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Biomedical subjects

A B Jaffe

Publications and source records attributed to A B Jaffe.

14 recordsLinked to original sources
PubMed2001

Structure-specific abnormalities associated with mutations in a DNA replication accessory factor in Drosophila.

We have phenotypically and molecularly analyzed the cutlet locus in Drosophila. Homozygous cutlet flies exhibit abnormal development of a subset of adult tissues, including the eye, wing, and ovary. We show that abnormal development of these tissues is due to a defect in normal cell growth. Surprisingly, cell growth is affected in all developing precursor tissues in cutlet mutant animals, including those that give rise to phenotypically wild-type adult structures. The cutlet gene encodes a Drosophila homologue of yeast CHL12 and has similarity to mammalian replication factor C. In addition, cutlet genetically interacts with multiple subunits of Drosophila replication factor C. Our results suggest that the cutlet gene product acts as an accessory factor for DNA replication and has different requirements for the formation of various adult structures during Drosophila development.

Amino Acid Sequence↗
PubMed1998

A novel membrane protein is a mouse mammary tumor virus receptor.

Mouse mammary tumor virus (MMTV) infects a number of different cell types, including mammary gland and lymphoid cells, in vivo. To identify the cellular receptor for this virus, a mouse cDNA expression library was transfected into Cos-7 monkey kidney cells, and those transfected cells able to bind virus were selected by using antibody against the virus's cell surface envelope protein, gp52. One clone isolated from a library prepared from newborn thymus RNA, called MTVR, was able to confer virus binding to both monkey and human cells; this binding was blocked by anti-MTVR antibody. Moreover, transfection of MTVR into CV1 cells rendered them susceptible to infection by a murine leukemia virus-based retrovirus vector pseudotyped with the MMTV envelope protein. An epitope-tagged MTVR cofractionated with cellular membranes. Coimmunoprecipitation of the MMTV envelope protein and a MTVR-rabbit Fc fusion protein showed that these two proteins bound to each other. The MTVR sequence clone is unique, shows no homology to known membrane proteins, and is transcribed in many tissues.

Amino Acid Sequence↗
PubMed1997

Determinants of pain expression in hospitalized burn patients.

This study examines the relationship between extent of injury, degree and type of psychological distress and self-report of pain in burn survivors. One hundred eighty burn patients were interviewed within 2 weeks of their burn trauma. Using a visual analogue scale to assess subjective pain and pain relief, and self-report measures of post-traumatic stress symptoms and general psychological distress, we assessed the relationship between PTSD symptoms, general distress and pain. Subjective pain was unrelated to sex, ethnicity, or total body surface area burned. The most important correlate of subjective pain was general psychological distress. Intrusive PTSD symptoms had no independent power to predict the variance in pain scores. However, among women, more severe avoidant symptoms were associated with greater subjective pain.

Adaptation, Psychological↗
PubMed1997

Transcriptional activation and repression by RORalpha, an orphan nuclear receptor required for cerebellar development.

Mutation of the orphan nuclear receptor RORalpha results in a severe impairment of cerebellar development by unknown mechanisms. We have found that RORalpha activates transcription from only a subset of sites to which it binds strongly as a monomer. RORalpha also selectively binds as a homodimer to a direct repeat of this monomer site with a 2-bp spacing between the AGGTCA sequences (Rev-DR2 site) and is a much more potent transcriptional activator on this site than on monomer sites or other direct repeats. To better understand the transcriptional regulatory functions of RORalpha, we fused its C terminus to a heterologous DNA-binding domain. Mutational analysis revealed that RORalpha contains both transcriptional activation and transcriptional repression domains, with the repression domain being more active in some cell types. The abilities of RORalpha polypeptides to repress transcription correlate with their abilities to interact with the nuclear receptor corepressors N-CoR and SMRT in vitro. However, the AF2 region of RORalpha inhibits corepressor interaction on DNA, consistent with the lack of repression by the full-length receptor. Thus, transcriptional regulation by RORalpha is complex and likely to be regulated in a cell type- and target gene-specific manner.

Animals↗
PubMed1996

Trends and patterns in research and development expenditures in the United States.

This paper is a review of recent trends in United States expenditures on research and development (R&D). Real expenditures by both the government and the private sector increased rapidly between the mid-1970s and the mid-1980s, and have since leveled off. This is true of both overall expenditures and expenditures on basic research, as well as funding of academic research. Preliminary estimates indicate that about $170 billion was spent on R&D in the United States in 1995, with approximately 60% of that funding coming from the private sector and about 35% from the federal government. In comparison to other countries, we have historically spent more on R&D relative to our economy than other advanced economies, but this advantage appears to be disappearing. If defense-related R&D is excluded, our expenditures relative to the size of the economy are considerably smaller than those of other similar economies.

Costs and Cost Analysis↗
PubMed1996

Flows of knowledge from universities and federal laboratories: modeling the flow of patent citations over time and across institutional and geographic boundaries.

The extent to which new technological knowledge flows across institutional and national boundaries is a question of great importance for public policy and the modeling of economic growth. In this paper we develop a model of the process generating subsequent citations to patents as a lens for viewing knowledge diffusion. We find that the probability of patent citation over time after a patent is granted fits well to a double-exponential function that can be interpreted as the mixture of diffusion and obsolescense functions. The results indicate that diffusion is geographically localized. Controlling for other factors, within-country citations are more numerous and come more quickly than those that cross country boundaries.

Canada↗
PubMed1996

Human immunodeficiency virus type 1 Vif does not influence expression or virion incorporation of gag-, pol-, and env-encoded proteins.

The Vif protein of human immunodeficiency virus type 1 is required for productive replication in peripheral blood lymphocytes and a limited number of immortalized T-lymphoid lines (nonpermissive cells). In contrast, Vif is fully dispensable for virus replication in other T-cell lines (permissive cells). Because the infection phenotype of released virions is determined by producer cells and by the presence of Vif in those cells, we have analyzed the protein contents of purified viral particles in an attempt to define compositional differences that could explain the infection phenotype. Surprisingly, we were unable to discern any Vif- or cell-type-dependent quantitative or qualitative difference in the Gag, Pol, and Env proteins of virions or virus-producing cells that correlates with virus infectivity. We were, however, able to demonstrate that Vif itself is present in virions and, using semiquantitative Western blotting (immunoblotting), that there is an average of 30 to 80 molecules of Vif incorporated into each virion. Importantly, parallel analyses of total lysates of the producer cells revealed that the cell-associated expression levels of Vif are close to those of the Gag proteins. Given the dramatically higher abundance of Vif in cells than in virions, we speculate that Vif exerts its principal activity during the processes of virus assembly and budding and that this function could be of a structural-conformational nature.

Gene Deletion↗
PubMed1995

Chromosomal location and structural organization of the human deoxycytidylate deaminase gene.

Deoxycytidylate deaminase is an allosteric enzyme whose impairment can lead to deoxynucleotide imbalances that affect the fidelity of DNA synthesis. A DNA fragment encompassing the gene for deoxycytidylate deaminase has been isolated from a human lung fibroblast genomic library and sequenced in both directions through 26,764 base pairs. The previously isolated cDNA, which was used to establish the amino acid sequence for this enzyme (Weiner, K.X.B., Weiner, R.S., Maley, F., and Maley, G.F. (1993) J. Biol. Chem. 268, 12983-12989) was instrumental in isolating this gene. The gene consists of five exons of about 100 base pairs each, separated by four introns. The most striking feature of the genomic structure is that the second and third exons are separated by an intron of about 20 kilobases. The chromosomal location of the deaminase gene was determined by fluorescence in situ hybridization as 4q35, which is the extreme end of this chromosome. The position of this gene on chromosome 4, in addition to the role of its product in limiting potentially detrimental mutations, suggests that the normal operation of both the gene and its product is important to the well being of the organism.

Base Sequence↗
PubMed1995

Mouse mammary tumor viruses with functional superantigen genes are selected during in vivo infection.

Mouse mammary tumor virus (MMTV) encodes a superantigen that is important for viral infectivity in vivo. To determine whether superantigen function was required for infection by milk-borne MMTV, we created HYB PRO/Cla transgenic mice. These mice produced a full-length, packaged viral RNA with a frameshift mutation that caused premature termination of the superantigen protein. Young HYB PRO/Cla mice showed no deletion of their cognate V beta 14+ T cells, although they shed virus in their milk. The nontransgenic offspring of the HYB PRO/Cla mice were infected with this virus, since transgene-specific viral transcripts were detected in their mammary glands. Surprisingly, these offspring demonstrated the progressive deletion of V beta 14+ T cells characteristic of exogenous MMTV (C3H) infection. Sequence analysis demonstrated that these newly acquired viruses had reconstituted superantigen open reading frames resulting from recombination between the HYB PRO/Cla and endogenous Mtv-1 proviral RNAs. Thus, there is selection during the infection process for MMTVs with functional superantigen genes.

Amino Acid Sequence↗
PubMed1994

Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein.

We have investigated the possible effect of estrogen on the metabolism of the Alzheimer amyloid precursor protein (APP). Using a cell line that contains high levels of estrogen receptors, we have found that treatment with physiological concentrations of 17 beta-estradiol is associated with accumulation in the conditioned medium of an amino-terminal cleavage product of APP (soluble APP or protease nexin-2), indicative of non-amyloidogenic processing. There were no obvious changes in the levels of intracellular immature or mature APP holoproteins, suggesting that estrogen may increase the secretory metabolism of APP.

Amyloid beta-Protein Precursor↗
PubMed1994

Coexpression of exogenous and endogenous mouse mammary tumor virus RNA in vivo results in viral recombination and broadens the virus host range.

Mouse mammary tumor virus is a replication-competent B-type murine retrovirus responsible for mammary gland tumorigenesis in some strains of laboratory mice. Mouse mammary tumor virus is transmitted horizontally through the milk (exogenous or milk-borne virus) to susceptible offspring or vertically through the germ line (endogenous provirus). Exogenously acquired and some endogenous mouse mammary tumor viruses are expressed at high levels in lactating mammary glands. We show here that there is packaging of the endogenous Mtv-1 virus, which is expressed at high levels in the lactating mammary glands of C3H/HeN mice, by the virions of exogenous C3H mouse mammary tumor virus [MMTV(C3H)]. The mammary tumors induced in C3H/HeN mice infected with exogenous MMTV (C3H) virus contained integrated copies of recombinant virus containing a region of the env gene from an endogenous virus. This finding indicates that there was copackaging of the Mtv-1 and MMTV(C3H) RNAs in the same virions. Moreover, because Mtv-1 encodes a superantigen protein with a V beta specificity different from that encoded by the exogenous virus, the packaging of Mtv-1 results in an infectious virus with a broader host range than MMTV(C3H).

Animals↗
PubMed1989

Rats self-administer sufentanil in aerosol form.

An ultrasonic nebulizer was used to create a drug vapor to develop an animal model for the self-administration of inhaled nonvolatile psychoactive drugs. An aerosol mist of a sufentanil citrate solution (10, 25, 50, or 75 micrograms/ml) was delivered to rats in response to lever presses on an FR 5 schedule of reinforcement. The speed of acquisition of the operant response and the selectivity of the drug effect were examined. Rats given access to sufentanil vapor (50 or 75 micrograms/ml) in 13-15 h overnight training sessions reached an average of one reinforcement per hour on an FR 5 schedule of reinforcement significantly sooner than did rats given access to water vapor. Responding maintained by sufentanil during 2-h daily testing sessions was dose dependent at 25, 50, and 75 micrograms/ml. Substituting water vapor for each of the four sufentanil concentrations significantly reduced responding within 5-20 sessions. Naloxone (1 mg/kg, IP) decreased responding for sufentanil to the level attained under water vapor. Presentation of drugs in aerosol form thus provides reasonable means of demonstrating in animals the reinforcing properties of non-volatile drugs by the pulmonary or intranasal route.

Aerosols↗