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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 415 records · Page 23Linked to original sources
PubMed1990

Requirements for simian immunodeficiency virus antigen-specific in vitro proliferation of T cells from infected rhesus macaques and sooty mangabeys.

The measurement of cell-mediated immunity against the etiologic agent of human AIDS (HIV) in the non-human primate model of AIDS (simian immunodeficiency virus, SIV) has been difficult. In general, culture of peripheral blood mononuclear cells from HIV-1- and SIV-infected humans and monkeys, respectively, with purified inactivated HIV and SIV virus preparations has given inconsistent or negative proliferative responses. However, we describe herein an assay which consists of coculturing monocytes that have been pulsed with inactivated SIVsmm with nylon-wool-purified autologous T cells, leading to antigen-specific T-cell proliferation. The proliferative response, which predominantly occurs in CD4+ T cells, is major histocompatibility complex (MHC) class II-restricted and requires antigen processing. This assay will greatly facilitate the identification of the immunodominant epitopes recognized by T cells in sooty mangabeys, which are naturally infected but remain clinically asymptomatic, and in rhesus macaques, in which experimental infection leads to clinical symptomatology similar to human AIDS, eventually resulting in death.

Animals↗
PubMed1990

A comparison of venous versus capillary measurements of drug concentration.

Accessing patient's veins for drug level sampling is not always feasible. The use of capillary sampling techniques is often utilized when venous access is hampered. In the therapeutic monitoring of patients, unexpected drug level results often occur that can be caused by a number of different factors. The possibility that differences in assay results might occur if samples were collected by capillary stick vs. venous phlebotomy was examined by simultaneous sampling in 18 patients. Although correlation was very high (0.999) and percentage differences fairly low (range of 0 to 15.4%), a statistical difference was noted in the sampling methods. The precision was 6.5 +/- 6.58% and there was a slight negative bias (-3.76%), with capillary samples less than venous samples. Although there were statistical differences for the drugs studied in the concentration ranges evaluated, capillary samples should provide fairly small errors when compared to venous samples.

Adult↗
PubMed1990

Unsatisfactory colposcopy and the response to orally administered oestrogen: a randomized double blind placebo controlled trial.

Thirty-six women with dyskaryotic cervical smears and unsatisfactory colposcopy were randomly allocated to receive either 30 micrograms ethinyl oestradiol or placebo daily by mouth for 10 days. Thirty-four women were available for review (17 women in each of the two groups), full colposcopic inspection of the transformation zone was possible in a significantly greater proportion of the oestrogen treated group (70% versus 23%, P less than 0.01). As most diagnostic conizations are currently performed on the basis of unsatisfactory colposcopy, the use of oestrogen medication followed by colposcopic reassessment should permit a reduction in the number of patients subject to operation.

Adult↗
PubMed1990

Nucleolar organiser regions in adenocarcinoma in situ and invasive adenocarcinoma of the cervix.

Silver binding nucleolar regions (AgNORs) were evaluated in normal endocervix, adenocarcinoma, and its potential precursor, adenocarcinoma in situ (AIS), in an attempt to increase an understanding of the natural history of cervical adenocarcinoma and to identify a marker for abnormal endocervical (atypical glandular) cells which could aid diagnosis and follow up of endocervical lesions. For every 50 cells the mean AgNOR counts were as follows: normal endocervical cells (n = 15) 79.8 (95% Cl 68-91); AIS (n = 20) 200.7 (95% Cl 182-219); and invasive adenocarcinoma (n = 30) 299 (271-328). There was no overlap between the groups of normal endocervical cells and invasive adenocarcinoma, but there was significant overlap between cases of invasive adenocarcinoma and carcinoma in situ. In six out of 17 cases with AIS, NOR count in adjacent morphologically normal glandular cells ("internal" controls) was increased when compared with the "external" (normal endocervical) control group. This suggests the presence of wider field changes not previously identified using routine histological methods. The findings suggest that AIS is a potential premalignant precursor of invasive adenocarcinoma, but that assessment of NORs is of no practical use in discriminating between the histological types of cervical carcinoma.

Adenocarcinoma↗
PubMed1990

Analysis of chromosomal aberrations in workers exposed to low level benzene.

Metaphase chromosome preparations were analysed as part of a larger study from a population occupationally exposed to benzene and compared with a control group. Forty eight of the 66 exposed individuals and 29 of the 33 controls had samples in which metaphase spreads could be evaluated. The incidence of chromosomal aberrations (particularly chromatid deletions and gaps) in the exposed group were slightly increased compared with the control group. This increase was of borderline significance in parametric statistical tests but was significant using Fisher's exact test. No lifestyle factors had any consistent effect on the incidence of chromosome aberrations, although there was a small reduction in gaps with increasing cigarette smoking. Older individuals had a higher incidence of chromosome exchanges and "other" aberrations. Individuals who reported a recent viral illness had a higher incidence of aberrations particularly gaps. There was no evidence of any correlation in the incidence of chromosome aberrations with any of the other biological parameters previously reported. The increased incidence of aberrations seen in the group exposed to benzene may result from a history of exposure to benzene. Nevertheless, other explanations such as sampling, interindividual variability, and unintentional bias in the selection of two groups cannot be excluded.

Benzene↗
PubMed1990

Effects of methyl isocyanate on rat brain cells in culture.

Since the disaster in Bhopal, India, people exposed to methyl isocyanate (MIC) have complained of various disorders including neuromuscular dysfunction. In an attempt to get information about such dysfunction we have previously shown that MIC can affect muscle cells in culture. The present communication reports investigations into the effect of MIC on brain cells in culture. MIC was toxic to brain cells and the response was dose related. The observations were supported by light and electron microscopy.

Animals↗
PubMed1990

In vitro models.

The development of in vitro models is advancing rapidly, with the application of cell culture methods as an alternative to animals in toxicological screening; non-cellular systems are also being used. Any screening test, whether for detecting irritants, carcinogens or teratogens should be well validated against known animal studies. It should, for example, be able to correctly identify a teratogen as well as a non-teratogen. Various types of in vitro systems are utilised. Some validated test systems have been used for several years to detect genotoxins and are acceptable to many regulatory authorities. This is not the case for other in vitro systems, although some for skin irritation and corrosion are acceptable to some authorities. A non-comprehensive range of tests to measure responses in ocular, immune, cardiac, vascular, neurological, sensory, hepatic, testicular and embryological systems are described. Some tests are empirical and others much more closely mimic the animal model they represent. Some of the methods described are much closer to validation than others.

Animals↗
PubMed1990

Chinese hamster ovary (CHO/HPRT) cell mutation assays with EMS, benzo[a]pyrene and benzidine.

In the context of the third UKEMS collaborative trial on cell mutation assays, three chemicals have been tested for mutagenicity using the Chinese hamster ovary (CHO) cell/HPRT assay. The protocol employed was based on the re-spreading of monolayer cultures, maintaining one million cells in growth for an expression time of 7 days. Ethyl methanesulphonate gave clear and consistent positive results in the absence of S9 and a clear response to benzo[a]pyrene was obtained with 1% S9. Benzidine gave no evidence of mutagenicity either with or without S9. The results show that the CHO/HPRT assay protocol used in this study is adequate for the detection of potent mutagens. The failure to detect benzidine as a mutagen may be due either to a basic unresponsiveness of the system or to a lack of sensitivity because of the limitation on the numbers of cells which can be maintained during expression. Statistical analysis showed that significant variation occurred between cell survival and mutagenicity estimates for replicate cultures, demonstrating the need for duplicate cultures.

Animals↗
PubMed1990

A report of eight HIV-seropositive patients with major depression responding to fluoxetine.

This pilot study examined the effectiveness of fluoxetine in depressed human immunodeficiency virus (HIV)-seropositive asymptomatic patients. Eight patients, participating in an AZT trial who met criteria for major depression syndrome (DSM-III-R), were treated with fluoxetine (20 or 40 mg/day) for 4 weeks. Initially, mean Hamilton Depression scores were 23.8 (range of 17-31), and improved to 6.4 (range of 3-10). All subjects maintained their remission over a 2-month follow-up. Fluoxetine treatment may be effective in treating major depression in HIV-seropositive asymptomatic patients.

Adult↗
PubMed1990

The use of short-term tests in detecting carcinogenicity of complex mixtures.

Since it is not feasible to test all substances in long-term animal studies, short-term tests for DNA damage, gene mutation, aneuploidy, chromosomal damage and cell transformation performed in prokaryotes and eukaryotes in vitro and in vivo are used to test pure chemicals and mixtures. Understanding the contribution of mutagens in air, water and food is important to our way of life; methods of sampling and testing such mutagens are discussed in this review.

Air Pollutants↗
PubMed1990

A novel mast cell growth factor (MCGF-3) produced by marrow-adherent cells that synergizes with interleukin 3 and interleukin 4.

A clonal marrow-adherent stromal cell line, +/+-1 LDA11, was derived and found to produce hemopoietic stimulatory activity for an interleukin 3 (IL-3)-dependent mast cell line, NFS/N1. This factor-dependent mast cell line displayed restricted growth factor responsiveness to only IL-3, interleukin 4 (IL-4), and the stromal cell-produced factor. The factor produced by stromal cells was distinguished from IL-3 and IL-4 and was characterized biochemically. This factor appears to be a novel mast cell growth factor (MCGF-3) capable of synergizing with IL-3 and IL-4. It may have broader reactivity in hemopoiesis than simply IL-3-dependent mast cells, and it may prove relevant to stromal cell-mediated hemopoiesis.

Animals↗
PubMed1989

The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms.

Receptors for interleukin-4 (IL-4) are expressed at low levels on a wide variety of primary cells and cultured cell lines. Fluorescence-activated sorting of CTLL-2 cells resulted in the isolation of a subclone, CTLL 19.4, which expressed 10(6) IL-4 receptors per cell. These cells were used for the purification of IL-4 receptor protein and to prepare a hybrid-subtracted cDNA probe for isolation of cDNA clones. Three classes of IL-4 receptor cDNA were identified. The first encoded a 140 kd membrane bound IL-4 receptor containing extracellular, transmembrane, and cytoplasmic domains. The second class lacked the cytoplasmic region, and the third encoded a secreted form of the receptor. All cDNA clones expressed in COS-7 cells had IL-4 binding properties comparable to the native IL-4 receptor. The soluble form of the IL-4 receptor blocked the ability of IL-4 to induce CTLL cell proliferation and may represent a regulatory molecule specific for IL-4-dependent immune responses.

Amino Acid Sequence↗
PubMed1989

In vitro packaging of bacteriophage phi 29 DNA restriction fragments and the role of the terminal protein gp3.

Restriction fragments of bacteriophage phi 29 DNA-gp3 (DNA-gene product 3 complex) were packaged in a completely defined in vitro system that included purified proheads, the DNA packaging protein gp16 and ATP. Both left and right end DNA-gp3 fragments were packaged in this system, in contrast to the oriented and selective packaging of left end DNA-gp3 fragments in extracts; left ends could be packaged quantitatively in the defined system, while the packaging efficiency of right ends was generally about threefold lower. In addition, certain internal (non-end) DNA fragments were packaged at efficiencies of about 10% to 15%. Digestion of the gp3 with trypsin or proteinase K reduced the packaging of whole-length DNA by a factor of 2 or 4, respectively, and removal of the gp3 from whole-length DNA or end fragments with piperidine reduced packaging to the level of internal fragments. Though the terminal protein gp3 was non-essential for DNA translocation in the defined system, it stimulated packaging of left and right end fragments, and stabilized packaging of the left end. The packaging of end and internal DNA fragments of the related phage M2Y into phi 29 proheads was similar to that of phi 29 DNA fragments, and certain fragments of lambda DNA were packaged at the efficiency of the internal phi 29 DNA fragments. Selective packaging of DNA-gp3 left ends was restored by the addition of bacterial cell extracts or glycerol to the defined system, and these packaging conditions discriminated between phi 29 and M2Y DNAs that have distinct terminal proteins.

Bacillus subtilis↗