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Biomedical subjects

C Andrews

Publications and source records attributed to C Andrews.

At least 109 records · Page 6Linked to original sources

Transcription termination factor rho mediates simultaneous release of RNA transcripts and DNA template from complexes with Escherichia coli RNA polymerase.

Dissociation of RNA and DNA from Escherichia coli RNA polymerase in transcription complexes prepared with enzyme molecules located within and near a rho-dependent transcription termination region on bacteriophage T7 D111 DNA has been studied using a membrane filter-binding assay. Rho protein with ATP present mediated rapid (half-time approximately 27 s) simultaneous dissociation of about 50% of both RNA and DNA. RNA molecules were preferentially released from enzyme molecules located within the termination region. Rapid release of RNA and DNA depended on a nucleoside triphosphate but did not depend on sigma factor. Pretreatment of complexes with ribonuclease prevented dissociation of DNA. Nearly simultaneous dissociation of both RNA and DNA was also detected after a lag of 3 min when the isolated transcription complexes were incubated with all four ribonucleoside triphosphates in the absence of rho factor. In this case, release presumably occurred at the rho-independent termination site that is 5990 nucleotides downstream from the A1 promoter. Thus, the dissociation of DNA from RNA polymerase at rho-dependent and rho-independent transcription termination sites is coupled with or occurs spontaneously soon after the release of transcripts at both sites.

DNA, Viral↗

Total skin electron beam and total nodal irradiation for treatment of patients with cutaneous T-cell lymphoma.

Sixteen patients with advanced cutaneous T-cell lymphoma (CTCL) with or without lymph node involvement, but without evidence of extranodal manifestations, were treated with a combination of total skin electron beam therapy (TSEB) and total nodal irradiation (TNI). Fourteen (87%) patients achieved a complete response (CR) lasting from 1 to 84+ months (median, 8+ months) from the completion of treatment. The best results occurred in 6 patients with pretumorous intracutaneous CTCL (Stages IB and IIA) where the CR has lasted in all patients from 8 to 84+ months (median about 27+ months). Conversely, a long-term CR occurred in only one of five patients with tumor-phase intracutaneous CTCL (Stage IIB) and in none of the 5 patients with histopathologically proven nodal involvement (Stage IVA). Radiotherapy was well tolerated with the major toxicity being bone marrow suppression. We conclude that combined TSEB and TNI is a relatively safe and effective treatment for patients with CTCL prior to the development of lymph node involvement. Long-term follow-up is needed to assess the curative potential of this treatment.

Adult↗

Dipeptidylaminopeptidase IV (DAP IV) in B- and T-cell leukaemias.

A cytochemical study in samples from 100 lymphoid leukaemias, 84 of B-cell type and 16 of T-cell type, was carried out with three acid hydrolases: DAP IV, acid phosphatase (AP) and alpha-naphthyl acetate esterase (ANAE). DAP IV was studied in leukaemic T-cells both by cytochemistry and by a monoclonal antibody with the immunoperoxidase technique. Both methods showed similar results. AP and ANAE gave weak reactions in immature B-cell leukaemias (common-ALL and B-CLL) and were strongly expressed in plasma cell disorders. DAP IV showed no activity in any of the types of B-cell leukaemia studied and was strongly positive in some T-cell leukaemias but with a more restricted distribution than ANAE and AP. T-lymphoblasts (T-ALL) and mature (T8+) leukaemias were DAP IV negative. Within the T4+ malignancies DAP IV was positive in four T-prolymphocytic leukaemias, one of two T-CLL and one of three Sezary syndrome cases. Although DAP IV is strictly T-cell specific it does not appear to aid the differentiation between B- and T-cell disorders or the identification of T-cell subsets as determined by monoclonal antibodies. It remains to be established whether this enzyme will define a functionally distinct T-cell subset.

Acid Phosphatase↗

Intracytoplasmic inclusions in B prolymphocytic leukaemia: ultrastructural, cytochemical, and immunological studies.

The intracytoplasmic inclusions seen in most cells from a patient with B prolymphocytic leukaemia were analysed using both light and electron microscopy. They consisted of a dense homogeneous structure and were surrounded by a membrane, which had no continuity with the Golgi cisternae or the endoplasmic reticulum; some inclusions had a clear association with small lysosomal granules. Immunofluorescence and immunoperoxidase studies using light microscopy failed to elucidate completely the nature of the inclusions, but immunocytochemical reactions performed using electron microscopy suggested an immunoglobulin nature. All inclusions were negative for acid phosphatase and periodic acid Schiff. The nature of the inclusions described in the prolymphocytes of this patient were compared with those previously recorded in B prolymphocytic leukaemia.

Aged↗

The effect of vitamin D3 metabolites on normal and leukemic bone marrow cells in vitro.

We studied the effects of 1,25-dihydroxyvitamin D3 and other metabolites of vitamin D3 on the maturation in liquid culture and on colony formation in semisolid media of marrow and buffy coat cells from patients with myeloid leukemias and from normal individuals. After incubation with 1,25-dihydroxy-vitamin D3, a proportion of both normal and leukemic myeloid cells resembled cells of the monocyte-macrophage lineage; these cells expressed alpha-naphthylacetate esterase and were able to phagocytize and kill candida organisms. When granulocyte-macrophage progenitor cells (CFU-GM) were incubated with 1,25-dihydroxyvitamin D3, the number of monocyte-macrophage colonies was increased and the number of granulocyte colonies was reduced; megakaryocyte colony formation (CFU-Mk) was inhibited substantially; and there was no effect on erythroid (BFU-E) or multilineage (CFU-GEMM) progenitor cell colony formation. We propose that 1,25-dihydroxyvitamin D3 may induce cells that are normally committed to differentiate along the granulocytic pathways to differentiate instead along the monocyte-macrophage pathway. If these in vitro observations reflect the in vivo activity of 1,25-dihydroxyvitamin D3, it may be involved in the modulation of collagen deposits in the bone marrow.

24,25-Dihydroxyvitamin D 3↗

Dipeptidylaminopeptidase IV activity in normal and leukemic T-cell subpopulations.

Dipeptidylaminopeptidase IV (DAP IV) cytochemical reactivity was investigated in monoclonal antibody defined T-lymphocyte subpopulations from normal blood and in cells from a series of T-cell leukemias of defined immunologic phenotype. A combined monoclonal antibody/immunocolloidal gold technic, which enabled simultaneous visualisation of immunogold label and DAP IV reactivity, was used to study enzyme reactivity in normal T-cell subpopulations. Single or several discrete granules of DAP IV reaction product were observed in 72% of OKT3+ and OKT4+ cells, whereas a significantly (P less than 0.01) lower percentage of OKT8+ cells (41%) displayed positivity; B-cells were invariably DAP IV negative. In the T-cell leukemias, DAP IV reactivity was strongest in T-lymphoblastic lymphoma and T-prolymphocytic leukemia cells. In contrast, DAP IV activity was absent or expressed in a minority of cells of the more immature T-acute lymphoblastic leukemia. The enzyme reaction also was negative in lymphocytes from other mature T-cell leukemias: T-chronic lymphocytic leukemia (OKT8+), adult T-cell lymphoma-leukemia, and Sezary syndrome (both OKT4+). DAP IV expression did not parallel that of acid phosphatase or alpha-naphthyl acetate esterase in leukemic T-lymphoid cells except in T-lymphoblastic lymphoma and T-prolymphocytic leukemia, where a strong reaction with the three hydrolytic enzymes was observed.

Antibodies, Monoclonal↗

"Pseudo-endless loop" tachycardia in an AV universal (DDD) pacemaker.

A 3-beat episode of ventricular arrhythmia was recorded in a patient with an AV universal (DDD) pacemaker. This arrhythmia mimicked "endless loop" tachycardia (ELT) because it appeared following a ventricular premature contraction (VPC), its rate approached the preset upper-rate limit and the regular P waves disappeared during the episode. However, as retrograde conduction was absent ELT could not exist. The mechanism of this arrhythmia was based on a combination of interference by VPC of the regular sequence of QRS complexes produced by P wave and the pacemaker commitment to maintain an upper rate limit by prolongation of the programmed pacemaker AV delay.

Electrocardiography↗

Age-related response to two Haemophilus influenzae type b vaccines.

Two types of Hib vaccines were compared for efficacy and safety in 71 normal children in three age groups: 36 to 72 months, 15 to 18 months, and 6 to 8 months. One vaccine contained the Hib-specific capsular polysaccharide, PRP; the second vaccine contained PRP combined with pertussis vaccine, PRP-P. A third vaccine, DTP, was administered to a control group for each age. Anti-PRP antibody levels were greater after vaccination with PRP-P than after PRP in all three age groups. Immunoresponsiveness to both vaccines increased with age. A lower incidence of side effects was seen with both PRP (15%) and PRP-P (20%) than with DTP (56%). The results suggest that PRP-P is both well tolerated clinically and has greater immunogenicity than PRP.

Age Factors↗

BK papovavirus infections in renal transplant recipients: contribution of donor kidneys.

Infections due to BK papovavirus frequently occur in renal transplant recipients [2] and may be involved in a variety of syndromes, including ureteral obstruction, deterioration of graft function, and pancreatic disease. The source of the BK papovavirus in these cases is not clear. Because the renal allograft has been implicated as a source of primary cytomegalovirus infections in renal transplant recipients [3], we investigated the possibility that donor kidneys may also contribute to the transmission of BK papovavirus. A fourfold or greater increase in titers of HAI antibodies to BK papovavirus was observed in 55 (24%) of 230 renal transplant recipients. Seronegative recipients who received kidneys from seropositive donors were 3.5 times more likely to develop an infection due to BK papovavirus than were seronegative recipients of kidneys from seronegative donors. The antibody status of the donor did not affect the likelihood of an increase in titers of antibody to BK papovavirus in seropositive recipients. These results suggest that BK papovavirus may be transmitted with transplanted kidneys and that transplant recipients who are at risk for primary infection by this route are more than twice as likely to have increased titers of antibody to BK papovavirus as those who are at risk for the reactivation of an infection. Further studies should be performed to define the relative role of cadaver vs. living, related kidney donors in the transmission of BK papovavirus and the clinical syndromes that are related to primary and reactivated infections.

Humans↗

Effects of endotoxin tolerance on the hemodynamic changes associated with glycerol administration.

Rats made tolerant to endotoxin are partially protected from the histologic and functional injury that usually accompanies intramuscular administration of glycerol. Glycerol nephrotoxicity appears to correlate with the reductions in renal blood flow and cardiac output which follow injection. Studies were undertaken to determine if endotoxin tolerance would alter these hemodynamic abnormalities. A radiolabelled microsphere technique was employed to measure cardiac output and regional blood flow. Endotoxin-tolerant rats had higher cardiac outputs and renal blood flows and lower renovascular resistances than control rats when studied 90 min after intramuscular glycerol. These observations may partially explain the reduced nephrotoxicity of glycerol in rats made tolerant to endotoxin.

Animals↗

Cytological evidence of transcription of highly repeated DNA sequences during the lampbrush stage in Triturus cristatus carnifex.

Highly repeated, or satellite, DNA fractions have been isolated from total Triturus cristatus carnifex DNA by renaturation kinetics, caesium salt centrifugation and restriction endonuclease digestion. We have shown by DNA/DNA in situ hybridisation and autoradiography that all of these probes bind to C-band positive regions on mitotic or lampbrush chromosomes of T.c. carnifex. Under conditions of DNA to RNA-transcript in situ hybridisation labelled satellite DNA binds to nascent RNA transcripts that are still associated with the DNA axes of many lampbrush loops. The majority of the loops that label heavily in these experiments are located on the long arms of chromosome I, a region previously shown to be rich in highly repeated DNA and to have many of the properties of heterochromatin. These satellite DNA probes also label many loops on a comparable chromosome region in T. marmoratus, a species closely related to T. cristatus. However, in DNA/RNA-transcript hybrids to other more distantly related species of Triturus, there are no chromosome regions that have the same concentration of labelled loop pairs as the long arms of T.c. carnifex and T. marmoratus, although some loop pairs do label. We have cloned two satellite sequences in pBR322, and have obtained the same results using these pure probes as we obtained using satellite probes isolated by other techniques. These results demonstrate unequivocally that satellite DNA is transcribed on lampbrush chromosomes during oogenesis in crested newts.

Animals↗

Maternal holding preferences: a consequence of newborn head-turning response.

Salk observed that in an overwhelming majority of cases (80%) mothers prefer to hold their infants across the left shoulder. This preference occurs over a diversity of cultures and is not related to the hand preference of the mother. Salk suggested a fetal imprinting to the sound of the heartbeat as the mechanism responsible for this phenomenon. While such speculation is intriguing, it is not scientifically testable. 2 experiments were performed to examine a more testable hypothesis. Results of these studies suggest that the initial head-turning preference of an infant is related to the holding preference of its mother.

Age Factors↗

Do patients really want cheap lenses?

There is a strong possibility that many patients perceive newspaper advertisements as a sign of dependability or prestige rather than the evidence of unethical behavior that professionals traditionally frown upon. "Confidence in the doctor" was the foremost reason given for seeking professional service in a survey by a major commercial optical corporation. Two hundred fifty patients interviewed in a contact lens practice agreed, and the tabulated results would indicate that price alone is not a major factor.

Advertising↗

Interspecific "common" repetitive DNA sequences in salamanders of the genus Plethodon.

Intermediate repetitive sequences of Plethodon cinereus which comprised about 30% of the genomic DNA were isolated and iodinated with 125I. About 5% of the 125I-repetitive fraction hybridized with a large excess of DNA from P. dunni at Cot 20. About half of the 125I-DNA in the hybrids was resistant to extensive digestion with S-1 nuclease. The average molecular size of the S-1 nuclease-resistant fraction was about 100 nucleotide pairs. The melting temperature of the S-1 nuclease-resistant fraction was about 2 degrees lower than that of the corresponding fraction made with P. cinereus DNA. These results are taken to indicate the presence in the genomes of P. cinereus and P. dunni of evolutionarily stable "common" repetitive sequences. The average frequency of repetition of the common repetitive sequences is about 6,000 X in both species. The common repetitive fraction is also present in the genomes of other species of Plethodon, although the general populations of intermediate repetitive sequences are markedly different from one species to another. The cinereus--dunni common repetitive sequences could not be detected in plethodontids belonging to different tribes, nor in more distantly related amphibians. The profiles of binding of the common repetitive sequences to CsCl or CS2SO4-Ag+ density gradient fractions of P. dunni DNA suggested that these sequences consisted of heterogeneous components with respect to base compositions, and that they did not include large amounts of the genes for ribosomal RNA, 5S RNA, 4S RNA, or histone messenger RNA. In situ hybridization of the 3H-labelled intermediate repetitive sequences of P. cinereus to male meiotic chromosomes of the same species gave autoradiographs after an exposure of seven days showing all 14 chromosomes labelled. The pattern of labelling appeared not to be random, but was impossible to analyse on account of the irregular shapes and different degrees of stretching of diplotene and prometaphase chromosomes. In situ hybridization of the same sequences to meiotic chromosomes from P. dunni gave autoradiographs after 60 d exposure in which all chromosomes were labelled. These heterologous in situ hybrids can only have involved the "common" repetitive sequences.

Amphibians↗