Biomedical subjects

E A Cohen

Publications and source records attributed to E A Cohen.

At least 19 recordsLinked to original sources

PubMed1992

Comparison of acute elastic recoil after directional coronary atherectomy versus standard balloon angioplasty.

We evaluated intraprocedural "elastic recoil" in 25 patients (22 men and 3 women) undergoing directional coronary atherectomy (DCA) of left anterior descending stenoses, and compared these with 25 temporally-matched (14 men and 11 women) patients having balloon angioplasties (PTCA). Quantitative arteriography was performed using the Coronary Measurement System (Leiden, The Netherlands), with "elastic recoil" defined as the difference in maximum device or balloon size minus residual minimum diameter. In addition, we determined the effects of relative device size, specific anatomic location (proximal/mid artery), lesion length, eccentricity (symmetry index), and dystrophic calcification on acute "recoil" severity after both procedures. Although initial coronary stenoses were similar (minimum stenotic diameter, DCA = 0.59 +/- 0.20 mm versus PTCA = 0.55 +/- 0.23 mm, p = NS), less "elastic recoil" was observed after atherectomy (DCA = 0.83 +/- 0.57 mm versus PTCA = 1.26 +/- 0.56 mm, p < 0.01), and this was confirmed by absolute recoil/maximum device size ratios (DCA = 23.5 +/- 16.0% versus PTCA = 41.6 +/- 13.8%, p < 0.01). Acute "elastic recoil" was also influenced by maximum device size/"normal" coronary artery ratios [(ratio < 0.9, DCA = 0.26 +/- 0.10 mm versus PTCA = 0.84 +/- 0.13 mm, p < 0.01); (ratio 0.9 to 1.1, DCA = 0.69 +/- 0.41 mm versus PTCA 0.75 +/- 0.32 mm, p = NS); (ratio > 1.1, DCA = 1.09 +/- 0.64 mm versus PTCA = 1.59 +/- 0.48 mm, p < 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

The role of the tnv protein and tnv RNA splicing signals in replication of HIV-1 IIIB isolates.

The requirement for tnv, a tat-env-rev fusion protein expressed by the IIIB strain of HIV-1, was tested. The expression of tnv was prevented by altering the 5' splice site that flanks the central coding exon of tnv. Mutants that carry such an altered 5' splice site replicate normally in an established T-cell line and in peripheral blood lymphocytes, demonstrating that tnv has no effect on virus replication. However, two mutants that carry an alteration in the 3' splice site of the same exon are replication defective. The 3' splice site mutations result in significant reduction in the expression of the 16-kDa tat protein and induce the expression of large amounts of a 19-kDa rev-related protein that initiates within the central coding exon of tnv. S1 nuclease analysis reveals that splicing to the central tnv exon occurs with substantially increased efficiency via the use of an alternate 3' splice site six nucleotides 3' from the mutated site. The effect of the 3' splice site mutations on viral protein expression and replication are fully reversed by a second site mutation that eliminates the alternate splice site.

Base Sequence↗

PubMed1992

Envelope glycoprotein and CD4 independence of vpu-facilitated human immunodeficiency virus type 1 capsid export.

The effect of vpu on the release of human immunodeficiency type 1 capsid proteins was examined in the presence or absence of virus-encoded envelope glycoproteins as well as in cells which constitutively express either the CD4 or CD8 protein. The results show that vpu-mediated facilitated export of capsid proteins from HeLa cells does not require expression of the envelope glycoprotein. The experiments also show that export of virus capsid proteins from HeLa cells facilitated by vpu is not affected by coexpression of either the CD4 or CD8 protein. The vpu protein acts in trans to facilitate export of virus capsid proteins from HeLa cells.

Antigens, CD↗

PubMed1992

Acute outcome of directional coronary atherectomy vs standard balloon angioplasty in de novo left anterior descending stenoses.

To assess the immediate outcome of directional coronary atherectomy (DCA) versus standard balloon angioplasty (PTCA) in de novo left anterior descending coronary stenoses, 25 consecutive atherectomies (22 men, 3 women) performed at The Toronto Hospital, between July 1990 and March 1991 were compared with 25 (14 men, 11 women) temporally matched successful angioplasties. Coronary stenoses were analyzed by quantitative arteriography, using the Coronary Measurement System (Leiden, The Netherlands), with estimation of transstenotic hemodynamics by fluid dynamic equations. Before and after procedure qualitative blood flow (TIMI criteria) was also evaluated, as was intimal haziness and coronary dissection. In comparison to PTCA, coronary atherectomy produced less residual minimum stenotic diameter (DCA, 2.75 +/- 0.55 vs PTCA, 1.70 +/- 0.44 mm, p < 0.001), and relative percent diameter stenosis (DCA, 17.9 +/- 10.7 vs PTCA, 34.4 +/- 10.7 percent, p < 0.001), with less transstenotic obstructive gradient (DCA, 0.2 +/- 0.2 vs PTCA, 1.0 +/- 1.5 mm Hg, p < 0.05), and greater estimated stenotic flow reserve (DCA, 4.86 +/- 0.15 vs PTCA, 4.50 +/- 0.48 x baseline, p < 0.05). Coronary atherectomy "normalized" TIMI flow patterns in virtually all patients (DCA, 2.96 +/- 0.20 vs PTCA, 2.72 +/- 0.45, p < 0.05), while creating less intimal haziness (DCA, 10/25 [40 percent] vs PTCA, 23/25 [92 percent], p < 0.01), and coronary dissection (DCA, 6/25 [24 percent] vs PTCA, 16/25 [64 percent], p < 0.05). Therefore, when compared with standard balloon angioplasty, DCA produces less residual stenosis, better transstenotic hemodynamics, while decreasing the frequency of coronary artery damage, in de novo left anterior descending stenoses.

Adult↗

PubMed1992

Directional coronary atherectomy at the Toronto and Mount Sinai Hospitals: report of the initial 120 procedures.

OBJECTIVE: To assess the procedural success and complication rates of the first 120 directional coronary atherectomy cases performed at two Toronto hospitals. DESIGN AND SETTING: Case series in tertiary referral centres. PATIENTS: One hundred and thirteen patients in whom 120 atherectomy procedures were attempted between July 1990 and April 1992. INTERVENTION: Directional coronary atherectomy. MAIN RESULTS: Angiographic success was obtained in 115 of 120 procedures (96%) involving 117 of 123 lesions (95%). Procedural success (angiographic success without death, myocardial infarction or coronary bypass surgery) was obtained in 110 of 120 procedures (92%). Adjunctive balloon angioplasty was required in 20 procedures (17%). There was one death at 36 h in an elderly patient who underwent an emergency procedure while in cardiogenic shock. Periprocedural non-Q wave myocardial infarction occurred in five patients. There were no Q wave myocardial infarctions. Three patients required coronary bypass surgery prior to discharge and vascular complications occurred in five patients. CONCLUSIONS: Directional coronary atherectomy can be performed with procedural success and complication rates comparable to conventional balloon angioplasty. Randomized trials are underway to determine if atherectomy results in a lower restenosis rate.

Adult↗

PubMed1990

Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study 4 years after surgery for myopia. Perk Study Group.

The Prospective Evaluation of Radial Keratotomy Study is a nine-center clinical trial of a surgical technique to reduce simple myopia by making incisions in the cornea. There were 435 patients (one eye per patient is reported) enrolled in the study with a 91% follow-up rate at 4 years after surgery. After surgery, uncorrected visual acuity was 20/40 or better in 76% of eyes. Fifty-five percent of the eyes had a refractive error within +/- 1.00 diopter; 28% were undercorrected, and 17% were overcorrected by more than 1.00 D. The width of the prediction 90% interval for the refractive change was 4.42 D, indicating a lack of predictability. The refractive error was not stable in some eyes; between 6 months and 4 years after surgery, 23% of eyes had a continued effect of the surgery of more than 1.00 D. For 323 patients with both eyes operated on, 64% stated they wore no optical correction. There were few serious complications. Eleven eyes (3%) lost two or three lines of best corrected visual acuity. Two eyes developed delayed bacterial keratitis without significant loss in best corrected visual acuity.

Adult↗

PubMed1990

Human immunodeficiency virus vpr product is a virion-associated regulatory protein.

The vpr product of the human immunodeficiency virus type 1 (HIV-1) acts in trans to accelerate virus replication and cytopathic effect in T cells. Here it is shown that the HIV-1 viral particle contains multiple copies of the vpr protein. The vpr product is the first regulatory protein of HIV-1 to be found in the virus particle. This observation raises the possibility that vpr acts to facilitate the early steps of infection before de novo viral protein synthesis occurs.

CD4 Antigens↗

PubMed1990

Identification of HIV-1 vpr product and function.

To investigate the role of vpr (viral protein R) in the replication and cytopathicity of human immunodeficiency virus type 1 (HIV-1), infectious proviruses were constructed that were isogenic except for the ability to produce the protein product of vpr. The experiments described here demonstrate that vpr encodes a 96 amino acid 15 kDa protein. The vpr product increases the rate of replication and accelerates the cytopathic effect of the virus in T cells. Vpr acts in trans to increase levels of viral protein expression. The stimulatory effect of vpr is observed to act on the HIV-1 LTR as well as on several heterologous promoters.

Cytopathogenic Effect, Viral↗

PubMed1990

The T open reading frame of human immunodeficiency virus type 1.

Sequence analysis of multiple isolates of the human immunodeficiency virus type 1 (HIV-1) reveals the existence of a conserved open reading frame, designated T, that partially overlaps the tat, rev, and vpu coding sequences. Here we show that in vitro translation of RNA derived from this region of the viral genome yields a 17 kDa fusion protein, the result of a minus one frameshift event in the overlap between the tat and T open reading frames. It is also shown that messenger RNA species accumulate in HIV-1 infection from which the 17 kDa protein can be made. These observations suggest that ribosomal frameshift events may result in the biosynthesis of viral regulatory as well as viral structural proteins.

Amino Acid Sequence↗

PubMed1989

Functional role of human immunodeficiency virus type 1 vpu.

To investigate the role of vpu in the replication and cytopathicity of human immunodeficiency virus type 1 (HIV-1), infectious proviruses were constructed that were isogenic except for the ability to produce the protein product of vpu. The vpu-encoded protein is shown to decrease the rate of syncytium formation and cell killing in infected CD4+ human T cells, to increase greatly the export of virus particles from infected cells, and to reduce the rate of accumulation of cell-associated viral proteins. The vpu protein complements in trans the defect in a vpu- HIV-1 provirus but does not affect the simian immunodeficiency virus, which lacks vpu. These observations suggest that vpu may contribute to the AIDS epidemic by increasing the transmission efficiency of the virus.

Base Sequence↗

PubMed1989

Retention and expression of the left end subfragment of the herpes simplex virus type 2 BglII N DNA fragment do not correlate with tumorigenic conversion of NIH 3T3 cells.

Cotransfection experiments have been carried out using recombinant plasmids pAG60, conferring resistance to antibiotic G418, and pXho3 which contains the left end subfragment (map coordinates 0.583 to 0.596) of the transforming herpes simplex virus type 2 BglII N DNA fragment and encodes the 36K polypeptide associated with the viral ribonucleotide reductase activity. Several NIH 3T3 cell clones resistant to G418 and having morphological changes commonly observed for transformed NIH 3T3 cells were isolated and examined for the presence and stable retention of the viral sequences. Seven of the clones that retained the transfected viral sequences were analysed for the expression of the 36K polypeptide and the tumorigenic phenotype. The results gathered from these studies show that neither the retention of the viral DNA nor the expression of the 36K polypeptide correlated with tumorigenic conversion of these cells.

Animals↗

PubMed1988

Organization of the sunflower 11S storage protein gene family.

We have isolated and characterized genes encoding the sunflower 11S globulin seed storage proteins, collectively termed helianthinin. One gene, designated HaG3, has a primary transcription unit of about 1750 nucleotides including two short intervening sequences. The predicted precursor polypeptide from HaG3 is 493 amino acids long, is rich in glutamine and other nitrogen-rich amino acids and includes the amino acid sequence NGVEETICS. This sequence is highly conserved among 11S seed storage proteins and is involved in the proteolytic processing of these polypeptides. Additional helianthinin sequences are conserved among other seed storage protein genes. Analysis of various cDNA and genomic sequences indicates helianthinins are encoded by a small gene family that includes a minimum of two divergent subfamilies.

2S Albumins, Plant↗

PubMed1988

Identification of a protein encoded by the vpu gene of HIV-1.

Human immunodeficiency virus 1 (HIV-1) is the aetiological agent of AIDS. The virus establishes lytic, latent and non-cytopathic productive infection in cells in culture. The complexity of virus-host cell interaction is reflected in the complex organization of the viral genome. In addition to the genes that encode the virion capsid and envelope proteins and the enzymes required for proviral synthesis and integration common to all retroviruses, HIV-1 is known to encode at least four additional proteins that regulate virus replication, the tat, art, sor and 3' orf proteins, as well as a protein of unknown function from the open reading frame called R. Close examination of the nucleic acid sequences of the genomes of multiple HIV isolates raised the possibility that the virus encodes a previously undetected additional protein. Here we report that HIV-1 encodes a ninth protein and that antibodies to this protein are detected in the sera of people infected with HIV-1. This protein distinguishes HIV-1 isolates from the other human and simian immunodeficiency viruses (HIV-2 and SIV) that do not have the capacity to encode a similar protein.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Mutational analysis of the 5' non-coding region of human immunodeficiency virus type 1: effects of secondary structure on translation.

The first 111 nt from the 5' end of human immunodeficiency virus type 1 (HIV-1) mRNAs are shown to have a strong inhibitory effect on the translation of mRNA in in vitro translation extracts as well as in Xenopus oocytes. Mutations in the sequence of the 5' untranslated region (UTR) designed to disrupt predicted secondary structure of this region relieve the inhibition. Inhibition is restored by mutations that reconstruct the predicted secondary structure. The accessibility of the 5'-terminal cap structure was also found to be increased by some of these mutations. We conclude that secondary structure in the 5' UTR of HIV-1 mRNAs and resultant inaccessibility of the cap structure is responsible for the inhibition of translation. The implications of these findings for the understanding of the life cycle of HIV-1 are discussed.

Animals↗

PubMed1987

Structure-activity studies on synthetic peptides inhibiting herpes simplex virus ribonucleotide reductase.

Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) ribonucleotide reductase is formed by the association of two nonidentical subunits. A peptide corresponding to the COOH terminus of the subunit 2, Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu (H2-(7-15)), has been shown to completely inhibit the reductase activity (IC50 = 36 microM) without affecting the host isoenzyme. In order to study the relationship between chemical requirements and inhibitory potencies, a series of peptides, including fragments and analogs of H2-(7-15), were synthesized. The minimum active core can be assigned to the Val-Val-Asn-Asp-Leu sequence (IC50 = 760 microM). N alpha-Extended peptides, such as Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu (H2-(4-15)) and Glu-Cys-Arg-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu (H2-(1-15) ), respectively, have inhibitory potencies 2.1- and 1.4-fold greater than the nonapeptide H2-(7-15). N alpha-Deamination or acetylation of H2-(7-15) increases its potency by 1.8- and 3.0-fold, respectively, whereas amidation of the alpha-carboxylic function diminishes its activity by 3.2-fold. These results indicate that the alpha-amino group is not essential for maximum potency but suggest that a free carboxylic function is required. Substitution of Tyr7 or Ala8 by their respective D-isomer leads to a decrease of potency, suggesting that a specific conformation of the NH2-terminal portion is required to have a maximum activity. Monosubstitution in positions 11, 13, 14, and 15, by L-alanine completely abolishes activity stressing the importance of each amino acid residue contained in the minimum active core. Finally, nonapeptides corresponding to the COOH-terminal portion of the subunit 2 of Epstein-Barr and varicella-zoster virus ribonucleotide reductases also inhibit the HSV-1 reductase activity. The varicella-zoster virus nonapeptide is 4.0 times more potent than H2-(7-15), whereas the Epstein-Barr virus nonapeptide is 3.1 times less potent. These results should help us to design a new generation of potent inhibitors of herpes virus ribonucleotide reductases.

Amino Acid Sequence↗

PubMed1987

Sequence and expression of a gene encoding an albumin storage protein in sunflower.

The complete sequence of a sunflower (Helianthus annuus) gene, HaG5, encoding a 2 S albumin storage protein was determined. The predicted unprocessed precursor has 295 amino acids, is rich in glutamine residues (24%) and contains a hydrophobic amino-terminus that is similar to the consensus signal peptide. Amino acid sequencing of the mature protein revealed extensive post-translational processing. Nuclease protection and primer extension analysis indicated a major transcriptional start 30 nucleotides 5' of the predicted ATG start codon. Additional sequence data, determined from a nearly full length cDNA recombinant, indicate that HaG5 is a member of a small gene family comprised of at least two divergent genes. Comparison of the predicted HaG5 gene product with sequences of other known plant proteins revealed distant but significant homology with the napins of Brassica and other heterogeneous seed proteins in the albumin superfamily.

2S Albumins, Plant↗

PubMed1987

Identification of viral polypeptides involved in pseudorabies virus ribonucleotide reductase activity.

We studied pseudorabies virus-induced ribonucleotide reductase and found that it exhibited biochemical properties very similar to those of herpes simplex virus reductase. A polyclonal rabbit antiserum (P9) directed against the carboxy terminus of subunit H2 polypeptide (38,000 daltons) of herpes simplex virus reductase neutralized the pseudorabies virus reductase, as well as the herpes simplex virus isozyme. This serum recognized two pseudorabies virus-specified polypeptides of 34,000 and 110,000 daltons, which may represent the two subunits of the enzyme. Furthermore, as already shown for herpes simplex virus reductase (E. A. Cohen, P. Gaudreau, P. Brazeau, and Y. Langelier, Nature [London] 321:441-443, 1986), we show that the nonapeptide itself specifically inhibited pseudorabies reductase activity.

Herpesvirus 1, Suid↗

PubMed1987

Activities of both ribonucleotide reductase subunits, M1 and M2, decrease upon serum starvation of baby hamster kidney 21/C13 cells.

Ribonucleotide reductase from mammalian cells is composed of two nonidentical subunits M1 and M2 which are both required to form the catalytic site. The level of ribonucleotide reductase activity is cell cycle controlled and several reports suggest that this control is achieved mainly by the regulation of M2 subunit synthesis. In the present study, we have found that the activities of both subunits decreased markedly upon serum starvation in the Syrian baby hamster kidney 21/C13 cell line. These decreases did not seem to be correlated with the appearance of an inhibitory factor in serum-starved cells. Quantification of the amount of the M1 subunit protein (89,000 molecular weight) by [32P]dTTP photoaffinity labelling revealed that the decrease in M1 activity was not due to variation in M1 protein level. Therefore, a posttranslational mechanism probably exists which inactivates M1 subunit when cells stay in the quiescent (G0) state and this mechanism could play an important role in the control of ribonucleotide reductase activity.

Animals↗