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Biomedical subjects

N Hopkins

Publications and source records attributed to N Hopkins.

At least 55 records · Page 3Linked to original sources
PubMed1994

HIV-1 infection at two public psychiatric hospitals in New York City.

Seroprevalence for HIV-1 was anonymously evaluated between November 1989 and July 1991 among severely mentally ill patients at two public psychiatric hospitals in New York City. The study population consisted of new admissions and long-stay patients aged 18-59. Of 1116 eligible patients, usable samples were obtained from routine blood drawings on 971 (87%). Seroprevalence was comparable among men (5.2%) and women (5.3%). Age did not predict seropositivity. Men with a recorded history of homosexual behaviour or injection drug use were, respectively, 1.8 and 2.0 times more likely to be seropositive than men without these histories. Women with a recorded history of injection drug use were 4.0 times more likely to be seropositive than women without such a history. Ethnicity was not predictive for men, but Black women were 2.4 times more likely to be HIV-1 positive than non-Black women. Severely mentally ill inpatients had a substantial rate of HIV-1 seropositivity, indicating a need for additional testing, education and counselling efforts for this population.

Adolescent↗
PubMed1993

Two factors that bind to highly conserved sequences in mammalian type C retroviral enhancers.

The transcriptional enhancers of the Moloney and Friend murine leukemia viruses (MLV) are important determinants of viral pathogenicity. We used electrophoretic mobility shift and methylation interference assays to study nuclear factors which bind to a region of these enhancers whose sequence is identical between Moloney and Friend viruses and particularly highly conserved among 35 mammalian type C retroviruses whose enhancer sequences have been aligned (E. Golemis, N. A. Speck, and N. Hopkins, J. Virol. 64:534-542, 1990). Previous studies identified sites for the leukemia virus factor b (LVb) and core proteins in this region (N. A. Speck and D. Baltimore, Mol. Cell. Biol. 7:1101-1110, 1987) as well as a site, overlapping those for LVb and core, for a third factor (N. R. Manley, M. A. O'Connell, P. A. Sharp, and N. Hopkins, J. Virol. 63:4210-4223, 1989). Surprisingly, the latter factor appeared to also bind two sites identified in the Friend MLV enhancer, Friend virus factor a and b1 (FVa and FVb1) sites, although the sequence basis for the ability of the protein to bind these diverse sites was not apparent. Here we describe the further characterization of this binding activity, termed MCREF-1 (for mammalian type C retrovirus enhancer factor 1), and the identification of a consensus sequence for its binding, GGN8GG. We also identify a factor, abundant in mouse T-cell lines and designated LVt, which binds to two sites in the Moloney MLV enhancer, overlapping the previously identified LVb and LVc binding sites. These sites contain the consensus binding site for the Ets family of proteins. We speculate on how distinct arrays of these factors may influence the disease-inducing phenotype.

Animals↗
PubMed1993

The NF-kappa B binding site is necessary for efficient replication of simian immunodeficiency virus of macaques in primary macrophages but not in T cells in vitro.

We demonstrate here that the nuclear factor-kappa B (NF-kappa B) binding site in the simian immunodeficiency virus (SIVmac) long terminal repeat is essential for efficient virus replication in primary alveolar macrophages but dispensable for efficient replication in primary T cells. Mutation of the NF-kappa B site does not seriously impair replication of a T-cell-tropic SIVmac239 or a macrophagetropic SIVmacEm* in peripheral blood lymphocytes or established CD4+ cell lines; however, mutation of the NF-kappa B site prevents efficient SIVmacEm* replication in primary alveolar macrophages. These data suggest that efficient replication in primary macrophages requires both envelope and long terminal repeat determinants.

Animals↗
PubMed1992

Production of germ-line chimeras in zebrafish by cell transplants from genetically pigmented to albino embryos.

To determine whether embryonic cells transplanted from one zebrafish embryo to another can contribute to the germ line of the recipient, and to determine whether pigmentation can be used as a dominant visible marker to monitor cell transplants, we introduced cells from genetically pigmented (donor) embryos to albino recipients at midblastula stage. By 48 hr many of the resulting chimeras expressed dark pigment in their eyes and bodies, characteristics of donor but not albino embryos. By 4-6 weeks of age pigmentation was observed on the body of 23 of 70 chimeras. In contrast to fully pigmented wild-type fish, pigmentation in chimeras appeared within transverse bands running from dorsal to ventral. Pigmentation patterns differed from one fish to another and in almost every case were different on each side of a single fish. At 2-3 months of age chimeras were mated to albino fish to determine whether pigmented donor cells had contributed to the germ line. Of 28 chimeric fish that have yielded at least 50 offspring each, 5 have given rise to pigmented progeny at frequencies of 1-40%. The donor cells for some chimeras were derived from embryos that, in addition to being pigmented, were transgenic for a lacZ plasmid. Pigmented offspring of some germ-line chimeras inherited the transgene, confirming that they descended from transplanted donor cells. Our ability to make germ-line chimeras suggests that it is possible to introduce genetically engineered cells into zebrafish embryos and to identify the offspring of these cells by pigmentation at 2 days of age.

Albinism↗
PubMed1992

Police-schools liaison and young people's image of the police: an intervention evaluation.

This paper evaluates the impact of Police-Schools Liaison on young people's views and attitudes about the police and offending. It reports the first, large-scale, independent evaluation of this social intervention. The evaluation (based on 1245 secondary-school pupils) compares views of the police in schools with (target) and without (control) a full-time Schools Liaison Officer (SLO). Although attitudes to the police are marginally positive, they become less so over one year. There is no evidence that Schools Liaison input into the target schools slows or halts this decline, or that it affects perceptions of the seriousness of offences, and the likelihood of identification associated with crime. This weak impact is, at least in part, attributable to the low reported rates of direct contact, and the judged atypicality of the SLO. Target-school pupils judged their SLO positively, but as distinct from the 'police in general'. Their view of the SLO had a direct impact on their liking of the police in general, but there was no effect for contact. We conclude that Police-Schools Liaison has only limited positive effects, as predicted from critiques of the traditional 'contact hypothesis'.

Adolescent↗
PubMed1992

Nuclear factors that bind two regions important to transcriptional activity of the simian immunodeficiency virus long terminal repeat.

Previous studies identified two regions in the U3 region of a molecular clone of simian immunodeficiency virus, SIVmac142, that are important to transcriptional activity under conditions of induction as well as basal-level expression (B. Renjifo, N. A. Speck, S. Winandy, N. Hopkins, and Y. Li, J. Virol. 64:3130-3134, 1990). One region includes the NF-kappa B binding site, while the other lies just 5' of this site between nucleotides -162 and -114 (the -162 to -114 region). The fact that the NF-kappa B site mutation attenuated transcriptional activity in uninduced T cells and fibroblasts where activated NF-kappa B would not be present suggested that a factor(s) other than NF-kappa B could be acting through this site. In this study, we have identified a factor which binds to a cis element overlapping the NF-kappa B site. This factor, which we call simian factor 3 (SF3), would play a role in regulation under conditions of basal level expression, whereas under conditions of induction, NF-kappa B would act via this region. SF3 may also bind to an element in the -162 to -114 region. In addition, we have identified two other factors that bind the -162 to -114 region. One, which we designated SF1, is a ubiquitous basal factor, and the other, SF2, is a T-cell-predominant phorbol myristate acetate-inducible factor. Through identification of nuclear factors that interact with the U3 region of the SIVmac142 long terminal repeat, we can gain insight into how this virus is transcriptionally regulated under conditions of basal-level expression as well as conditions of T-cell activation.

Animals↗
PubMed1991

High-frequency germ-line transmission of plasmid DNA sequences injected into fertilized zebrafish eggs.

With the goal of developing techniques for DNA insertional mutagenesis in zebrafish, we established procedures for rapidly obtaining and injecting large numbers of fertilized eggs. Using either of two plasmid constructs, we injected uncut DNA into fertilized eggs at the one- or two-cell stage. Fish hatched from injected eggs were raised to sexual maturity, and the frequency of transgenic founder fish was determined by pair-mating the fish and testing DNA extracted from pools of their 16-hr-old offspring by the polymerase chain reaction (PCR) and then Southern analysis. Eggs injected with one of two different plasmids yielded no transgenic fish, but 7-25% (19 of 115 overall) of the eggs injected with the other plasmid transmitted the injected sequences to their offspring (F1). Of seven lines studied further, all were able to pass the foreign DNA sequences to the next (F2) generation. Inheritance in the F2 generation was Mendelian in the five lines tested. PCR and Southern analysis indicated that the plasmid sequences were present in multiple copies, probably tandemly arranged. Two founder fish carried more than one independent integration of the plasmid sequences. The line studied in more detail was a mosaic carrying two independently segregating copies of the transgene in one germ cell and a third copy in another germ-line precursor cell. The ability to obtain and inject large numbers of zebrafish eggs combined with a high frequency of germ-line integration may be steps toward the goal of being able to perform insertional mutagenesis with this organism.

Animals↗
PubMed1991

Isolation and characterization of irradiation fusion hybrids from mouse chromosome 1 for mapping Rmc-1, a gene encoding a cellular receptor for MCF class murine retroviruses.

An irradiation-reduced somatic cell hybrid mapping panel was constructed of BALB/c mouse Chromosome 1. Nineteen hybrids were selected from a pool of 292 clones to generate a fine structure physical map of the distal 40 cM of the chromosome. The hybrids contain mouse DNA fragments only from Chromosome 1, ranging from approximately 5 cM to approximately 20 cM. Utilizing a viral infectibility assay, a cellular receptor gene, Rmc-1, for the MCF class of murine retroviruses was found to be linked to Lamb2, in the region between the Lamb2 and Bxv-1 loci. In addition, analysis of the hybrid mapping panel resulted in the remapping of three loci, Atpb, Ly-5, and Pmv-24, as compared to the mouse linkage map. Two previously unmapped endogenous proviruses are also putatively assigned positions on the chromosome.

Animals↗
PubMed1990

Mutation of the core or adjacent LVb elements of the Moloney murine leukemia virus enhancer alters disease specificity.

Transcriptional enhancers of replication-competent mouse C-type retroviruses are potent determinants of the distinct disease-inducing phenotypes of different viral isolates and can also strongly influence the incidence and latent period of disease induction. To study the contribution of individual protein-binding sites to viral pathogenicity, we introduced mutations into each of the known nuclear factor-binding sites in the enhancer region of the Moloney murine leukemia virus and injected viruses with these mutations into newborn NFS mice. All viruses induced disease. Viruses with mutations in both copies of the leukemia virus factor a (LVa) site, leukemia virus factor c (LVc) site, or in just the promoter proximal copy of the glucocorticoid response element (GRE) had a latent period of disease onset and disease specificity indistinguishable from that of the wild-type Moloney virus. Viruses with mutations in two or three of the GREs, in both copies of the leukemia virus factor b (LVb) site, in two of the four nuclear factor 1 (NF1) consensus motifs, or in both copies of the conserved viral core element showed a significant delay in latent period of disease induction. Strikingly, viruses with mutations in the core element induced primarily erythroleukemias, and mutations in the LVb site also resulted in a significant incidence of erythroleukemias. These and other genetic and biochemical studies suggest models for how subtle alterations in the highly conserved structure of mouse C-type retrovirus enhancers can produce a dramatic effect on disease specificity.

Animals↗
PubMed1990

Alignment of U3 region sequences of mammalian type C viruses: identification of highly conserved motifs and implications for enhancer design.

We aligned published sequences for the U3 region of 35 type C mammalian retroviruses. The alignment reveals that certain sequence motifs within the U3 region are strikingly conserved. A number of these motifs correspond to previously identified sites. In particular, we found that the enhancer region of most of the viruses examined contains a binding site for leukemia virus factor b, a viral corelike element, the consensus motif for nuclear factor 1, and the glucocorticoid response element. Most viruses containing more than one copy of enhancer sequences include these binding sites in both copies of the repeat. We consider this set of binding sites to constitute a framework for the enhancers of this set of viruses. Other highly conserved motifs in the U3 region include the retrovirus inverted repeat sequence, a negative regulatory element, and the CCAAT and TATA boxes. In addition, we identified two novel motifs in the promoter region that were exceptionally highly conserved but have not been previously described.

Animals↗
PubMed1990

Point mutations in the Moloney murine leukemia virus enhancer identify a lymphoid-specific viral core motif and 1,3-phorbol myristate acetate-inducible element.

The transcriptional enhancer of the Moloney murine leukemia virus (MoMLV) is organized as a 75-base-pair repeat, and in each copy of the repeat there are multiple binding sites for nuclear factors. We have introduced point mutations into each of the known nuclear factor-binding sites in the MoMLV enhancer, in both copies of the direct repeat, and have analyzed the transcriptional activity conferred by the mutated enhancers by transient-expression assays in both hematopoietic and nonhematopoietic cell lines. Mutation of individual binding sites in the MoMLV enhancer has moderate effects (less than 2-fold to 20-fold) on transcription in six independent cell lines. Several mutations decreased transcription from the MoMLV enhancer ubiquitously (the leukemia virus factor b site and the glucocorticoid response element), whereas others affected transcription specifically in lymphoid cell lines (core motif) or, more significantly, in fibroblasts (nuclear factor 1 site). The transcriptional activity of the MoMLV enhancer can be induced 8- to 10-fold by 1,3-phorbol myristate acetate in Jurkat T cells. Mutations in any of three adjacent binding sites (leukemia virus factor b and c sites and the core motif) within a 28-base-pair region in the center of the direct repeat sequence of the MoMLV enhancer completely attenuate the response to 1,3-phorbol myristate acetate.

Animals↗
PubMed1990

cis-acting elements in the U3 region of a simian immunodeficiency virus.

A series of 5' deletions and a point mutation in the binding site for nuclear factor kappa B were introduced into the U3 region of a molecular clone of simian immunodeficiency virus from macaques (SIVmac142). The transcriptional activity of the mutated U3 regions was analyzed by transient chloramphenicol acetyltransferase assays. Two distinct regions in U3 appeared to contain important cis-acting sequences for transcriptional activity. Mutation of the single nuclear factor kappa B site in the SIVmac142 U3 region attenuated transcription in Rat-1 fibroblasts and Jurkat T cells. A second cis-acting element was localized to sequences between -162 and -114 in U3; deletion of long terminal repeat sequences up to -114 significantly attenuated transcriptional activity in Rat-1 cells. Furthermore, sequences between -162 and -114 contributed to inducibility of transcription by 1,3-phorbol myristate acetate in Jurkat T cells. Deletion of long terminal repeat sequences to -114, in addition to mutation of the nuclear factor kappa B site, was necessary to attenuate the response to 1,3-phorbol myristate acetate completely. A negative regulatory element analogous to that identified in the U3 region from the human immunodeficiency virus was not found in the U3 region from SIVmac142.

Animals↗
PubMed1989

Distinct segments within the enhancer region collaborate to specify the type of leukemia induced by nondefective Friend and Moloney viruses.

The nondefective Moloney and Friend murine leukemia viruses induce T-cell lymphomas and erythroleukemias, respectively, after being injected into newborn NFS mice. In previous studies, we showed that the distinct disease specificities of the two viruses could be switched by exchanging a small segment, about 200 nucleotides in length, encompassing their enhancer regions. This segment included the direct repeat sequence and an adjacent GC-rich region of about 20 nucleotides defined in studies of Moloney murine sarcoma virus enhancer-promoter function (L. A. Laimins, P. Gruss, R. Pozzatti, and G. Khoury, J. Virol. 49:183-189, 1984). The direct repeats of Friend and Moloney viruses are identical in a central core sequence of 32 nucleotides but have sequence differences on either side of this core as well as in their GC-rich segments. To determine whether disease specificity resides in part or in all of the direct repeat and GC-rich region, we constructed recombinants between Friend and Moloney viruses within this segment and tested them for their disease-inducing phenotypes. We found that disease specificity, in particular the ability of Friend virus sequence to confer erythroleukemogenicity on Moloney virus, is encoded throughout the region in at least three separable segments: the 5' and 3' halves of the direct repeat and the GC-rich segment. When just one of these segments (either both 5' halves of the direct repeat, both 3' halves, or just the GC-rich segment) from Friend virus was substituted into a Moloney virus genome, it conferred only a negligible or low incidence of erythroleukemia (less than or equal to 5% to between 10 and 15%). Any two segments together were considerably more potent (35 to 95% erythroleukemia), with the most effective pair being the two halves of the direct repeat. Individual segments and pairs of segments were considerably more potent determinants when they were matched with a genome of the same origin. Thus, although sequences outside the enhancer region are minor determinants of disease specificity when the enhancer is derived entirely from either Friend or Moloney virus, they can play a significant role when the enhancer is of mixed origin. Some recombinant enhancers conferred a long latent period of disease induction. This was particularly striking when the 5' halves of each copy of the direct repeat sequence were derived from Moloney virus and the 3' halves were derived from Friend virus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Nuclear factors that bind to the enhancer region of nondefective Friend murine leukemia virus.

Nondefective Friend murine leukemia virus (MuLV) causes erythroleukemia when injected into newborn NFS mice, while Moloney MuLV causes T-cell lymphoma. Exchange of the Friend virus enhancer region, a sequence of about 180 nucleotides including the direct repeat and a short 3'-adjacent segment, for the corresponding region in Moloney MuLV confers the ability to cause erythroid disease on Moloney MuLV. We have used the electrophoretic mobility shift assay and methylation interference analysis to identify cellular factors which bind to the Friend virus enhancer region and compared these with factors, previously identified, that bind to the Moloney virus direct repeat (N. A. Speck and D. Baltimore, Mol. Cell. Biol. 7:1101-1110, 1987). We identified five binding sites for sequence-specific DNA-binding proteins in the Friend virus enhancer region. While some binding sites are present in both the Moloney and Friend virus enhancers, both viruses contain unique sites not present in the other. Although none of the factors identified in this report which bind to these unique sites are present exclusively in T cells or erythroid cells, they bind to three regions of the enhancer shown by genetic analysis to encode disease specificity and thus are candidates to mediate the tissue-specific expression and distinct disease specificities encoded by these virus enhancer elements.

Animals↗
PubMed1987

Serial dexamethasone suppression tests in initial suppressors and nonsuppressors treated with electroconvulsive therapy.

Four different methods of quantifying the 1-mg Dexamethasone Suppression Test (DST) were contrasted with serial testing in endogenous depressives receiving electroconvulsive therapy (ECT). Of three continuous measures in 38 patients with pretreatment DSTs, only the log-transformed value for plasma cortisol was normally distributed, indicating that it possessed superior psychometric properties. Pretreatment Hamilton Depression Rating Scores (HAM-D) correlated positively with pretreatment DST status, with a similar association noted between posttreatment DST status and HAM-D scores. There was no uniform effect of ECT on the DST. Although pretreatment nonsuppressors showed a trend toward decreased postdexamethasone cortisol values, initial suppressors (cutoff: 5 micrograms/dl) evidenced a significant increase in these values, and 35.3% of initial suppressors were nonsuppressors at final DST assessment. These trends were noted in the DST assessment done following the third ECT treatment, suggesting an effect of regression to the mean. The findings highlight the importance of following initial DST suppressors in studies of this type.

Depressive Disorder↗