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June 9, 1993, Vol 269, No. 22 >
ARTICLE | June 9, 1993

Molecular Targets of Gene Transfer Therapy for HIV Infection FREE

Gary L. Buchschacher, Jr, PhD
[+] Author Affiliations

Reprint requests to McArdle Laboratory for Cancer Research, University of Wisconsin, 1400 University Ave, Madison, WI 53706 (Dr Buchschacher).


JAMA. 1993;269(22):2880-2886. doi:10.1001/jama.1993.03500220066028
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Published online
Article
References

THE ACQUIRED immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), is a chronic disease primarily characterized by a decrease in CD4-positive T lymphocytes. Subsequent immune system suppression and failure lead to frequent infection by opportunistic pathogens and, oftentimes along with neoplasms or other HIV-related pathology, death of the patient. During the last 10 years, considerable progress has been made in the development of treatments for various opportunistic infections. In addition, the use of nucleoside analogs (zidovudine, dideoxyinosine, dideoxycytodine), which interfere with reverse transcription and seem to slow viral spread, has become commonplace. Although these treatments can delay disease progression,1 side effects associated with their use, and possibly the development of viral resistance to these drugs,2 may inevitably lead to treatment failure.

For these reasons, alternate therapies for HIV infection are needed. Included among the list of potential treatments is gene transfer therapy. Recent progress in ongoing clinical

REFERENCES

1 +
Volberding PA, Lagakos SW, Koch MA, et al.  Zidovudine in asymptomatic human immunodeficiency virus infection. N Engl J Med . 1990;;322:941-949.
2 +
St Clair MH, Martin JL, Tudor-Williams G, et al.  Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science . 1991;;253:1557-1559.
3 +
Miller AD.  Human gene therapy comes of age. Nature . 1992;;357:455-460.
4 +
Anderson WF.  Human gene therapy. Science . 1992;;256:808-813.
5 +
Terwilliger EF.  The accessory gene functions of the primate immunodeficiency viruses.  In: Koff WC, Wong-Staal F, Kennedy RC, eds. AIDS Research Reviews, II . New York, NY: Marcel Dekker Inc; 1992;:3-27.
6 +
Sodroski J, Rosen C, Wong-Staal F, et al.  Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science . 1985;;227:171-173.
7 +
Laspia MF, Rice AP, Mathews MB.  HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation. Cell . 1989;;59:283-292.
8 +
Berkhout B, Silverman RH, Jeang K.  Tat trans-activates the human immunodeficiency virus through a nascent RNA target. Cell . 1989;;59:273-282.
9 +
Gatignol A, Buckler-White A, Berkhout B, Jeang K.  Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR. Science . 1991;;251:1597-1600.
10 +
Marciniak RA, Garcia-Blanco MA, Sharp PA.  Identification and characterization of a HeLa nuclear protein that specifically binds to the trans-activation response (TAR) element of human immunodeficiency virus. Proc Natl Acad Sci U S A . 1990;;87:3624-3628.
11 +
Cullen BR.  The HIV-1 tat protein: an RNA sequence-specific processivity factor? Cell . 1990;; 63:655-657.
12 +
Cullen BR.  Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell . 1986;;46:973-982.
13 +
Emerman M, Vazeux R, Peden K.  The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization. Cell . 1989;; 57:1155-1165.
14 +
Felber BK, Hadzopoulou-Cladaras M, Cladaras C, Copeland T, Pavlakas GN.  Rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci U S A . 1989;;86:1495-1499.
15 +
Cochrane AW, Chen C, Rosen CA.  Specific interaction of the human immunodeficiency virus Rev protein with a structured region in the env mRNA. Proc Natl Acad Sci U S A . 1990;;87:1198-1202.
16 +
Maddon PJ, Dalgleisch AG, McDougal JS, Clapman PR, Weiss RA, Axel R.  The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell . 1986;;47:333-348.
17 +
Tateno M, Gonzalez-Scarano F, Levy J.  Human immunodeficiency virus can infect CD4-negative human fibroblastoid cells. Proc Natl Acad Sci U S A . 1989;;86:4287-4290.
18 +
Cheng-Mayer C, Rutka JT, Rosenblum ML, McHugh T, Stites DP, Levy JA.  Human immunodeficiency virus can productively infect cultured human glial cells. Proc Natl Acad Sci U S A . 1987;; 84:3526-3530.
19 +
McClure MO, Marsh M, Weiss RA.  Human immunodeficiency virus infection of CD4-bearing cells occurs by a pH-independent mechanism. EMBO J . 1988;;7:513-518.
20 +
Stein BS, Gowda SD, Lifson JD, Penhallow RC, Bensch KG, Engelman EG.  pH-independent HIV entry into CD4-positive cells via virus envelope fusion to the plasma membrane. Cell . 1987;;49:659-668.
21 +
Hu WS, Temin HM.  Retroviral recombination and reverse transcription. Science . 1990;;250:1227-1233.
22 +
Panganiban AT, Fiore D.  Ordered interstrand and intrastrand DNA transfer during reverse transcription. Science . 1988;;241:1064-1069.
23 +
Panganiban AT.  Retroviral reverse transcription and DNA integration. Semin Virol . 1990;;1: 187-194.
24 +
Cullen BR, Greene WC.  Regulatory pathways governing HIV-1 replication. Cell . 1989;;58:423-426.
25 +
Aldovini A, Young R.  Mutations of RNA and protein sequences involved in human immunodeficiency virus type 1 packaging result in production of noninfectious virus. J Virol . 1990;;64:1920-1926.
26 +
Clavel F, Orenstein JM.  A mutant of human immunodeficiency virus with reduced RNA packaging and abnormal particle morphology. J Virol . 1990;;64:5230-5234.
27 +
Lever A, Gottlinger H, Haseltine W, Sodroski J.  Identification of a sequence required for efficient packaging of human immunodeficiency virus type 1 RNA into virions. J Virol . 1989;;63:4085-4087.
28 +
Freed EO, Myers DJ, Risser R.  Mutational analysis of the cleavage sequence of the human immunodeficiency virus type 1 envelope glycoprotein precursor gp160. J Virol . 1989;;63:4670-4675.
29 +
Miller AD.  Retrovirus packaging cells. Hum Gene Ther . 1990;;1:5-14.
30 +
Rosenberg SA.  Gene therapy for cancer. JAMA . 1992;;268:2416-2419.
31 +
Thompson L.  At age 2 gene therapy enters a growth phase. Science . 1992;;258:744-746.
32 +
Rosenberg SA, Aebersold P, Cornetta K, et al.  Gene transfer into humans: immunotherapy of patients with advanced melanoma using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med . 1990;;323:570-578.
33 +
Freed EO, Delwart EL, Buchschacher GL Jr, Panganiban AT.  A mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity. Proc Natl Acad Sci USA . 1992;;89:70-74.
34 +
Helseth E, Kowalski M, Gabuzda D, Olshevsky U, Haseltine W, Sodroski J.  Rapid complementation assays measuring replicative potential of human immunodeficiency virus type 1 envelope glycoprotein mutants. J Virol . 1990;;64:2416-2420.
35 +
Page KA, Landau NR, Littman DR.  Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity. J Virol . 1990;; 64:5270-5276.
36 +
Poznansky M, Leveer A, Bergeron L, Haseltine W, Sodroski J.  Gene transfer into human lymphocytes by a defective human immunodeficiency virus type 1 vector. J Virol . 1991;;65:532-536.
37 +
Buchschacher GL Jr, Panganiban AT.  Human immunodeficiency virus vectors for inducible expression of foreign genes. J Virol . 1992;;66:2731-2739.
38 +
Harrison GS, Maxwell F, Long CJ, Rosen CA, Glode LM, Maxwell IH.  Activation of a diphtheria toxin A gene by expression of human immunodeficiency virus-1 tat and rev proteins in transfected cells. Hum Gene Ther . 1991;;2:53-60.
39 +
Rossi JJ, Elkins D, Zaia JA, Sullivan S.  Ribozymes as anti-HIV therapeutic agents: principles, applications, and problems. AIDS Res Hum Retroviruses . 1992;;8:183-189.
40 +
Warner JF, Anderson C, Laube L, et al.  Induction of HIV-specific CTL and antibody responses in mice using retroviral vector-transduced cells. AIDS Res Hum Retroviruses . 1991;;7:645-655.
41 +
Riddell SR, Greenberg PD, Overell RW, et al.  Phase I study of cellular adoptive immunotherapy using genetically modified CD8+ HIV-specific T cells for HIV seropositive patients undergoing allogeneic bone marrow transplant. Hum Gene Ther . 1992;;3:319-338.
42 +
Venkatesh LK, Arens MQ, Subramanian T, Chinnadurai G.  Selective induction of toxicity to human cells expressing human immunodeficiency virus type 1 Tat by a conditionally cytotoxic adenovirus vector. Proc Natl Acad Sci U S A . 1990;; 87:8746-8750.
43 +
Caruso M, Klatzman D.  Selective killing of CD4+ cells harboring a human immunodeficiency virus— inducible suicide gene prevents viral spread in an infected cell population. Proc Natl Acad Sci U S A . 1992;;89:182-186.
44 +
Yamaizumi ME, Mekada E, Uchida T, Okada Y.  One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell. Cell . 1978;;15: 245-250.
45 +
Harrison GS, Long CJ, Maxwell F, Glode LM, Maxwell IH.  Inhibition of HIV production in cells containing an integrated HIV-regulated diphtheria toxin A chain gene. AIDS Res Hum Retroviruses . 1992;;8:39-45.
46 +
Harrison GS, Long CJ, Curiel TJ, Maxwell F, Maxwell IH.  Inhibition of human immunodeficiency virus-1 production resulting from transduction with a retrovirus containing an HIV-regulated diphtheria toxin A chain gene. Hum Gene Ther . 1992;; 3:461-469.
47 +
Sullenger BA, Gallardo HF, Ungers GE, Gilboa E.  Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Cell . 1990;;63:601-608.
48 +
Sullenger BA, Gallardo HF, Ungers GE, Gilboa E.  Analysis of trans-acting response decoy RNA-mediated inhibition of human immunodeficiency virus type 1 transactivation. J Virol . 1991;;65:6811-6816.
49 +
Lisziewicz J, Rappaport J, Dhar R.  Tat-regulated production of multimerized TAR RNA inhibits HIV-1 gene expression. New Biologist . 1991;;3: 82-89.
50 +
Lee TC, Sullinger BA, Gallardo HF, Ungers GE, Gilboa E.  Overexpression of RRE-derived sequences inhibits HIV-1 replication in CEM cells. New Biologist . 1992;;4:66-74.
51 +
Joshi S, van Brunschot A, Asad S, van der Elst I, Read SE, Berstein A.  Inhibition of human immunodeficiency virus type 1 multiplication by antisense and sense RNA expression. J Virol . 1991;; 65:5524-5530.
52 +
Sczakiel G, Oppenlander M, Rittner K, Pawlita M.  Tat- and Rev-directed antisense RNA expression inhibits and abolishes replication of human immunodeficiency virus type 1: a temporal analysis. J Virol . 1992;;66:5576-5581.
53 +
Rhodes A, James W.  Inhibition of human immunodeficiency virus replication in cell culture by endogenously synthesized antisense RNA. J Gen Virol . 1990;;71:1965-1974.
54 +
Chatterjee S, Johnson PR, Wong KK Jr.  Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus antisense vector. Science . 1992;;258:1485-1488.
55 +
Sarver N, Cantin EM, Chang PS, et al.  Ribozymes as potential anti-HIV therapeutic agents. Science . 1990;;247:1222-1225.
56 +
Dropulic B, Lin NH, Martin MA, Jeang K.  Functional characterization of a U5 ribozyme: intracellular suppression of human immunodeficiency virus type 1 expression. J Virol . 1992;;66:1432-1441.
57 +
Weerasinghe M, Liem SE, Sabah S, Read SE, Joshi S.  Resistance to human immunodeficiency virus type 1 (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme. J Virol . 1991;;65:5531-5534.
58 +
Ojwang JO, Hampel A, Looney DJ, Wong-Staal F, Rappaport J.  Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. Proc Natl Acad Sci U S A . 1992;;89:10802-10806.
59 +
Sioud M, Drlica K.  Prevention of human immunodeficiency virus type 1 integrase expression in Escherichia coli by a ribozyme. Proc Natl Acad Sci U S A . 1991;;88:7303-7307.
60 +
Feinberg MB, Trono D.  Intracellular immunization: Trans-dominant mutants of HIV gene products as tools for the study and interruption of viral replication. AIDS Res Hum Retroviruses . 1992;;8: 1013-1022.
61 +
Green M, Ishino M, Loewenstein PM.  Mutational analysis of HIV-1 Tat minimal domain peptides: identification of trans-dominant mutants that suppress HIV-LTR—driven gene expression. Cell . 1989;;58:215-223.
62 +
Tiley LS, Brown PH, Cullen BR.  Does the human immunodeficiency virus Tat trans-activator contain a discrete activation domain? Virology . 1990;; 178:560-567.
63 +
Pearson L, Garcia J, Wu F, Modesti N, Nelson J, Gaynor R.  A transdominant tat mutant that inhibits Tat-induced gene expression from the human immunodeficiency virus long terminal repeat. Proc Natl Acad Sci U S A . 1990;;87:5079-5083.
64 +
Malim MH, Bohnlein S, Hauber J, Cullen BR.  Functional dissection of the HIV-1 Rev trans-activator—derivation of a trans-dominant repressor of Rev function. Cell . 1989;;58:205-214.
65 +
Hope TJ, Klein NP, Elder ME, Parslow TG.  Trans-dominant inhibition of human immunodeficiency virus type 1 Rev occurs through formation of inactive protein complexes. J Virol . 1992;;66:1849-1855.
66 +
Kubota S, Furuta R, Maki M, Hatanaka M.  Inhibition of human immunodeficiency virus type 1 Rev function by a Rev mutant which interferes with nuclear/nucleolar localization of Rev. J Virol . 1992;;66:2510-2513.
67 +
Trono D, Feinberg MB, Baltimore D.  HIV-1 Gag mutants can dominantly interfere with the replication of the wild-type virus. Cell . 1989;;59:113-120.
68 +
Buchschacher GL Jr, Freed EO, Panganiban AT.  Cells induced to express a human immunodeficiency virus type 1 envelope gene mutant inhibit the spread of wild-type virus. Hum Gene Ther . 1992;;3:391-397.
69 +
Miller AD.  Progress toward human gene therapy. Blood . 1990;;76:271-278.
70 +
Pantaleo G, Graziosi C, Demarest JF, et al.  HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature . 1993;;362:355-358.
71 +
Embretson J, Zupancic M, Ribas JL, et al.  Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature . 1993;;362:359-362.
72 +
Kion TA, Hoffmann GW.  Anti-HIV and anti-anti-MHC antibodies in alloimmune and autoimmune mice. Science . 1991;;253:1138-1140.
73 +
Hoffmann GW, Kion TA, Grant MD.  An idiotypic network model of AIDS immunopathogenesis. Proc Natl Acad Sci USA . 1991;;88:3060-3064.
74 +
Arthur LO, Bess JW Jr, Sowder RC II, et al.  Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines. Science . 1992;;258:1935-1938.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Volberding PA, Lagakos SW, Koch MA, et al.  Zidovudine in asymptomatic human immunodeficiency virus infection. N Engl J Med . 1990;;322:941-949.
2 +
St Clair MH, Martin JL, Tudor-Williams G, et al.  Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science . 1991;;253:1557-1559.
3 +
Miller AD.  Human gene therapy comes of age. Nature . 1992;;357:455-460.
4 +
Anderson WF.  Human gene therapy. Science . 1992;;256:808-813.
5 +
Terwilliger EF.  The accessory gene functions of the primate immunodeficiency viruses.  In: Koff WC, Wong-Staal F, Kennedy RC, eds. AIDS Research Reviews, II . New York, NY: Marcel Dekker Inc; 1992;:3-27.
6 +
Sodroski J, Rosen C, Wong-Staal F, et al.  Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science . 1985;;227:171-173.
7 +
Laspia MF, Rice AP, Mathews MB.  HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation. Cell . 1989;;59:283-292.
8 +
Berkhout B, Silverman RH, Jeang K.  Tat trans-activates the human immunodeficiency virus through a nascent RNA target. Cell . 1989;;59:273-282.
9 +
Gatignol A, Buckler-White A, Berkhout B, Jeang K.  Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR. Science . 1991;;251:1597-1600.
10 +
Marciniak RA, Garcia-Blanco MA, Sharp PA.  Identification and characterization of a HeLa nuclear protein that specifically binds to the trans-activation response (TAR) element of human immunodeficiency virus. Proc Natl Acad Sci U S A . 1990;;87:3624-3628.
11 +
Cullen BR.  The HIV-1 tat protein: an RNA sequence-specific processivity factor? Cell . 1990;; 63:655-657.
12 +
Cullen BR.  Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell . 1986;;46:973-982.
13 +
Emerman M, Vazeux R, Peden K.  The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization. Cell . 1989;; 57:1155-1165.
14 +
Felber BK, Hadzopoulou-Cladaras M, Cladaras C, Copeland T, Pavlakas GN.  Rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci U S A . 1989;;86:1495-1499.
15 +
Cochrane AW, Chen C, Rosen CA.  Specific interaction of the human immunodeficiency virus Rev protein with a structured region in the env mRNA. Proc Natl Acad Sci U S A . 1990;;87:1198-1202.
16 +
Maddon PJ, Dalgleisch AG, McDougal JS, Clapman PR, Weiss RA, Axel R.  The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell . 1986;;47:333-348.
17 +
Tateno M, Gonzalez-Scarano F, Levy J.  Human immunodeficiency virus can infect CD4-negative human fibroblastoid cells. Proc Natl Acad Sci U S A . 1989;;86:4287-4290.
18 +
Cheng-Mayer C, Rutka JT, Rosenblum ML, McHugh T, Stites DP, Levy JA.  Human immunodeficiency virus can productively infect cultured human glial cells. Proc Natl Acad Sci U S A . 1987;; 84:3526-3530.
19 +
McClure MO, Marsh M, Weiss RA.  Human immunodeficiency virus infection of CD4-bearing cells occurs by a pH-independent mechanism. EMBO J . 1988;;7:513-518.
20 +
Stein BS, Gowda SD, Lifson JD, Penhallow RC, Bensch KG, Engelman EG.  pH-independent HIV entry into CD4-positive cells via virus envelope fusion to the plasma membrane. Cell . 1987;;49:659-668.
21 +
Hu WS, Temin HM.  Retroviral recombination and reverse transcription. Science . 1990;;250:1227-1233.
22 +
Panganiban AT, Fiore D.  Ordered interstrand and intrastrand DNA transfer during reverse transcription. Science . 1988;;241:1064-1069.
23 +
Panganiban AT.  Retroviral reverse transcription and DNA integration. Semin Virol . 1990;;1: 187-194.
24 +
Cullen BR, Greene WC.  Regulatory pathways governing HIV-1 replication. Cell . 1989;;58:423-426.
25 +
Aldovini A, Young R.  Mutations of RNA and protein sequences involved in human immunodeficiency virus type 1 packaging result in production of noninfectious virus. J Virol . 1990;;64:1920-1926.
26 +
Clavel F, Orenstein JM.  A mutant of human immunodeficiency virus with reduced RNA packaging and abnormal particle morphology. J Virol . 1990;;64:5230-5234.
27 +
Lever A, Gottlinger H, Haseltine W, Sodroski J.  Identification of a sequence required for efficient packaging of human immunodeficiency virus type 1 RNA into virions. J Virol . 1989;;63:4085-4087.
28 +
Freed EO, Myers DJ, Risser R.  Mutational analysis of the cleavage sequence of the human immunodeficiency virus type 1 envelope glycoprotein precursor gp160. J Virol . 1989;;63:4670-4675.
29 +
Miller AD.  Retrovirus packaging cells. Hum Gene Ther . 1990;;1:5-14.
30 +
Rosenberg SA.  Gene therapy for cancer. JAMA . 1992;;268:2416-2419.
31 +
Thompson L.  At age 2 gene therapy enters a growth phase. Science . 1992;;258:744-746.
32 +
Rosenberg SA, Aebersold P, Cornetta K, et al.  Gene transfer into humans: immunotherapy of patients with advanced melanoma using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med . 1990;;323:570-578.
33 +
Freed EO, Delwart EL, Buchschacher GL Jr, Panganiban AT.  A mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity. Proc Natl Acad Sci USA . 1992;;89:70-74.
34 +
Helseth E, Kowalski M, Gabuzda D, Olshevsky U, Haseltine W, Sodroski J.  Rapid complementation assays measuring replicative potential of human immunodeficiency virus type 1 envelope glycoprotein mutants. J Virol . 1990;;64:2416-2420.
35 +
Page KA, Landau NR, Littman DR.  Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity. J Virol . 1990;; 64:5270-5276.
36 +
Poznansky M, Leveer A, Bergeron L, Haseltine W, Sodroski J.  Gene transfer into human lymphocytes by a defective human immunodeficiency virus type 1 vector. J Virol . 1991;;65:532-536.
37 +
Buchschacher GL Jr, Panganiban AT.  Human immunodeficiency virus vectors for inducible expression of foreign genes. J Virol . 1992;;66:2731-2739.
38 +
Harrison GS, Maxwell F, Long CJ, Rosen CA, Glode LM, Maxwell IH.  Activation of a diphtheria toxin A gene by expression of human immunodeficiency virus-1 tat and rev proteins in transfected cells. Hum Gene Ther . 1991;;2:53-60.
39 +
Rossi JJ, Elkins D, Zaia JA, Sullivan S.  Ribozymes as anti-HIV therapeutic agents: principles, applications, and problems. AIDS Res Hum Retroviruses . 1992;;8:183-189.
40 +
Warner JF, Anderson C, Laube L, et al.  Induction of HIV-specific CTL and antibody responses in mice using retroviral vector-transduced cells. AIDS Res Hum Retroviruses . 1991;;7:645-655.
41 +
Riddell SR, Greenberg PD, Overell RW, et al.  Phase I study of cellular adoptive immunotherapy using genetically modified CD8+ HIV-specific T cells for HIV seropositive patients undergoing allogeneic bone marrow transplant. Hum Gene Ther . 1992;;3:319-338.
42 +
Venkatesh LK, Arens MQ, Subramanian T, Chinnadurai G.  Selective induction of toxicity to human cells expressing human immunodeficiency virus type 1 Tat by a conditionally cytotoxic adenovirus vector. Proc Natl Acad Sci U S A . 1990;; 87:8746-8750.
43 +
Caruso M, Klatzman D.  Selective killing of CD4+ cells harboring a human immunodeficiency virus— inducible suicide gene prevents viral spread in an infected cell population. Proc Natl Acad Sci U S A . 1992;;89:182-186.
44 +
Yamaizumi ME, Mekada E, Uchida T, Okada Y.  One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell. Cell . 1978;;15: 245-250.
45 +
Harrison GS, Long CJ, Maxwell F, Glode LM, Maxwell IH.  Inhibition of HIV production in cells containing an integrated HIV-regulated diphtheria toxin A chain gene. AIDS Res Hum Retroviruses . 1992;;8:39-45.
46 +
Harrison GS, Long CJ, Curiel TJ, Maxwell F, Maxwell IH.  Inhibition of human immunodeficiency virus-1 production resulting from transduction with a retrovirus containing an HIV-regulated diphtheria toxin A chain gene. Hum Gene Ther . 1992;; 3:461-469.
47 +
Sullenger BA, Gallardo HF, Ungers GE, Gilboa E.  Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Cell . 1990;;63:601-608.
48 +
Sullenger BA, Gallardo HF, Ungers GE, Gilboa E.  Analysis of trans-acting response decoy RNA-mediated inhibition of human immunodeficiency virus type 1 transactivation. J Virol . 1991;;65:6811-6816.
49 +
Lisziewicz J, Rappaport J, Dhar R.  Tat-regulated production of multimerized TAR RNA inhibits HIV-1 gene expression. New Biologist . 1991;;3: 82-89.
50 +
Lee TC, Sullinger BA, Gallardo HF, Ungers GE, Gilboa E.  Overexpression of RRE-derived sequences inhibits HIV-1 replication in CEM cells. New Biologist . 1992;;4:66-74.
51 +
Joshi S, van Brunschot A, Asad S, van der Elst I, Read SE, Berstein A.  Inhibition of human immunodeficiency virus type 1 multiplication by antisense and sense RNA expression. J Virol . 1991;; 65:5524-5530.
52 +
Sczakiel G, Oppenlander M, Rittner K, Pawlita M.  Tat- and Rev-directed antisense RNA expression inhibits and abolishes replication of human immunodeficiency virus type 1: a temporal analysis. J Virol . 1992;;66:5576-5581.
53 +
Rhodes A, James W.  Inhibition of human immunodeficiency virus replication in cell culture by endogenously synthesized antisense RNA. J Gen Virol . 1990;;71:1965-1974.
54 +
Chatterjee S, Johnson PR, Wong KK Jr.  Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus antisense vector. Science . 1992;;258:1485-1488.
55 +
Sarver N, Cantin EM, Chang PS, et al.  Ribozymes as potential anti-HIV therapeutic agents. Science . 1990;;247:1222-1225.
56 +
Dropulic B, Lin NH, Martin MA, Jeang K.  Functional characterization of a U5 ribozyme: intracellular suppression of human immunodeficiency virus type 1 expression. J Virol . 1992;;66:1432-1441.
57 +
Weerasinghe M, Liem SE, Sabah S, Read SE, Joshi S.  Resistance to human immunodeficiency virus type 1 (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme. J Virol . 1991;;65:5531-5534.
58 +
Ojwang JO, Hampel A, Looney DJ, Wong-Staal F, Rappaport J.  Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. Proc Natl Acad Sci U S A . 1992;;89:10802-10806.
59 +
Sioud M, Drlica K.  Prevention of human immunodeficiency virus type 1 integrase expression in Escherichia coli by a ribozyme. Proc Natl Acad Sci U S A . 1991;;88:7303-7307.
60 +
Feinberg MB, Trono D.  Intracellular immunization: Trans-dominant mutants of HIV gene products as tools for the study and interruption of viral replication. AIDS Res Hum Retroviruses . 1992;;8: 1013-1022.
61 +
Green M, Ishino M, Loewenstein PM.  Mutational analysis of HIV-1 Tat minimal domain peptides: identification of trans-dominant mutants that suppress HIV-LTR—driven gene expression. Cell . 1989;;58:215-223.
62 +
Tiley LS, Brown PH, Cullen BR.  Does the human immunodeficiency virus Tat trans-activator contain a discrete activation domain? Virology . 1990;; 178:560-567.
63 +
Pearson L, Garcia J, Wu F, Modesti N, Nelson J, Gaynor R.  A transdominant tat mutant that inhibits Tat-induced gene expression from the human immunodeficiency virus long terminal repeat. Proc Natl Acad Sci U S A . 1990;;87:5079-5083.
64 +
Malim MH, Bohnlein S, Hauber J, Cullen BR.  Functional dissection of the HIV-1 Rev trans-activator—derivation of a trans-dominant repressor of Rev function. Cell . 1989;;58:205-214.
65 +
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To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
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Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
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