Pre-ejaculatory fluid as potential vector for sexual transmission of HIV-1.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
D Anderson
Publications and source records attributed to D Anderson.
Supercoiled DNA wraps around the bacteriophage phi 29 head-tail connector.
Supercoiled pBR322 DNA wraps around the outside of the isolated Bacillus subtilis bacteriophage phi 29 head-tail connector, the crux of the DNA packaging machine of the viral precursor capsid or prohead. The contour length of the supercoiled DNA, determined by EM, decreased by approximately 180 base pairs for each connector bound. Mass and radial density determinations by scanning transmission EM showed that the increased mass of the connector-DNA complex relative to the connector alone was equivalent to approximately 170 base pairs of DNA and was located around the outside of the connector. Topoisomerase I treatment of the complexes followed by deproteinization suggested that supercoils were restrained by the connectors. Connectors bound linear and open-circular plasmid DNAs inefficiently but were not wrapped by these DNAs. The wrapping of supercoiled DNA around the isolated phi 29 connector is hypothesized to reflect the initiation phase of the normal process of DNA packaging. Packaging substrates would be supercoiled, wrapped by the connector, linearized, and translocated by rotation of the connector relative to the viral capsid with the aid of ATP hydrolysis.
Bacillus Phages↗
The association of insulin-elicited phosphotyrosine proteins with src homology 2 domains.
The interactions of the phosphotyrosine (Tyr(P))-containing proteins in basal and insulin-stimulated 3T3-L1 adipocytes with src homology 2 (SH2) domains from phosphatidylinositol 3-kinase (PI3K), ras GTPase-activating protein (GAP), and phospholipase C gamma have been examined. The Tyr(P) forms of the insulin receptor and its 160-kDa substrate protein (pp160) associated with fusion proteins containing either or both the SH2 domains of PI3K, but not with fusion proteins containing the two SH2 domains of GAP or phospholipase C gamma. These results demonstrate a specificity for the association of the Tyr(P) form of the insulin receptor and pp160 with SH2 domains that parallels the reported effects of insulin on PI3K, GAP, and phospholipase C gamma in vivo. Immunoprecipitates of pp160 from the cytosol of insulin-treated, but not basal, 3T3-L1 adipocytes contained PI3K activity. Moreover, the Tyr(P) form of pp160 with associated PI3K activity migrated at 10 S on a sucrose velocity gradient, whereas the Tyr(P) form without associated activity migrated at 6 S. These findings indicate that the Tyr(P) form of pp160 associates directly with PI3K in vivo.
3T3 Cells↗
Synthesis and in vitro characterization of novel amino terminally modified oxotremorine derivatives for brain muscarinic receptors.
A series of novel 2-substituted acetylenic pyrrolidines and piperidines related to oxotremorine (1) were prepared and evaluated in vitro as muscarinic cholinergic agents at brain M1 and M2 receptors. One analogue, 3-(2-oxo-1-pyrrolidinyl)-1-[2(R)-pyrrolidinyl]-1-propyne hydrogen oxalate (6a), was found to be a partial agonist producing a PI hydrolysis response at cortical M1 receptors approximately 3-fold larger than that produced by 1. The intrinsic activity profile of 6a at brain muscarinic receptors is similar to those of azetidine oxo analogue 2 and dimethylamino oxo analogue. All three compounds are partial M1 agonists and full M2 agonists; however, the profile of 6a in binding studies is significantly different. While 2 and 3 exhibit large M2 selectivities ranging between 8-fold to several hundred-fold, the binding profile of 6a shows almost no subtype selectivity.
Animals↗
Mutant prohead RNAs in the in vitro packaging of bacteriophage phi 29 DNA-gp3.
The 174-base prohead RNA encoded by bacteriophage phi 29 of Bacillus subtilis, essential for packaging of the DNA-gp3 (DNA-gene product 3) complex, was expressed efficiently from the cloned gene. Computer programs for RNA structure analysis were used to fold hypothetical RNA mutants and thus to target mutagenesis of the RNA for studies of structure and function. Five mutants of the RNA were then produced by oligonucleotide-directed mutagenesis that were altered in the primary sequence at selected sites; two of these mutants were predicted to be altered in secondary structure from a model established previously by a phylogenetic analysis. The binding of the 32P end-labeled mutant RNAs to RNA-free proheads was comparable with that of the wild-type RNA. However, the capability of the mutant RNAs to reconstitute RNA-free proheads for DNA-gp3 packaging in the defined in vitro system and for assembly of phage in RNA-free extracts was variable, depending upon the alteration. Changes of highly conserved bases that retained the predicted secondary structure of the RNA model were tolerated to a much greater extent than changes predicted to alter the RNA secondary structure.
Bacteriophages↗
Anomalous effect of mazindol on dopamine uptake as measured by in vivo voltammetry and microdialysis.
The effect of mazindol on the dopamine (DA) uptake system in the rat striatum was studied by in vivo voltammetry and microdialysis. An increase in the maximal uptake rate was observed by voltammetry 30 min after i.p. administration of 1, 5, 10, 15, and 20 mg/kg doses but not after a dose of 25 mg/kg, while stimulated release was enhanced at all doses. The increased maximal uptake is in contrast to increased levels of extracellular DA observed with microdialysis following mazindol administration. This divergence of action is anomalous in the context of current understanding of the DA uptake system.
Animals↗
Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection.
Studies were undertaken to determine whether interleukin 10, (IL-10) a cytokine shown to inhibit interferon gamma (IFN-gamma) production, was involved in Trypanosoma cruzi infections in mice. Exogenous IFN-gamma protects mice from fatal infection with T. cruzi. Furthermore, resistant B6D2 mice developed fatal T. cruzi infections when treated with neutralizing anti-IFN-gamma monoclonal antibody (mAb). Thus, endogenous as well as exogenous IFN-gamma is important in mediating resistance to this parasite. Because both T. cruzi-susceptible (B6) and -resistant (B6D2) mouse strains produced IFN-gamma during acute infection, we looked for the concomitant production of mediators that could interfere with IFN-gamma-mediated resistance to T. cruzi. We found that IL-10-specific mRNA was produced in the spleens of mice with acute T. cruzi infections. In addition, spleen cell culture supernatants from infected B6 mice, and to a lesser extent B6D2 mice, elaborated an inhibitor(s) of IFN-gamma production. This inhibitor(s) was neutralized by anti-IL-10 mAb. These experiments demonstrated the production of biologically active IL-10 during T. cruzi infection. In further studies in vitro, it was shown that IL-10 blocked the ability of IFN-gamma to inhibit the intracellular replication of T. cruzi in mouse peritoneal macrophages. Thus, in addition to its known ability to inhibit the production of IFN-gamma, IL-10 (cytokine synthesis inhibitory factor), may also inhibit the effects of IFN-gamma. These experiments demonstrate that IL-10 is produced during infection with a protozoan parasite and suggest a regulatory role for this cytokine in the mediation of susceptibility to acute disease.
Animals↗
The comparative concurrent validities of the Shipley Institute of Living Scale and the Henmon-Nelson Tests of Mental Ability.
This study compared the abilities of the Shipley Institute of Living Scale and the Henmon-Nelson Tests of Mental Ability to predict Wechsler Adult Intelligence Scale-Revised (WAIS-R) scores in psychiatric hospital patients. The Henmon-Nelson DIQs accounted for about 50% more WAIS-R Verbal and Full Scale IQ variance than did the Shipley IQs, apparently because of their higher correlations with the Information, Vocabulary, and, perhaps, Similarities subtests. Because Henmon-Nelson scores were more variable and generally higher than their WAIS-R counterparts, statistical adjustments were needed to optimize Wechsler IQ estimates. Therefore, regression formulae and a conversion table for the estimation of WAIS-R Full Scale IQs from Henmon-Nelson and Shipley intelligence scores also are presented.
Adult↗
Recombinant murine steel factor stimulates in vitro production of granulocyte-macrophage progenitor cells.
The ability of murine Steel factor to promote the in vitro production of granulocyte-macrophage progenitor cells (CFU-GM) was examined in short-term liquid cultures. Bone marrow from C57BL/6J or Sl/Sld mice was placed in culture for seven days with either Steel factor alone or in the presence of IL-3. CFU-GM responsive to GM-CSF, IL-3, and CSF-1 were measured in the input population and again after 3 or 7 days in culture. Steel factor alone increased the number of all CFU-GM types as early as 3 days after culture initiation, with further increases at day 7. This effect was potentiated by the addition of IL-3. Production of CFU-GM by C57BL/6J or Sl/Sld marrow was comparable except for enhanced production of CSF-1 responsive progenitors by Sl/Sld marrow. A recombinant Sld protein was also shown to be equivalent to the wild-type protein in its capacity to promote CFU-GM production from normal bone marrow.
Animals↗
Thioguanine-resistant mutant frequency in T-lymphocytes from a healthy human population.
Resistance to 6-thioguanine in T-lymphocytes was used to study in vivo somatic mutations in normal healthy adults. Donor age had a significant effect on mutant frequency at the hprt locus, showing an increase of 0.09/10(6) cells per year of age. No significant increase was associated with sex of donor, smoking habits, alcohol or coffee/tea intake, or X-ray exposure. The lower mutant frequency seen with contraceptive pill usage was probably due to the age difference between the groups of users and non-users.
Adult↗
Prolonged ambulatory monitoring of colonic motor activity in the pig.
The aim of this study was to develop a chronic model suitable for repeated, long-term studies of the interaction of behavior and colonic function in unrestrained pigs. Cecostomies were created in three 20-30 kg micropigs under general anesthesia. Fistulas were created by suturing the bowel to the abdominal wall. Recordings were made by passing a small (8F) solid-state pressure transducer through the fistula into the proximal bowel and connecting it to a battery-operated data logger worn in a vest on the pig's back. Cecostomies have remained patent and trouble-free for over 18 months. No serious infections have occurred. Preliminary data from a total of thirteen 24-h recording sessions showed 54% of all contractile activity to be in the 2-4 cpm frequency range. Increased motility was seen following meals and upon morning awakening. Motility was minimal during the night. Infrequent (10.31 +/- 2.05/24 h; mean +/- SD) propagated contractions were also noted. These contractions were generally of low amplitude (33.24 +/- 3.81 mmHg). These techniques allow prolonged, intraluminal recordings to be made from the colon of the unrestrained pig.
Animals↗
Effects of dietary imbalances on spermatogenesis in CD-1 mice and CD rats.
Nutritional toxicology is now a well established discipline for somatic cells, but no such approach is widely used yet in studies of reproductive toxicology. Reduced dietary intake in mice is known to impair spermatogenesis, and animals in toxicity studies frequently show reduced food intake after dosing. Furthermore, although many human groups have nutritionally inadequate diets, the impact of dietary imbalances on the reproductive system has not been systematically examined. A series of experiments was conducted to dissect the spermatogenic response to dietary alterations in mice and rats. It was found that in mice, the increase in abnormal sperm after such treatment was the result of a lack of calories, while the decrease in sperm counts may have been caused by a lack of protein. In rats, dietary restriction was found only to deplete sperm numbers, probably because of a lack of calories and/or non-energetic components of the diet. Additionally, it was shown that a protein-free diet causes a multiplicity of effects on germ cells, some of which are different in mice and rats. A low-fat diet had an adverse effect on sperm numbers and a similar, but much more pronounced effect was observed in both species fed a carbohydrate-free diet. These alterations of spermatogenic endpoints and the species differences observed, have considerable implications for reproductive toxicology.
Administration, Oral↗
"Primatization" of recombinant antibodies for immunotherapy of human diseases: a macaque/human chimeric antibody against human CD4.
Immunoglobulin variable region genes from non-human primates, cynomolgus macaques, were shown to have 85%-98% homology with human immunoglobulin sequences and yet macaques are phylogenetically distant enough to respond against conserved human antigens. Immunoglobulin genes were isolated from monkeys immunized with human CD4 antigen and a human/monkey chimeric anti-CD4 antibody with 91-92% homology to human immunoglobulin framework regions was cloned and expressed. The antibody has an apparent affinity of 3.2 x 10(-11) M and exhibits potent immunosuppressive properties in vitro.
Animals↗
[Modification of in vitro motility of human sperm by various dioxin congeners in super-physiologic concentrations].
Human ejaculate was fractionated using density gradient centrifugation. Highly motile spermatozoa were incubated with "superphysiological" concentrations of various dioxin congeners. Over a period of sixty hours, no relevant influence on sperm motility in comparison to control media was noted on triplicate testing. It therefore appears unlikely, that intravaginally ejaculated spermatozoa would be compromised in their motility by naturally occurring levels of dioxins in female genital tract secretions. However, this does not preclude the possibility of such dioxin levels affecting normal intratesticular spermatogenesis.
Dioxins↗
Childhood psychological trauma correlates with unsuccessful lumbar spine surgery.
In a retrospective study of 86 patients who underwent lumbar spine surgery, patients who had three or more of a possible five serious childhood psychological traumas (risk factors) had an 85% likelihood of an unsuccessful surgical outcome. Conversely, in patients with a poor surgical outcome, the incidence of these traumas was 75%. In the group of 19 patients with no risk factors, there was only a 5% incidence of failure. This study shows that a highly significant correlation exists between unsuccessful lumbar spine surgery and a history of childhood traumas. Although recognition of predictors for unsuccessful outcome can be useful in avoiding surgery in patients whose indications for surgery are borderline, the greater challenge is to help the patient who, despite being at high psychological risk for negative outcome, has severe spinal pathology that will likely require surgery. In such cases, psychiatric treatment is critical. In the group of 19 patients with no risk factors, single-level laminectomies and discectomies were performed on 6 patients. The other 13 cases were complex, involving a combination of repeat surgeries (n = 4) fusions (n = 3), and/or multilevel laminectomies and discectomies (n = 11).
Adult↗
Multiple SH2-mediated interactions in v-src-transformed cells.
The Src homology 2 (SH2) domain is a noncatalytic region which is conserved among a number of signaling and transforming proteins, including cytoplasmic protein-tyrosine kinases and Ras GTPase-activating protein (GAP). Genetic and biochemical data indicate that the SH2 domain of the p60v-src (v-Src) protein-tyrosine kinase is required for full v-src transforming activity and may direct the association of v-Src with specific tyrosine-phosphorylated proteins. To test the ability of the v-Src SH2 domain to mediate protein-protein interactions, v-Src polypeptides were expressed as fusion proteins in Escherichia coli. The bacterial v-Src SH2 domain bound a series of tyrosine-phosphorylated proteins in a lysate of v-src-transformed Rat-2 cells, including prominent species of 130 and 62 kDa (p130 and p62). The p130 and p62 tyrosine-phosphorylated proteins that complexed v-Src SH2 in vitro also associated with v-Src in v-src-transformed Rat-2 cells; this in vivo binding was dependent on the v-Src SH2 domain. In addition to binding soluble p62 and p130, the SH2 domains of v-Src, GAP, and v-Crk directly recognized these phosphotyrosine-containing proteins which had been previously denatured and immobilized on a filter. In addition, the SH2 domains of GAP and v-Crk bound to the GAP-associated protein p190 immobilized on a nitrocellulose membrane. These results show that SH2 domains bind directly to tyrosine-phosphorylated proteins and that the Src SH2 domain can bind phosphorylated targets of the v-Src kinase domain.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.
The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors.
Animals↗
Cognitive-behavioural treatment of panic disorder during pregnancy and lactation.
The treatment of panic disorder during pregnancy and lactation poses special problems. It is important that both the practitioner and patient consider a number of issues to find the most appropriate treatment for the patient. New cognitive-behavioural treatment options often circumvent the problems of pharmacotherapy for pregnant or lactating women while providing therapeutic benefits which are at least equivalent.
Adult↗