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Biomedical subjects

D A Miller

Publications and source records attributed to D A Miller.

At least 181 records · Page 10Linked to original sources
PubMed1985

Sequential cardiopulmonary changes after oleic-acid injury in dogs.

Oleic acid (OA) administered to experimental animals increases pulmonary vascular permeability and produces a condition that pathophysiologically resembles adult respiratory distress syndrome (ARDS) in humans. The present study examined the sequence of cardiorespiratory changes after OA infusion and their similarity to ARDS. After a baseline period, mechanically ventilated and anesthetized dogs were administered 0.18 ml/kg body weight OA into the pulmonary artery while hemodynamic and respiratory changes were monitored. After OA infusion, cardiac output fell by 39%, paralleling a 26% decrease in heart rate. Pulmonary vascular resistance (PVR) increased over 200% without a change in pulmonary capillary wedge pressure and initially without an increase in pulmonary artery pressure (PAP). Within 30 min after OA infusion, dynamic pulmonary compliance (Cdyn) was reduced 32% from baseline values, with a coincident increase in the alveolar-arterial PO2 gradient (P[A-a]O2) but without a significant change in the pulmonary shunt fraction (Qsp/Qt). This was followed in 30 min by a further 27% decrease in Cdyn, with a Qsp/Qt in excess of 50%. Both the hematocrit and hemoglobin concentration increased progressively after OA infusion, without a change in plasma protein concentration. The results suggest that the sequence of cardiopulmonary changes after OA injury are initially marked by a decrease in Cdyn and an increase in PVR and P(A-a)O2. This is followed by an increase in Qsp/Qt, PAP, hemoglobin concentration and PCO2. The changes appear related to progressive flooding of the alveolar air space with edema fluid. These findings parallel the sequential cardiorespiratory changes reported to occur in ARDS.

Animals↗
PubMed1985

Transcription of mouse rDNA and associated formation of the nucleolus organizer region after gene transfer and amplification in Chinese hamster cells.

Mouse rDNA can initiate transcription by using only Chinese hamster cell components, and this is associated with nucleolus organizer activity. To demonstrate this, we transferred a 3.2-kilobase segment of mouse rDNA containing the promoter, the transcription initiation site, and part of the external transcribed spacer to dihydrofolate reductase-deficient Chinese hamster cells by cotransformation with an abbreviated mouse dhfr gene. Stepwise selection for methotrexate resistance produced sublines in which the mouse rDNA was usually coamplified with the donor dhfr DNA and occupied the same site or sites in the hamster genome, as shown by in situ hybridization. Transcription from mouse rDNA was demonstrated in two such lines, and S1 protection mapping indicated faithful initiation of the transcript. In some cells from both lines, the chromosome segments containing amplified mouse rDNA showed multiple silver-staining regions (i.e., active nucleolus organizers). Although the transferred mouse rDNA was able to use the rDNA transcriptional machinery of the Chinese hamster, the level of transcription was much lower than expected from the rDNA copy number, and a large fraction of each amplified region showed no silver staining. Since the absence of silver staining is generally correlated with the absence of transcription, many copies of the amplified mouse rDNA may have been in a chromatin conformation in which they could not be transcribed. This was not associated with the extensive methylation seen in other amplified, inactive rDNA sequences.

Animals↗
PubMed1984

Restriction enzyme banding of mouse metaphase chromosomes.

Fixed metaphase chromosomes from mouse strain RIII embryos or A9 cells were treated with a restriction endonuclease, followed by Giemsa staining. Alu I, Hinf I, or Mbo I treatment produced a C-band pattern, and Eco RII or Hae III produced a G-band plus C-band pattern. Ava II and Bst NI each produced a G-band pattern, but on most chromosomes only a small segment of each C-band, adjacent to the centromere, was stained. These tiny residual C-bands may contain a minor satellite located adjacent to the major satellite clusters.

Animals↗
PubMed1984

Mechanism of endonuclease banding of chromosomes.

The restriction endonuclease BstNI markedly reduced the extent of Giemsa staining of the C-band regions of methanol/acetic acid-fixed mouse chromosomes air-dried onto glass slides. The enzyme reduced the amount of hybridizable satellite DNA correspondingly, indicating that its effects can be attributed to cutting satellite DNA into fragments short enough to be removed from fixed chromosomes.

Animals↗
PubMed1984

Busulfan versus cyclophosphamide treatment in the early and late stages of granulocytic leukemia in guinea pigs.

A transplantable granulocytic leukemia (GL-13-BC) in strain 13 guinea pigs, which has many similarities to human CML, was used to test the antineoplastic effects of two alkylating agents, busulfan and cyclophosphamide, administered in the late and early stages of the disease. Busulfan had a pronounced cytoreductive effect on circulating leukemic cells in the late, pre-blast crisis stage of this disease but all treated animals, succumbed to the leukemia with only a marginal increase in survival time relative to that of untreated controls. In this respect the guinea pig model resembles human CML. Survival time was moderately increased with early busulfan treatment but, as in the late treatment group, all animals succumbed to the leukemia. A pronounced cytoreductive action on leukemic cells was also observed in guinea pigs treated with cyclophosphamide. Late treatment with this drug produced highly variable effects on the survival time of leukemic guinea pigs; of the nine animals treated, no effect was observe in five, three showed a significant increase in survival time and one animal was still in remission without treatment when the experiment was concluded. Early treatment with cyclophosphamide produced the most striking finding of this study. Two treatments with this drug produced a complete remission in all of the treated guinea pigs. This remission lasted without further treatment for the duration of the study (greater than 200 days) while all untreated controls died within 27-37 days after receiving leukemic cell transplants. The relevance of these findings to the treatment of human CML is discussed.

Animals↗
PubMed1984

Lymphocyte subpopulations in rat lungs and Peyer's patches.

The distribution of lymphocyte subpopulations in rat lungs and Peyer's patches was examined by immunofluorescent microscopy of frozen sections and single cell suspensions. The results showed that there are differences in the lymphocyte subpopulations in these tissues. More B cells were present in Peyer's patches (56.5%) than in lung (15.2%), and, conversely, there were more T cells (W3/13+) in lung (61.7%) than in Peyer's patches (20.7%). In addition, the great majority of T cells found in Peyer's patches were W3/25+ cells (the phenotypic marker of helper T cells in the rat). This was not the case in lung, where a maximum of 46% of T cells were W3/25+. Alveolar macrophages (defined by adherence to plastic and nonspecific esterase activity) did not express W3/13 or W3/25 antigens.

Animals↗
PubMed1984

Ro 22-3747: a new antiallergic agent for the treatment of immediate hypersensitivity diseases.

Ro 22-3747 was orally active in two animal models of immediate hypersensitivity diseases mediated by immunoglobulin E: the rat passive cutaneous anaphylaxis test (ID50 of 0.65 mg/kg) and a model in which anaphylactic bronchospasm was studied in passively sensitized rats (ID50 of 0.022 mg/kg). In the latter model system Ro 22-3747 was also found efficacious by the aerosol route (Ro 22-3747 was 23-fold more potent than disodium cromoglycate by this route of administration). Like disodium cromoglycate (cromoglycate), Ro 22-3747 appears to act in these in vivo models by inhibition of allergic mediator release because it was a potent inhibitor of antigen-induced histamine release from passively sensitized rat peritoneal cells in vitro (IC50 values of 0.25 and 1.5 microM for Ro 22-3747 and cromoglycate, respectively) and did not exhibit end organ antagonism to histamine, serotonin or slow reacting substance of anaphylaxis. The mechanism by which Ro 22-3747 inhibits mediator release does not appear to involve inhibition of delta 5-lipoxygenase, phospholipase A2 or thromboxane synthase. Cromoglycate and Ro 22-3747 appear to have some similarities with regard to their mechanism of action, as they both exhibit a time-dependent loss of inhibitory activity when preincubated with peritoneal cells in vitro before antigen challenge. In addition, pretreatment with one prevented the subsequent inhibition of histamine release by the other. Unlike cromoglycate, however, Ro 22-3747 (10(-5) to 10(-3) M) also inhibited the release of histamine (3-59%), slow reacting substance of anaphylaxis (12-49%) and thromboxane (0-55%) from antigen-challenged (immunoglobulin G1-mediated) guinea-pig lung fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1984

Computerized attendance surveillance to reduce absenteeism.

Computerized data on absenteeism were used as a basis for employee counseling and disciplinary action, and the effect of this program on absenteeism was assessed. In the pharmacy department of an 1100-bed tertiary-care hospital, a microcomputer program provides weekly print-outs of number of occurrences of absence, reason for absence, and total hours absent for each employee. When an employee is within 10 absent hours or one occurrence of exceeding departmental absenteeism standards, these data are used in informal counseling. If absenteeism standards are exceeded, oral or written warning is given within one week after the violation. Absenteeism among pharmacists and technicians was compared for a 90-day period after implementation of this program and the same period during the year before implementation. The computerized attendance-surveillance program was associated with decreases in the mean number of absence occurrences for both pharmacists and technicians, fewer warnings issued to each group, and an increase in the mean number of hours worked.

Absenteeism↗
PubMed1983

The biological activity of rat intestinal retinoic acid metabolites in the vaginal smear assay.

Vitamin A-deficient rats were given a single intrajugular injection of 1 mg all-trans-[11-3H]retinoic acid and 3 h later the rats were killed. The small intestines were extracted and chromatographed by high-performance liquid chromatography to yield distinct metabolites. These were quantitated using the assumption that the specific activity of the metabolite is equal to that of the parent [3H]retinoic acid. The biological activity of all discernible metabolites was determined in the vitamin A-deficient female rat by vaginal smear assay. Retinoic acid and retinoyl-beta-glucuronide from the preparation had equal activity while no activity was found for any of the other metabolite fractions. Thus, no evidence for an unknown metabolite having potent epithelial differentiating activity could be found in this target tissue of vitamin A action.

Animals↗
PubMed1983

Chromosome localization of highly repetitive human DNA's and amplified ribosomal DNA with restriction enzymes.

Restriction endonucleases cut and partially removed DNA throughout fixed air-dried human metaphase chromosomes. Some enzymes produced a G-banding pattern; some revealed the presence of multiple chromosome-specific classes of highly repetitive DNA in C-band heterochromatin. Enzymes that produced the informative C-band patterns had recognition sequences that were four or five, but not six, base pairs long and did not contain a cytosine-guanine doublet. In both rat and human chromosomes, regions containing amplified ribosomal RNA genes were specifically removed by the restriction endonuclease Msp I.

Chromosome Banding↗
PubMed1983

Decreased glycolipid antigen expression in lymphoma cell variants escaping from anti-glycolipid serotherapy.

Mice challenged with L5178Y lymphoma cells expression high levels of the glycolipid asialo GM2 (gangliotriosylceramide) were protected from tumor growth by passive administration of a monoclonal antibody specific for the glycolipid; in a few antibody-treated mice, ascites cells eventually proliferated which contained a reduced chemical quantity of the glycolipid antigen (3). We now report that the cells emerging from antibody-treated mice had abnormal marker chromosomes identical to those in the cells used for challenge, indicating that the emergent cells were progeny of the challenge inoculum. Flow cytometric analysis revealed that asialo GM2 was undetectable on the surface of greater than 95% of the tumor cells from antibody-treated mice, whereas surface display of H-2 determinants was unchanged from that of the cells used for challenge. Tumor cells arising in challenged but untreated mice consisted of a mixture of asialo GM2-positive and -negative cells, indicating the presence of selective pressures in these mice as well. None of the cells taken from tumor bearing mice differed significantly from the challenge cells in their susceptibility to natural killer cell attack, suggesting that resistance to natural killer cell lysis was not responsible for the proliferation of these cells in vivo. When cells derived from an antibody-treated mouse were used to challenge mice, serotherapy with anti-asialo GM2 had no effect on mouse survival. These results suggest that serotherapy may complement a host anti-tumor response, from which only asialo GM2 deficient cells can escape.

Animals↗
PubMed1982

Studies on the long term effects of SK&F 29661 upon adrenal catecholamines.

SK&F 29661 (1,2,3,4-tetrahydro-7-isoquinoline-sulfonamide) is a potent and selective in vitro and in vivo inhibitor of adrenal phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28). Its Ki value for in vitro inhibition of rat adrenal PNMT was 133 nM. In vivo, the adrenal conversion of 3H-norepinephrine to 3H-epinephrine was maximally inhibited by a single oral dose of 100 mg/kg. In long term chronic studies in rats, adrenal epinephrine was reduced by SK&F 29661 in a dose dependent fashion to greater than 90%, without substantial increases in norepinephrine. Urinary excretion of epinephrine was significantly reduced by the drug both basally and following 2-deoxy-D-glucose stimulation. No drug related changes were found in plasma corticosterone values and only small effects were observed on adrenal tyrosine hydroxylase and PNMT enzyme levels. The cardiac norepinephrine pool and its turnover time were both significantly reduced; its turnover rate, however, was only slightly increased. Our studies indicate that SK&F 29661 is a highly effective, non-toxic and novel pharmacological tool which is useful in depleting adrenal epinephrine stores via inhibition of its biosynthesis.

Adrenal Glands↗
PubMed1982

Blast crisis associated with granulocytic leukemia in strain 13 guinea pigs.

A transplantable granulocytic leukemia (GL-13) in inbred strain 13 guinea pigs had been shown previously to have many characteristics in common with human CML except that a blast crisis did not occur in the terminal stage of the disease. We report here that, after the 25th transplant generation, leukemic guinea pigs began to develop a blast crisis similar to that seen in human CML. This feature of the disease is still present after 90 transplant generations. The transplantation conditions necessary to produce the leukemia (now referred to as GL-13-BC) with a predictable clinical and hematological course over a short interval are described. Thus, s.c. injection of 3.0 X 10(6) leukemic cells results in a slowly rising leukocyte count, due mainly to increasing numbers of myelocytes and mature granulocytes, at about 3 weeks after injection. At this early stage the spleen weights of the leukemic animals are about seven times greater than those of normal controls. Approximately 4-7 days later the leukocyte count rises sharply due to a blast crisis and the animals die shortly thereafter with a mean survival time of 30 (range 25-32) days. It is proposed that the GL-13-BC leukemia could serve as a useful model for investigating the problem of blast crisis associated with human CML.

Animals↗
PubMed1982

Is DNA methylation responsible for mammalian X chromosome inactivation?

MOHANDAS et al. (1981) have proposed that mammalian X chromosome inactivation involves segmental methylation of cytosine residues in the DNA at multiple sites along the X chromosome. Using antibodies specific for 5-methylcytosine, we have found no detectable difference in the extent of methylation of the DNA in the two X chromosomes of owl monkey or human females. Thus inactivation (facultative heterochromatization) of the X chromosome is not due to, or associated with, intense DNA methylation comparable to that seen in most constitutive heterochromatin.

5-Methylcytosine↗
PubMed1982

Analysis of T-cell differentiation antigens in acute lymphatic leukemia using monoclonal antibodies.

Leukemic cells in 134 patients with ALL were analyzed by a panel of mouse monoclonal antibodies. Two antibodies are reactive with all peripheral blood T cells but define different surface antigens (Leu-1 and Leu-4). Two other antibodies react with antigens that are restricted to suppressor/cytotoxic T cells (Leu-2) and to helper T cells (Leu-3). We also used antibodies to the receptor for sheep red blood cells (SRBC) (Leu-5) and to a human "TL-like" antigen that is found on most thymocytes but not in peripheral T cells (Leu-6). An antibody to the human p29.34 "Ia-like" molecule was also tested. Of the 134 ALL patients, 17 had a predominance of SRBC-rosetting (Leu-5+) lymphoblasts ("T" ALL), expressing different surface phenotypes defined by this panel of monoclonal antibodies. These phenotypes were not readily classifiable according to a scheme of sequential stages of normal differentiation proposed. Moreover, the lymphoblasts in 8 of 113 patients not expressing conventional B- to T-cell markers ("null" ALL) reacted with the monoclonal anti-T-cell antibodies. This study suggests that the classification of lymphoblasts in ALL based on the reactivities observed with this panel of mouse monoclonal antibodies is not easily reconciled with current models of normal T-cell differentiation. However, it should be emphasized that the precise sequence of antigenic expression by cells undergoing thymic differentiation is still not fully known, and further phenotypic analysis of ALL cells might contribute to an improved understanding of this malignancy.

Adolescent↗