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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 685 records · Page 38Linked to original sources
PubMed1987

Effect of deferoxamine on DNA synthesis, DNA repair, cell proliferation, and differentiation of HL-60 cells.

The ribonucleotide reductase inhibitors deferoxamine and hydroxyurea induce monocyte-macrophage cell differentiation in the leukemic cell line HL-60 as judged by the expression of cell surface antigens, nonspecific esterase activity, and morphological changes. Treatment of HL-60 cells with deferoxamine results in inhibition of DNA synthesis and irreversible loss of colony-forming ability. In addition, both deferoxamine and hydroxyurea caused an increase in the number of DNA strand breaks in HL-60 cells. A DNA methylating agent, N-methyl-N'-nitro-N-nitrosoguanidine, also caused cellular differentiation in HL-60 cells associated with DNA strand breaks. These observations are consistent with a role for DNA damage or for inhibition of DNA synthesis and repair in the differentiation process of HL-60 cells.

Antigens, Surface↗
PubMed1987

Ordinal discrimination of ECG orthogonal features.

A rigorous mathematical analysis of Electrocardiogram (ECG) data is presented in this paper, as a decision support system for ECG interpretation. The mathematical analysis: provides a new insight to the ECG data, provides flexibility for future understanding of the heart system or the ECG, and avoids the need of measurements of parameters and the disagreement concerning the standard criteria of those parameters. The system enables compressed storage of the ECG data and an easy and accurate retrieval ability. An "ordinal straight line" method is presented for simple description of the ECG features as a combination of straight lines. A new developed discrimination method--the bisector method--is used for discrimination and classification between the normal and pathological groups. The physician's decision is based on both the physician's heuristic approach and the system's classification.

Data Collection↗
PubMed1987

Management of iron overload in the pediatric patient.

Iron overload is a major complication of long-term transfusion therapy. In the absence of treatment, the excessive iron causes diffuse organ damage, usually culminating in death from heart disease. Deferoxamine, an iron-chelating drug, removes tissue iron, prevents iron-induced organ dysfunction, and prolongs life. Proper administration of deferoxamine requires careful attention to dose, route and duration of administration, and compliance. Better chelators are needed but are unlikely to be available soon. Other methods for preventing or reducing iron accumulation involve alterations in the transfusion program or the blood product. Prevention of iron overload should improve the lives of patients with transfusion-dependent anemias and extend the usefulness of transfusion in chronic hematologic disorders.

Bloodletting↗
PubMed1987

In vitro and in vivo effects of deferoxamine in neonatal acute leukemia.

A six week old infant with acute leukemia failed to attain remission with chemotherapy. Because we previously demonstrated that the iron chelator deferoxamine (DFO) has antiproliferative properties and modulatory effects on cell differentiation, a protocol was designed for in vitro study and for clinical use in the patient. At diagnosis, blast cells were morphologically undifferentiated, had nondiagnostic cytochemistry, showed an abnormal karyotype (t[4;11]), expressed markers of B cell lineage, and demonstrated C mu gene rearrangement. Tissue culture of marrow or blood cells yielded colonies of leukemic blasts. Increasing concentrations of DFO produced a dose-dependent suppression of patient's blast colony growth in vitro, and blasts within colonies showed a marked change in surface antigen expression from lymphoid to myelomonocytic markers, became monocytic in appearance, and developed intense staining for nonspecific esterase. When DFO was given intravenously to the patient as a single agent for 48 hours, blasts no longer expressed lymphoid antigens and became strongly positive for myelomonocytic markers, identical to the in vitro findings. Intravenous DFO halted rising peripheral blood blast cell numbers and allowed a several-fold increase in normal hematopoietic progenitor colony growth. When combined with low-dose cytosine arabinoside in the treatment protocol, DFO caused striking leukemic cytoreduction. Our findings indicate that DFO has antileukemic properties by virtue of its effects on proliferation and differentiation, and they prompt further experimental and clinical studies with this agent.

Antigens, Neoplasm↗
PubMed1987

Molecular and cellular aspects of axon-glia interaction in CNS regeneration.

The relationships of neurons and non-neuronal cells are vital for the maintenance and function of neurons. Trauma alters these relationships causing proliferation of non-neuronal cells and, in adult mammalian CNS, presumably disturbs the environmental support needed for regeneration. A supportive environment can be restored by introducing a regenerating nerve to injured mammalian CNS. This response is probably due, at least in part, to diffusible substances secreted by the non-neuronal cells. We have obtained diffusible substances from either regenerating fish optic nerves or neonatal rabbit optic nerves and applied them around crushed adult rabbit optic nerves. This manipulation caused the adult nerve to show regenerative changes: a general increase of protein synthesis in the retinas; selective increase in synthesis of a few polypeptides in the retinas; sprouting from the retinas in vitro; increased viability of nerve fibers as shown by HRP staining; and the appearance of growth cones adjacent to glial limitans in the injured nerves. We termed these diffusible, active substances "Growth Associated Triggering Factors" (GATFs). In addition to the phenomena described above, the active substances (obtained in the form of media conditioned by regenerating fish optic nerve or neonatal rabbit optic nerve) caused various other changes in the injured nerve itself: acceleration of non-neuronal cell proliferation; changes in the protein pattern, e.g. an increase in a 12 kDa polypeptide which might be a second mediator in the cascade of events leading to regeneration; increased laminin immunoreactive sites in the nerve; and the acquisition of growth supportive activity in media conditioned by the implanted injured nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Efficacy and safety of intravenous terazosin in hypertensive patients. A preliminary report.

Single intravenous doses of 1, 2, and 5 mg of terazosin and placebo were administered in a randomized, double-blind, crossover fashion to 12 hypertensive adult patients. Supine and sitting blood pressures and pulse rates were monitored before and for 48 hours after drug administration. Blood and urine specimens were obtained periodically up to 48 hours after dosing; the concentration of terazosin in these samples was then determined. When compared with values before dosing, significant reductions (p less than or equal to 0.05) in supine diastolic blood pressure were observed from as early as 10 minutes after infusion of a terazosin dose and including most measurements through nine hours. From 20 minutes to five hours, most of the mean decreases in supine diastolic blood pressure following infusion of terazosin were significantly greater than those following infusion of placebo. Mean changes after terazosin administration ranged from -3 to -14 mm Hg, whereas mean changes after placebo administration ranged from +2 to -7 mm Hg. Pulse rates tended to increase slightly after terazosin administration and decrease slightly after placebo administration with few changes achieving statistical significance. The onset of the antihypertensive effect (at least a 10 percent decrease in supine diastolic blood pressure) occurred within two hours after most terazosin doses. The magnitude of the antihypertensive effect was similar at all three doses. The duration of action continued for at least six hours in 40 percent of those patients who showed a response within two hours. The peak antihypertensive effect occurred approximately four hours after administration of the terazosin dose (mean decreases of 17, 18, and 19 mm Hg after the 1-, 2-, and 5-mg doses, respectively). Adverse effects were mild. The most frequently reported side effects were headache, nasal congestion, and light-headedness. Terazosin decayed in a biexponential fashion with an elimination half-life of about 12 hours. There was no indication that nonlinear elimination occurred or that hypertensive disease influenced the disposition of the drug.

Adrenergic alpha-Antagonists↗
PubMed1986

First trimester prenatal diagnosis of congenital rubella: a laboratory investigation.

Acute primary maternal infection with rubella virus during pregnancy often, but not invariably, leads to the congenital rubella syndrome. Diagnosis by detection of virus specific IgM in the mother is not always possible, and in those cases in which IgM is detected the fetus has not necessarily also been infected. A method for direct, prenatal detection of fetal infection would allow more accurate early diagnosis of congenital rubella syndrome. In this study a case of suspected preconception rubella infection that was not referred until 14 weeks after the appearance of a rash was studied to determine whether a retrospective serological diagnosis of primary rubella could be made, and whether direct evidence of fetal infection could be obtained from a chorionic villus biopsy specimen by detecting virus specific antigens or ribonucleic acid (RNA) sequences. Monoclonal antibodies and a cloned complementary deoxyribonucleic acid probe were used successfully to detect antigens to rubella virus antigens and RNA sequences in the chorionic villus biopsy specimen, which was taken at 15 weeks' gestation. This method should serve as a new approach to the diagnosis of congenital rubella syndrome in utero.

Adult↗
PubMed1986

Actin and myosin multigene families: their expression during the formation and maturation of striated muscle.

The initial formation of skeletal muscle fibers is accompanied by the expression of muscle-type actin and myosin genes. During subsequent maturation of muscle fibers in vivo, developmental changes in the fetal/adult isoforms of these proteins occur. Skeletal muscle-specific transcripts coding for different myosin heavy chains accumulate sequentially both in vivo and in vitro. A genetic analysis demonstrates that these genes are clustered, implicating cis-acting regulatory factors. In contrast, actin and myosin light chain genes are dispersed in the mouse genome. These gene families show a different developmental "strategy": Genes expressed in adult cardiac tissue are coexpressed with the corresponding skeletal muscle sequence during fetal development. This phenomenon also occurs in adult tissue. Under conditions of cardiac overload, adult rat hearts accumulate skeletal actin mRNA and cardiac actin transcripts. In some mouse lines, a mutant cardiac actin gene locus is present. The presence of a second active upstream promoter at this locus depresses transcription of the bone fide gene, resulting in low levels of mature cardiac actin mRNA. In this situation skeletal actin gene transcripts accumulate. Genes expressed in the same fetal or adult muscle phenotype are not linked, suggesting that their coexpression is regulated by transacting factors. The promoter regions of such genes in the mouse have no common characteristics of primary structure with the exception of an E1A-type enhancer core sequence, which has a conserved 5' flanking element, seen for actin and myosin light chain genes. Reintroduction of these promoter regions into muscle cells provides a functional test for such potential regulatory sequences.

Actins↗
PubMed1986

Relative bioavailability of a new transdermal nitroglycerin delivery system.

The purpose of this study was to measure the bioavailability of nitroglycerin from a new transdermal delivery system, Nitro-Dur II, relative to that of Nitro-Dur. Twenty-four healthy male volunteers completed a two-way crossover study. Each subject randomly received Nitro-Dur (I) and Nitro-Dur II (II) for a 24-h period. Both transdermal systems had an active surface area of 20 cm2. Blood samples were collected immediately before treatment, at 0.5, 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after topical application of the units, and 30 min after the units were removed. Nitroglycerin was determined with an analytical sensitivity of 50 pg/mL using gas chromatography with electron capture detection (GC-EC). Mean steady-state concentrations of nitroglycerin were 182 and 224 pg/mL for I and II, respectively. There were no statistical differences between I and II in the pharmacokinetic parameters measured (Css, AUC, Cmax, % fluctuation). Residual nitroglycerin content was measured in each transdermal unit after application to each of the 24 volunteers. The amounts of nitroglycerin delivered by I and II were 9.78 +/- 4.11 and 10.67 +/- 4.78 mg, respectively, or approximately 10 mg in 24 h. Statistical analysis of these data using an analysis of variance indicated no significant difference between these treatments (p = 0.27). Since there were also no differences in the plasma concentrations and pharmacokinetic parameters calculated after treatment with I and II, the bioequivalence of the two delivery systems was established.

Administration, Cutaneous↗
PubMed1986

Selective protection of tubercidin toxicity by nitrobenzyl thioinosine in normal tissues but not in human neuroblastoma cells.

Tubercidin, an adenosine analogue, is toxic to human neuroblastoma cell lines, to peripheral blood mononuclear cells (PBMCs), and to myeloid colony-forming cells (CFU-C) as tested by a short-term labeled precursor uptake and by a clonogenic assay. When it was co-administered with a potent purine transport inhibitor, nitrobenzyl thioinosine (NBTI), the cytotoxic effect of tubercidin was abolished in PBMCs but not in neuroblastoma cells. Studies of nucleoside transport in neuroblastoma cells demonstrate that although [3H]NBTI binds to the plasma membrane of these cells, the transport of thymidine into the cells is only partially inhibited in the presence of excess NBTI. These data imply that neuroblastoma cells contain a nucleoside transport mechanism which is insensitive to NBTI. "Host protection" with a nucleoside transport inhibitor such as NBTI, may allow effective therapy with otherwise toxic dosages of tubercidin and other cytotoxic nucleosides in patients with neuroblastoma.

Biological Transport↗
PubMed1986

Immunological characterisation of the rubella E 1 glycoprotein. Brief report.

Three epitopes have been identified on rubella virion envelope polypeptide E 1 using monoclonal antibodies. Antibodies to two of the epitopes, E 1EP1 and E 1EP2, show both haemagglutination inhibition and neutralization activities whereas antibodies to the remaining epitope, E 1EP3, show neutralizing activity only.

Animals↗