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Biomedical subjects

C Hanson

Publications and source records attributed to C Hanson.

At least 55 records · Page 3Linked to original sources

Detection of RB1 deletions by fluorescence in situ hybridization in malignant hematologic disorders.

We evaluated the usefulness of fluorescence in situ hybridization (FISH) using different-colored commercial RB1 and 13qter DNA probes to identify RB1 deletions in interphase nuclei of bone marrow from 24 patients with agnogenic myeloid metaplasia (AMM), 20 patients with multiple myeloma (MM), 21 patients with other hematologic malignancies, and 25 normal bone marrow transplant (BMT) donors. Based on the 25 normal BMT donors, the upper boundary for the normal percentage of nuclei with one RB1 signal was 6.5%. Based on eight specimens known to have a deletion of 13q14 by cytogenetic studies, the lower limit of abnormal for the percentage of nuclei with one RB1 signal was 12.5%. More than 12.5% of nuclei had a single RB1 signal in 7/24 (29%) patients with AMM and 3/20 (15%) patients with MM. None of the 21 patients with hematologic malignancies other than AMM or MM had more than 12.5% nuclei with loss of RB1. The results of this study suggest that FISH with RB1 probes is useful to detect loss of RB1 in interphase nuclei from patients with hematologic disorders who have chromosome abnormalities involving 13q14. Thus, FISH with probes for RB1 is efficacious to investigate the pathogenesis of RB1 in malignant neoplasms and is a useful adjunct to conventional cytogenetic studies in clinical practice when abnormalities of 13q14 are involved.

Adult↗

Absolute copy number and relative change in determinations of human immunodeficiency virus type 1 RNA in plasma: effect of an external standard on kit comparisons.

Use of a common set of human immunodeficiency virus type 1 (HIV-1) RNA standards eliminated differences among absolute HIV-1 RNA copy number estimates made with three commercially available assays. The relative changes in the viral RNA levels determined by the commercial assays were similar and were unaffected by the use of a common set of standards.

Female↗

Both the polycythemia- and anemia-inducing strains of Friend spleen focus-forming virus induce constitutive activation of the Raf-1/mitogen-activated protein kinase signal transduction pathway.

The erythroleukemia-inducing Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo). In an attempt to understand how the virus causes Epo independence, we have been studying signal transduction pathways activated by Epo to determine if SFFV exerts its biological effects by constitutively activating any of these pathways in the absence of Epo. We previously demonstrated that Stat proteins, the downstream components of the Epo-induced Jak-Stat pathway, are constitutively activated in SFFV-infected cells. In this study, we demonstrate that SFFV also activates Raf-1, MEK and mitogen-activated protein (MAP) kinase, the downstream components of the Raf-1/MAP kinase pathway. This pathway was activated in cells infected with the polycythemia-inducing strain of SFFV, which induces both proliferation and differentiation of erythroid cells in the absence of Epo, as well as in cells infected with the anemia-inducing strain of the virus, which still require Epo for differentiation. Inhibition of Raf-1 by using antisense oligonucleotides led to a partial inhibition of the Epo-independent proliferation of SFFV-infected cells. Expression of the transcription factors c-Jun and JunB, but not c-Fos, was induced in SFFV-infected cells in the absence of Epo, suggesting that constitutive activation of the Raf-1/MAP kinase pathway by the virus may result in deregulation of AP-1 activity. We conclude from our studies that infection of erythroid cells with SFFV leads to the constitutive activation of signal transduction molecules in both the Jak-Stat and Raf-1/MAP kinase pathways and that both of these pathways must be activated to achieve maximum proliferation and differentiation of erythroid cells in the absence of Epo.

Anemia↗

Catecholamines inhibit growth in fetal sheep in the absence of hypoxemia.

To evaluate contributions of catecholamines to inhibition of growth during chronic hypoxemia or severe undernutrition, epinephrine (Epi; 0.25-0.35 microg . kg-1 . min-1) or norepinephrine (NE; 0.5-0.7 microg . kg-1 . min-1) was administered to normoxemic fetuses in twin-pregnant ewes for 8-12 days, from 125 to 127 days of gestation. Both had similar effects and decreased fetal weight by approximately 20% relative to control twins (P < 0.01). Weight gain ceased during infusion of Epi or NE (-21 +/- 14.8 or 14 +/- 20.9 g/day), whereas controls gained 93 +/- 13.2 g/day (P < 0.01). Effects on tissues and organs varied, spleen and thymus being most retarded, whereas brain weight and skeletal measures were affected little. Selected muscles from infused fetuses weighed 72% of those in controls. Growth ceased during infusion (P < 0.001). Weight gain of hindlimb bones was negligible, but length increased at 56% of control rates. Arterial blood CO2 and plasma insulin were decreased (P < 0.001), but plasma glucose, growth hormone, and blood oxygenation increased (P < 0.001). Actions of Epi and NE could underlie asymmetrical growth retardation occurring in many adverse physiological situations during fetal development.

Animals↗

Measurement of the cell proliferation rate of bone marrow erythroid precursors by flow cytometry: initial applications to multiple myeloma.

To investigate the pathophysiology of anemia, a two-color flow cytometric method was developed that measures the proliferative rate of the marrow erythroid cells (EPR). The method uses a monoclonal antibody, RC17.2, to identify erythroid precursors and propidium iodide to determine the %S-phase. This technique was then used to test the hypothesis that a decrease in the proliferative rate of the marrow erythroid precursors contributes to the anemia of multiple myeloma. The EPR was determined on the marrow aspirate from 56 patients and the mean EPR was 31.2% (median, 31: range, 14-55). Patients with anemia (n = 36) had a median EPR of 27% compared to 35% for those patients with a normal Hgb (p = < 0.001); however, there was no difference in the % marrow erythroid precursors (p = 0.96) or % marrow plasma cells (p = 0.08) between the two groups. These results suggest that one possible cause for the anemia of myeloma is a decrease in the EPR. This flow cytometric technique may also be useful in studying other anemias.

Anemia↗

Is paternal mitochondrial DNA transferred to the offspring following intracytoplasmic sperm injection?

During intracytoplasmic sperm injection (ICSI) the whole sperm, including head, midpiece and tail, is injected into the middle area of the oocyte. To find out what happens to the sperm mitochondria after ICSI, we checked the first six children born after ICSI treatment for occurrence of paternal mitochondrial DNA (mtDNA). The difference between maternal and paternal mtDNA in the investigated couples in our study was confined to single-base pair substitutions and we had to rely on restriction enzyme cleavage to differentiate between the mitochondrial genomes of the parents. With this kind of assay we were able to reach a sensitivity of about 0.2% for the paternal mtDNA. However, as uneven partition between tissues of heteroplasmic mtDNA is expected to occur, it would not be unlikely that an enrichment to 0.2% would occur in a given tissue if paternal mtDNA was transmitted by the ICSI procedure. We did not detect this level in the blood in any of the six children.

Adult↗

Clinical aspects on the use of preimplantation genetic diagnosis in couples at risk.

BACKGROUND: Preimplantation genetic diagnosis (PGD) is a new technique which may become an attractive alternative to traditional prenatal diagnosis for couples at risk of getting children with severe genetic diseases. We here report our experience after the first trials in Sweden. METHODS: On day three after fertilization by intracytoplasmic sperm injection (ICSI) one or two blastomeres were biopsied and diagnosed by fluorescence in situ hybridization (FISH). Gender determination was done in two cases where the female in the couples were carrier of a severe X-chromosome bound disease (Wiskott-Aldrich disease or ornithine transcarbamylase deficiency). RESULTS: The first couple got an embryo transfer in each of their two treatment cycles. Two female embryos were transferred in the first cycle and one in the second cycle. The second couple did not get any embryo transfer in their two cycles. No clinical pregnancy occurred. CONCLUSION: With the rapidly improving knowledge about inherited disease and refinement of the IVF techniques, PGD will play an important clinical role in high risk groups within a decade for both mono- and polygenic disorders. Both technical as well as legal and ethical problems have however to be solved before these new techniques can be applied on large scale.

Embryonic Development↗

Outbreak of vertigo in Wyoming: possible role of an enterovirus infection.

An epidemiologic investigation was conducted to characterize and evaluate the possibility of a viral aetiology of an outbreak of acute vertigo in Hot Springs Country, Wyoming, during autumn 1992. Case-finding identified Hot Springs County residents who sought medical attention for new onset vertigo during 1 August, 1992-31 January 1993. Thirty-five case-patients and 61 matched controls were interviewed and serum specimens were obtained during January 1993. Case-patients were more likely than controls to report symptoms (e.g. fatigue, sore throat, fever, diarrhoea) of antecedent acute illness. Case-patients did not have a significantly greater prevalence or mean titre of IgG antibodies to respiratory syncytial virus, parainfluenza viruses, Epstein-Barr virus, and cytomegalovirus than controls. Serologic evidence of recent enterovirus infection (IgM antibodies) was found for 74% of case-patients compared with 54% of controls (P < 0.05), suggesting a possible association between vertigo and enterovirus infection. Future studies are needed to define the role of enteroviruses in innerear diseases.

Adolescent↗

After AIDS clinical trial 076: the changing pattern of zidovudine use during pregnancy, and the subsequent reduction in the vertical transmission of human immunodeficiency virus in a cohort of infected women and their infants. Women and Infants Transmission Study Group.

To determine the impact of the AIDS Clinical Trials Group (ACTG) Protocol 076 results on the subsequent use of zidovudine during pregnancy and the transmission rate of human immunodeficiency virus (HIV) in a cohort of mother-infant pairs (Women and Infants Transmission Study), a retrospective analysis was done. Transmission rates were calculated by simple proportion for infants with at least 6 months of follow-up, stratified by date of birth (n = 453 born on or before 1 March 1994; n = 103 born after 1 March 1994). Transmission rates decreased from 19% to 8% (P = .005, Fisher's exact test). Zidovudine use increased during pregnancy (22% vs. 89%) and in newborns (1% vs. 79%). Both cohorts were similar with respect to maternal immunosuppression, mode of delivery, and demographics. In summary, in a perinatal HIV observational study, the release of results of ACTG Protocol 076 was associated with an increase in zidovudine use during pregnancy and a concomitant decline in HIV transmission from mothers to infants.

Adult↗

Anaemia in housed newborn lambs.

The mean (+/- sd) packed cell volume (PCV) of the lambs in a flock mated by 'out-of-season' breeding methods and housed throughout the last six weeks of pregnancy and the whole of the suckling period declined to 23.3 +/- 3.34 per cent when the lambs were a month old, but recovered spontaneously to reach values within the normal range (30 to 35 per cent) before they were weaned at two months. Clinical signs of anaemia were observed in only a few lambs at three weeks old but the PCV values of all the lambs were significantly lower at this time than at weaning. There was no relationship between the PCV values during the two to four weeks after birth and the growth rate of the lambs. The administration of 200 mg iron, as iron dextran, by intramuscular injection to the newborn lambs prevented the decrease in PCV, but had no measurable effect on the health or growth rate of the lambs throughout the suckling period.

Anemia, Iron-Deficiency↗

Fluorescent in situ hybridization analysis of chromosomally normal gametes and abnormal arrested embryos.

OBJECTIVE: The purpose of the present study was to investigate if the arrested embryos from a couple with several previously failed IVF treatments were chromosomally normal. Probes for chromosomes X, Y and 18 were used. RESULTS: A couple had undergone 7 in vitro fertilization treatments over a 2 1/2-year period without achieving a pregnancy. In each cycle, where fertilization was obtained, the development of the embryos was arrested. Fluorescent in situ hybridization probes for chromosomes X and Y (and 18) was carried out on gametes and on embryos in 2 separate cycles. Sperm and oocytes were normally haploid X0 or Y0. The nuclei of the blastomeres were fragmented and mosaic for X or Y, or monosomic X0, despite the fact that 2 pronuclei had been assessed on day 1 following intracytoplasmic sperm injection. CONCLUSION: Chromosomally normal gametes can result in abnormal embryos manifested by arrested development and unexplained infertility.

Adult↗