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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 379 records · Page 21Linked to original sources
PubMed1991

Molecular cloning and expression of the type 1 and type 2 murine receptors for tumor necrosis factor.

Clones encoding the type 1 (p80) and type 2 (p60) forms of the murine receptors for tumor necrosis factor (TNF) were isolated by cross-hybridization using probes derived from the cloned human TNF receptors. Each of the murine receptors shows strong sequence homology to the corresponding human receptor (approximately 65% amino acid identity) throughout the molecule but only modest homology, limited to ligand-binding domains, between themselves. The ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs: both receptor types bind TNF-alpha and -beta with multiple affinity classes, and the ligands cross-compete. Analysis of the murine transcripts encoding these receptors revealed the presence of RNAs for one or both forms of the receptors in all cells examined. It was also demonstrated that for both types of human TNF receptor, variably sized transcripts are observed in different cells. The murine cDNAs were further used to determine the chromosomal locations of the TNF receptor genes. They are not linked, in contrast to the ligands, and map to chromosomes 4 (type 1) and 6 (type 2).

Amino Acid Sequence↗
PubMed1991

Acanthamoeba keratitis: experience in a non-specialist microbiology laboratory.

Acanthamoeba keratitis is an unusual complication of wearing soft contact lenses: a case was diagnosed by culturing corneal scrapings. Acanthamoeba are tolerant of variations in osmolarity in the culture media. Page's saline, recommended for culture agar plates, can easily be substituted with salines which are suitable for cell culture media, thereby avoiding the cumbersome manufacture of special saline. Early diagnosis as a result of successful isolation may avoid the need for keratoplasty.

Acanthamoeba↗
PubMed1991

The toxicity of benzene and its metabolism and molecular pathology in human risk assessment.

Benzene, a common industrial chemical and a component of gasoline, is radiomimetic and exposure may lead progressively to aplastic anaemia, leukaemia, and multiple myeloma. Although benzene has been shown to cause many types of genetic damage, it has consistently been classified as a non-mutagen in the Ames test, possibly because of the inadequacy of the S9 microsomal activation system. The metabolism of benzene is complex, yielding glucuronide and sulphate conjugates of phenol, quinol, and catechol, L-phenylmercapturic acid, and muconaldehyde and trans, trans-muconic acid by ring scission. Quinol is oxidised to p-benzoquinone, which binds to vital cellular components or undergoes redox cycling to generate oxygen radicals; muconaldehyde, like p-benzoquinone, is toxic through depletion of intracellular glutathione. Exposure to benzene may also induce the microsomal mixed function oxidase, cytochrome P450 IIE1, which is probably responsible for the oxygenation of benzene, but also has a propensity to generate oxygen radicals. The radiomimetic nature of benzene and its ability to induce different sites of neoplasia indicate that formation of oxygen radicals is a major cause of benzene toxicity, which involves multiple mechanisms including synergism between arylating and glutathione-depleting reactive metabolites and oxygen radicals. The occupational exposure limit in the United Kingdom (MEL) and the United States (PEL) was 10 ppm based on the association of benzene exposure with aplastic anaemia, but recently was lowered to 5 ppm and 1 ppm respectively, reflecting a concern for the risk of neoplasia. The American Conference of Governmental Industrial Hygienists (ACGIH) has even more recently recommended that, as benzene is considered an A1 carcinogen, the threshold limit value (TLV) should be decreased to 0.1 ppm. Only one study in man, based on nine cases of benzene associated fatal neoplasia, has been considered suitable for risk assessment. Recent re-evaluation of these data indicated that past assessments may have overestimated the risk, and different authors have considered that lifetime exposure to benzene at 1 ppm would result in an excess of leukaemia deaths of 9.5 to 1.0 per 1000. Although in this study, deaths at low levels of benzene exposure were associated with multiple myeloma and a long latency period, instead of leukaemia, which might justify further lowering of the exposure limit, the risk assessment model has been found to be non-significant for response at low levels of exposure. The paucity of data for man, the complexity of the metabolic activation of benzene, the interactive and synergistic mechanisms of benzene toxicity and carcinogenicity, the different disease endpoints (aplastic anaemia, leukaemia, and multiple myeloma), and different individual susceptibilities, all indicate that in such a complex scenario, regulators should proceed with caution before making further changes to the exposure limit for this chemical.

Anemia, Aplastic↗
PubMed1991

Studies on the mutagenicity of a zinc oxide-hexachloroethane smoke.

1. A suitable method has been developed for generating atmospheres of zinc oxide/hexachloroethane smoke (ZnHCE). 2. The smoke was investigated using the Ames test and the micronucleus assay. 3. It was weakly mutagenic to the bacteria, but in the bone marrow no increases in micronuclei were detected up to toxic levels of the smoke. 4. The method used here could be applied to other pyrotechnic mixtures which give rise to complex mixtures of products.

Animals↗
PubMed1991

Structured clinical teaching strategy.

This study investigated the impact of a structured exercise on low back pain, as part of a second year ambulatory course, on students' low back pain examination skills. One-hundred and eighty-eight medical students participated in one of four types of instructional intervention: 1) structured clinical exercise and reading, 2) random clinical experience and no reading, 3) reading only, and 4) no clinical experience or reading. At the end of the year, students completed an Objective Structured Clinical Exam (OSCE) in which two stations assessed back pain history and physical exam skills. An analysis of variance of the OSCE scores showed no significant difference in students' performance in relation to the type of instructional intervention. The General Professional Education of the Physician Report argues for the importance of structured clinical education. In medical education, unpredictable patient exposure and crowded curricula frequently result in students having none or only one structured learning opportunity to acquire critical skills. Unfortunately, this study found that assuring at least one structured clinical experience for a specific common problem seen in ambulatory care did not enhance student ability to select and use specific history or physical exam skills for that problem as assessed by an OSCE, as compared with students who did not have this experience. To assure that essential clinical skills are acquired, it most likely requires that both systematic instructional strategies and repeated learning opportunities are available to reinforce learning.

Ambulatory Care↗
PubMed1991

Influence of murine mast cell growth factor (c-kit ligand) on colony formation by mouse marrow hematopoietic progenitor cells.

Purified natural and recombinant murine mast cell growth factor (MGF, a c-kit ligand) were evaluated alone and in combination with other cytokines for effects in vitro on colony formation by multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells from BDF1 mouse bone marrow. Both preparations stimulated Epo-dependent CFU-GEMM and enhanced Epo-dependent BFU-E colony numbers and size. MGF had some stimulating activity for CFU-GM. When used in combination with plateau concentrations of pokeweed mitogen mouse spleen cell conditioned medium or granulocyte-macrophage colony stimulating factor (CSF), MGF enhanced in greater than additive fashion colony formation by CFU-GM. MGF also enhanced the size of colonies formed, an enhancement greatest for colonies containing granulocytes and macrophages. MGF did not enhance Macrophage-CSF stimulated colony numbers or size. MGF seems to be an early acting cytokine with preferential effects on the growth of more immature hematopoietic progenitor cells.

Animals↗
PubMed1991

The automated modified Russell viper venom time test for the lupus anticoagulant.

Antiphospholipid antibodies, both anticardiolipin antibody and lupus anticoagulant, are associated with a hypercoagulable state, manifested as thrombotic events and pregnancy losses. Multiple coagulation tests are available for the lupus anticoagulant, but few are in wide use. The modified Russell viper venom test (RVVT) is one of several excellent tests for the lupus anticoagulant, with high sensitivity and specificity. We present an automated method for measuring the RVVT and demonstrate its reproducibility.

Automation↗
PubMed1991

Stretch-based relaxation and the reduction of EMG activity among masticatory muscle pain patients.

This study explored the efficacy of stretch-based relaxation procedures for the reduction of muscle activity in the masseter regions of subjects diagnosed with masticatory muscle pain disorders. Thirty-four subjects with elevated masseter activity were assigned randomly to either a postural relaxation/rest experimental group or a stretch-based relaxation experimental group. Following a psychosocial stressor and application of the relaxation procedure, persons in the stretch-based group showed greater reductions in EMG activity than did those in the postural group for the right masseter region (t = 1.94, P less than .04) and the left masseter region (t = 2.07, P less than .03). The results are discussed in terms of the implications of these findings for further research concerning the etiology and treatment of masticatory muscle pain.

Adult↗
PubMed1991

Effectiveness of chlorhexidine and sodium fluoride in reducing dentin hypersensitivity.

This investigation was conducted to evaluate the effect of chlorhexidine, sodium fluoride, and sequential rinses of chlorhexidine (Cx) and sodium fluoride (NaF) on dentin hypersensitivity. Forty-four adult patients with dentin hypersensitivity on three teeth were randomly assigned to receive one of four treatment rinses: (1) placebo; (2) 0.12% Cx; (3) 0.2% NaF; or (4) 0.12% Cx plus 0.2 NaF. Patients' responses to cold stimulation were recorded at baseline, two weeks, and four weeks. Pain response was quantified by applying successively decreasing temperature intervals of water (20 degrees C, 15 degrees C, 10 degrees C, 5 degrees C, and 0 degrees C) to exposed dentin. Plaque Index (Silness and Löe) was recorded at baseline only. Data on dentin sensitivity over time were analyzed using a repeated measures ANOVA. This ANOVA was conducted to generate an error term for calculation of Dunn's multiple mean comparison test. A Spearman rank order test was computed to assess correlation between plaque and hypersensitivity at baseline. Results showed the Cx and NaF rinses alone significantly reduced hypersensitivity (p less than .01) at four weeks compared to baseline. Sequential Cx and NaF rinses significantly decreased sensitivity (p less than .01) at both the two- and four-week intervals compared to baseline. At the four-week interval, the sequential Cx/NaF rinse group showed a significantly greater reduction (p less than .01) in hypersensitivity response when compared to placebo. Cx alone, or NaF alone groups. A moderate, positive correlation (r = 0.55) was demonstrated between plaque and dentin hypersensitivity. This was statistically significant at the (p less than .05) level.

Adult↗
PubMed1991

Orchitis and human immunodeficiency virus type 1 infected cells in reproductive tissues from men with the acquired immune deficiency syndrome.

Mechanisms underlying human immunodeficiency virus type 1 (HIV-1) infection of the male reproductive tract and the sexual transmission of HIV-1 through semen are poorly understood. To address these issues, the authors performed morphologic and immunocytochemical analyses of reproductive tissues obtained at autopsy from 43 male acquired immune deficiency syndrome (AIDS) patients. Monoclonal antibodies recognizing different subpopulations of white blood cells were used to detect leukocyte infiltration and map the location of potential lymphocytic/monocytic HIV-1 host cells and immunocytochemistry and in situ hybridization techniques were used to detect HIV-1-infected cells in the testis, excurrent ducts, and prostate. Distinct pathologic changes were observed in a majority of testes of AIDS patients that included azoospermia, hyalinization of the boundary wall of seminiferous tubules, and lymphocytic infiltration of the interstitium. The reproductive excurrent ducts and prostate appeared morphologically normal except for the presence of focal accumulations of white blood cells in the connective tissue stroma. In the testis many white blood cells were shown to be CD4+, indicating the presence of abundant host cells (T-helper/inducer lymphocytes and macrophages) for HIV-1. Furthermore macrophages and cells of lymphocytic morphology were observed migrating across the boundary walls of hyalinized seminiferous in tubules to enter the lumen. In 9 of the 23 cases tested for HIV-1 protein expression by immunocytochemistry. HIV-1 + cells of lymphocytic/monocytic morphology were found in the seminiferous tubules and interstitium of the testis, epididymal epithelium, and connective tissue of the epididymis and prostate. One patient with epididymal blockage had accumulations of HIV-1-antigen-positive cells of macrophages morphology in the distended lumen of the efferent ducts. There was no evidence of active HIV-1 infection in germ cells or Sertoli cells of the seminiferous tubules or other epithelial cells lining the excurrent ducts or prostatic glands.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Recombinant human granulocyte-macrophage colony-stimulating factor promotes megakaryocyte maturation in nonhuman primates.

Megakaryocytes are responsive to several nonlineage-specific cytokines in vitro. In this study, we examined the in vivo effects of recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) on late stages of megakaryocytopoiesis in the rhesus monkey. Four rhesus monkeys were given 10 micrograms/kg body weight/day of rh GM-CSF s.c. in two divided doses daily for 8 days. Megakaryocyte maturation was evaluated serially by measuring nuclear ploidy and cytoplasmic size. GM-CSF-treated monkeys developed significant shifts in ploidy distribution from days 3 through 15 (p less than or equal to 0.001), with increased frequencies of 64N and 128N megakaryocytes. Mean megakaryocyte size increased 92.5% on day 9, paralleling the increase in DNA content, although megakaryocyte size within ploidy groups did not increase. Megakaryocyte number remained unchanged following rh GM-CSF treatment. The platelet count responses were variable, and mean platelet volume did not change. The present study demonstrates that therapeutic doses of rh GM-CSF stimulate megakaryocyte endomitosis and increase mean size. The data indicate that GM-CSF is effective in promoting the maturation stage of megakaryocyte development but does not result in a consistent thrombopoietic response.

Animals↗
PubMed1991

O2 pressures between 0.12 and 2.5 atm abs, circulatory function, and N2 elimination.

To study the effects of inhaled oxygen pressures on N2 elimination, 72, 2-h washouts were performed in 6 subjects at oxygen pressures of 0.12, 0.2, 1.0, 2.0, and 2.5 atm abs using a closed circuit system that supplied an O2-argon mixture and collected the N2 off-gassed. Hypoxia induced a significant (9.4%, P less than 0.05) increase in nitrogen eliminated as compared to normoxia. Pure oxygen breathing induced a small, insignificant (3.5%) decrease in nitrogen yields, but further increases in oxygen pressure induced significant decreases in nitrogen yields (-8.9% and -16.9% for 2.0 and 2.5 atm abs, respectively). Heart rate, cardiac output, skin perfusion and leg blood flow decreased, whereas mean arterial pressure increased with increasing oxygen pressure. We conclude, therefore, that perfusion-dependent N2 elimination decreases secondary to vasoconstriction induced by increasing oxygen pressures. Changes in inhaled oxygen pressures during different phases of compression-decompression may induce alterations in the rate of inert gas uptake and elimination. Although not currently quantifiable, such alterations would imply added uncertainties in the computation of decompression schedules. Oxygen breathing during decompression should be performed at the lowest possible ambient pressure compatible with freedom from pathogenic bubble formation.

Adult↗
PubMed1991

Tyrosine phosphorylation of GAP and GAP-associated proteins in lymphoid and fibroblast cells expressing lck.

The Ras GTPase activating protein (GAP) is a strong candidate for the protein that links protein-tyrosine kinases to the Ras mitogenic pathway. GAP and two associated proteins, p62 and p190, were shown to be phosphorylated on tyrosine in the LSTRA thymoma cell line, in which the p56lck tyrosine kinase is overexpressed as a result of retroviral promoter insertion. In NIH3T3 fibroblasts expressing specific oncogenic and transformation-defective variants of p56lck, we found that the tyrosine phosphorylation of GAP complexes required both enzymatic activation and myristylation of p56lck, and correlated with lck transforming activity. The interaction between p62 and p190 from lck-transformed fibroblasts and GAP could be reconstituted in vitro using bacterial TrpE fusion proteins containing GAP Src homology 2 (SH2) domains. In vitro complex formation was insensitive to the prior denaturation of SH2 ligands, suggesting that SH2-binding sites are formed by linear peptide sequences. These results suggest that the tyrosine phosphorylation of GAP, and its interactions with SH2-binding proteins, may be involved in fibroblast transformation by activated lck, and may participate in signal transduction and cellular transformation in lymphoid cells.

Animals↗
PubMed1990

Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors.

Phospholipase C gamma 1 (PLC gamma 1) and p21ras guanosine triphosphatase (GTPase) activating protein (GAP) bind to and are phosphorylated by activated growth factor receptors. Both PLC gamma 1 and GAP contain two adjacent copies of the noncatalytic Src homology 2 (SH2) domain. The SH2 domains of PLC gamma 1 synthesized individually in bacteria formed high affinity complexes with the epidermal growth factor (EGF)- or platelet derived growth factor (PDGF)-receptors in cell lysates, and bound synergistically to activated receptors when expressed together as one bacterial protein. In vitro complex formation was dependent on prior growth factor stimulation and was competed by intracellular PLC gamma 1. Similar results were obtained for binding of GAP SH2 domains to the PDGF-receptor. The isolated SH2 domains of other signaling proteins, such as p60src and Crk, also bound activated PDGF-receptors in vitro. SH2 domains, therefore, provide a common mechanism by which enzymatically diverse regulatory proteins can physically associate with the same activated receptors and thereby couple growth factor stimulation to intracellular signal transduction pathways.

ErbB Receptors↗
PubMed1990

Clear cell adenocarcinoma of the lower genital tract. Correlation of mother's recall of diethylstilbestrol history with obstetrical records.

The written obstetric records of maternal exposure to diethylstilbestrol (DES) were used as a criterion standard and compared with the DES exposure history recalled by mothers of women with vaginal, cervical, or indeterminable vaginal/exocervical clear cell adenocarcinoma. Among cervical cases, the sensitivity of maternal recall was 50% (N = 2), and its specificity was 100%. Among vaginal and vaginal/exocervical cases, this sensitivity was 72%; specificity was 60%; and the majority of these mothers who said they did not take DES were DES positive by written records. Thus investigators should avoid using maternal recall alone to measure DES exposure. Among subjects for whom written maternal obstetric records were available, 88% of vaginal cases and 46% of cervical cases were DES positive. The authors conclude that few cases of vaginal clear cell adenocarcinoma should occur in young women as the cohort of women exposed in utero to DES continues to age, whereas cases of cervical origin may continue to occur.

Adenocarcinoma↗