HIV-1 Gag mutants can dominantly interfere with the replication of the wild-type virus.

The products of the human immunodeficiency virus (HIV) gag gene exist in a highly multimerized state in the mature virion. For that reason, they may represent a particularly suitable target for the generation of dominant negative mutants. A number of HIV site-directed Gag mutants did show interference with the production of infectious viral particles from cells in which they were cotransfected with a wild-type proviral DNA.

Stable expression of the tax gene of type I human T-cell leukemia virus in human T cells activates specific cellular genes involved in growth.

Stable expression of the 40-kDa transactivator protein (Tax) from the type I human T-cell leukemia virus (HTLV-I) in Jurkat T cells leads to the activation and sustained expression of certain cellular genes that are transiently induced during normal T-cell growth. Cellular genes induced by Tax include those encoding the alpha subunit of the high-affinity interleukin 2 receptor (Tac), interleukin 2, and granulocyte/macrophage colony-stimulating factor. Tax induction of the interleukin 2 gene is synergistically amplified by mitogens that augment cytoplasmic levels of calcium.

Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus.

The envelope protein of human immunodeficiency virus (HIV) is synthesized as a polyprotein (gp160) and cleaved intracellularly to a gp120-gp41 heterodimer. In this study, the tryptic-like endoproteolytic cleavage site was removed by site-directed mutagenesis and replaced with a chymotryptic-like site. The resultant mutant, RIP7/mut10, was found to be indistinguishable from wild-type HIV when analyzed at the level of proviral replication, RNA processing, protein expression, and viral assembly.

Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans-activator (tat) gene product of human T-cell leukemia virus, type I.

Cotransfection of cDNA encoding the trans-activator gene product of human T-cell leukemia virus, type I (HTLV-I) (tat-I), which acts in trans to augment viral gene expression, has revealed strong regulatory effects of this viral protein on the inducible cellular promoters governing human interleukin 2 (IL-2) and IL-2 receptor (Tac) gene expression. The tat-I protein stimulates a 3- to 6-fold increase in IL-2 receptor (Tac) promoter activity in transfected Jurkat T cells, but not in the natural killer-like YT cell line, as measured by changes in the expression of the chloramphenicol acetyltransferase (CAT; EC 2.3.

Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I.

We have characterized regulatory regions of the human IL-2 receptor alpha chain (IL2R alpha) promoter. 5' deletion constructs extending to -327 directed CAT expression in HTLV-I-infected T cells, which express IL2R alpha constitutively, and in Jurkat cells, which express IL2R alpha only after induction. Deletions to -267 and -265 were active only in HTLV-I-transformed T cells, but their activity in Jurkat cells was restored by cotransfection of a construct expressing the HTLV-I transactivator protein (tat-I).

Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein.

Formation of syncytia, with progression to cell death, is a characteristic feature of in vitro cultures of susceptible cells infected with human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). Viral antigen-positive multinucleated giant cells have also been observed in histological sections from infected individuals. In vitro, formation of these multinucleated giant cells occurs through cell fusion which is dependent on cell-surface expression of the differentiation antigen CD4.

HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA.

The African green monkey nonlymphoid cell line cos-1 produces infectious HTLV-III virus following transfection with biologically active molecular clones of HTLV-III. Transfected cos-1 cells produce large amounts of viral RNA and protein. We have used this rapid transfection system to study the regulatory functions and synthetic capacity of the HTLV-III genome, as well as mutants derived from it.

Association of tumor differentiation with caffeine and coffee intake in women with breast cancer.

Caffeine, which has been linked to benign breast disease, has an antineoplastic effect in experimental animals, whereas in tissue cultures it inhibits mitoses and induces cell differentiation. We examined caffeine and coffee intake in 101 women with breast cancer to determine whether either or both influence cell differentiation in tumors as well. Nutrient analysis was performed by the Nutrition Coding Center of the University of Minnesota with the Nutrition Data system from the National Heart, Lung, and Blood Institute.

Synthesis of the complete trans-activation gene product of human T-lymphotropic virus type III in Escherichia coli: demonstration of immunogenicity in vivo and expression in vitro.

Human T-lymphotropic virus type III (HTLV-III) contains a gene (tat-III) the product of which activates the expression of viral genes in trans. We have expressed in Escherichia coli the complete tat-III-encoded protein as well as a truncated form that lacks three amino acids from the amino terminus. These proteins are recognized by sera of many, but not all, infected individuals including patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex, as well as asymptomatic seropositive persons.

Transformation of T-lymphoid cells by Abelson murine leukemia virus.

Abelson leukemia virus (A-MuLV) is an oncogenic murine retrovirus whose genome contains sequences homologous to those of a normal cellular gene, c-abl. It has been demonstrated to cause rapid transformation of several cell types, including pre-B lymphocytes, macrophages, and fibroblasts. More recently, A-MuLV has been reported to induce thymic tumors in a mouse strain (C57BL/Ka) previously thought to be resistant to disease induction.

Simultaneous panic and depressive disorders: clinical and sleep EEG correlates.

Panic and depressive symptoms occur simultaneously in many depressed patients. To study the frequency of this association and to determine whether patients with simultaneous panic and major depression differed from those with only major depressive disorder (MDD) in clinical features and in sleep electroencephalographic (EEG) variables, we evaluated a total sample of 336 patients with MDD. Fifty-eight (17%) had both panic and MDD; 50 had complete data and were matched for age and severity of illness with other patients having only MDD.

The trans-activator gene of HTLV-III is essential for virus replication.

Studies of the genomic structure of human T-lymphotropic virus type III (HTLV-III) and related viruses, implicated as the causal agent of acquired immune deficiency syndrome (AIDS), have identified a sixth open reading frame in addition to the five previously known within the genome (gag, pol, sor, env and 3'orf). This gene, called tat-III, lies between the sor and env genes and is able to mediate activation, in a trans configuration, of the genes linked to HTLV-III long terminal repeat (LTR) sequences. We now present evidence that the product of tat-III is an absolute requirement for virus expression.

Facial electromyography in depression. Subgroup differences.

To study whether facial electromyographic (EMG) activity during affective imagery differed between normal subjects and depressive subtypes, we evaluated EMG responses in 29 normal controls, 37 endogenously depressed patients, and 26 nonendogenously depressed patients. Different imagery states produced more distinctive EMG patterns in normal controls than in depressed patients. Patients with endogenous depression had EMG levels that differentiated them from normal subjects and had significantly greater absolute values than the nonendogenous group in corrugator happy and corrugator sad imagery trials.

Coexistence of primary Crohn's disease and carcinoid tumor isolated to the appendix. A case report.

A patient is described in whom isolated Crohn's disease of the appendix was present simultaneously with isolated carcinoid tumor of the appendix. Appendectomy was the primary therapy and no recurrence of either disease has been discovered after four years of follow-up. We believe this to be the first case of its type to be reported.

Transactivation induced by human T-lymphotropic virus type III (HTLV III) maps to a viral sequence encoding 58 amino acids and lacks tissue specificity.

The acquired immune deficiency syndrome (AIDS) retrovirus, HTLV-III/LAV, encodes a transacting factor which directly or indirectly stimulates the expression of genes linked to its LTR. To further dissect this phenomenon, we have cotransfected a biologically active molecular clone of HTLV-III and a recombinant plasmid containing an indicator gene, the bacterial gene for chloramphenicol acetyltransferase (CAT), under the control of the HTLV-III LTR. Amplified CAT activity was detected in both lymphoid cells and fibroblasts from a number of species in the presence of the proviral DNA.

Molecular analysis of a deletion mutant provirus of type I human T-cell lymphotropic virus: evidence for a doubly spliced x-lor mRNA.

The genome of the human T-cell leukemia/lymphotropic virus type I (HTLV-I) contains a functional gene denominated x-lor that may be important in HTLV-I transformation of human T cells. To study the role of x-lor and other HTLV-I genes in cellular transformation, we obtained a transformed nonproducer human T-cell line containing a single defective HTLV-I provirus (HTLV-I 55/PL). This 7-kilobase provirus had undergone a deletion involving the entire envelope gene and the nonconserved region.

Multiple sclerosis and human T-cell lymphotropic retroviruses.

A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

Plasma cortisol determination for the dexamethasone suppression test. Comparison of competitive protein-binding and commercial radioimmunoassay methods.

Quality control serum samples and postdexamethasone plasma pools were used to compare 16 commercial cortisol radioimmunoassay kits with the competitive protein-binding assay for plasma glucocorticoids that we used to standardize the dexamethasone suppression test (DST). Thirteen radioimmunoassays gave higher criterion values for the DST than those established using the competitive protein-binding assay. The range of radioimmunoassay criterion values was 4.

Patterns of thymocyte differentiation markers on virus and radiation induced lymphomas of C57BL/Ka mice.

To better understand the biology of tumorigenesis in virus and radiation lymphomas of C57Bl/Ka mice, we have examined the cell surface phenotypes of a large series of primary tumors induced by both agents. Data derived using flow cytometry and recently available monoclonal antibodies to thymocyte differentiation antigens supports three major conclusions. First, tumor cell populations are unimodal for staining with most antibodies and are probably of clonal origin.