechanisms that may govern the expression of human alpha-globin genes in human erythroid and non-erythroid haematopoietic cells. Human chromosome 16, which has been shown to bear the human alpha-globin genes, is introduced by cell fusion into mouse erythroleukemia (MEL) cells to generate continuously proliferating cell lines that retain permanently the human alpha-globin genes. We have shown that hybrid diploid MEL cells with human alpha-globin genes from erythroid donor cells express these genes fully through globin chain synthesis, while hybrid diploid MEL cells containing human alpha-globin genes from non-erythroid human haematopoietic donor cells contain very low levels of human alpha-globin mRNA and no detectable human alpha-globin chains. The levels of human alpha-globin mRNA in these hybrid cells were found to depend on factors present in the MEL recipient cell as well as on the differentiated state of the human donor cell, suggesting that this system may be suitable for characterisation of mechanisms governing haematopoietic differentiation in man.

Animals↗
PubMed1975

Prostaglandin levels in endometrial jet wash specimens in patients with dysmenorrhea before and after indomethacin therapy.

A patient with functional primary dysmenorrhea of over two years duration was subjected to the endometrial jet wash technique during the period of active menstrual flow. Prostaglandin F analysis of the jet washings revealed significantly elevated levels during menstruation over normal control levels. Following indomethacin therapy, jet wash prostaglandin F levels were dramatically reduced and the patient became asymptomatic. A cause and effect relationsship between prostaglandin F and dysmenorrhea is suggested by these studied.

Adult↗
PubMed1975

Prostaglandin F levels in endometrial jet wash specimens during the normal human menstrual cycle.

The Gravlee endometrial jet wash technique has been used to collect uterine fluid in normal human volunteers for Prostaglandin F analysis throughout the human menstrual cycle. Uterine washings so obtained demonstrated a cyclicity in prostaglandin F content with low concentrations found during the proliferative phase and a 3-4 fold rise occurring during the secretory phase. Menstrual fluid prostaglandin F content collected with the jet wash technique gave the highest total concentrations.

Adult↗
PubMed1970

Superfetation.

Explore the source record for details and available documents.

Adult↗
PubMedDate not supplied

Acute meningoradiculitis concomitant with seroconversion to human immunodeficiency virus type 1.

We report a case of acute regressive meningoradiculitis concomitant with HIV1 primoinfection. The clinical symptoms were mild and disappeared spontaneously. Electromyographic studies confirmed the regressive demyelinating-type process. The biological diagnosis of HIV1 infection was demonstrated by viral antigen detection, by the presence of the integrated proviral DNA after gene amplification by a polymerase chain reaction, and in particular, by the steady progression in the appearance of different HIV1-specific antibodies. This was shown using three different Western blot kits whose performances were compared.

Acute Disease↗