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Biomedical subjects

M E Miller

Publications and source records attributed to M E Miller.

At least 217 records · Page 12Linked to original sources
PubMed1982

Extracts of chronic lymphocytic leukemia lymphocytes have a high level of DNA repair activity fo O6-methylguanine.

Extracts of peripheral lymphocytes from six individuals with chronic lymphocytic leukemia (CLL) were assayed for the ability to remove O6-methylguanine (O6MeGua) from exogenous DNA. The O6MeGua-removing activity in CLL lymphocytes, predominantly B cells, was approximately 7-fold higher than in B lymphocytes of normal individuals and about 2-fold higher than in the unstimulated T type cells of normal persons. The activity measured in extracts of lymphocytes from three blood relatives was in the upper range of the normal distribution. Over 80% of the removal of O6MeGua was accomplished by the transfer of the methyl group to cysteine moieties of acceptor proteins in a stoichiometric reaction. If one assumes one acceptor group per acceptor protein, the calculated number of acceptor molecules per CLL lymphocyte falls between 91,000 and 220,000. Thus CLL lymphocytes do not show lower O6MeGua-removing activity, in contrast to many tumor cell strains or transformed cell lines, which are reported to have a deficient methyl excision repair phenotype (Mer-). Instead, the CLL lymphocytes act as if they have a super-Mer+ phenotype.

Blood Proteins↗
PubMed1982

Effects of benzene inhalation on murine pluripotent stem cells.

Effects of benzene inhalation on mouse pluripotent hematopoietic stem cells have been evaluated. Male mice 8--12 wk old were exposed to 400 ppm benzene for 6 h/d, 5 d/wk, for up to 9 1/2 wk. At various time intervals exposed and control animals were killed, and cardiac blood was evaluated for changes in white blood cell (WBC) and red blood cell (RBC) content. In addition, femora and tibiae were evaluated for total marrow cellularity, stem cell content (as measured by the spleen colony technique), and the percent of stem cells in DNA synthesis (as determined by the tritiated thymidine cytocide technique). Exogenous spleen colonies grown from marrow of exposed animals were counted, identified, and scored by histological type. Exposure to benzene caused significant depressions of RBCs and WBCs throughout the exposure period, which continued for at least 14 d after exposure. Bone marrow cellularity and stem cell content were also depressed in exposed animals throughout the study. Tritiated thymidine cytocide of spleen colony-forming cells was generally increased in exposed animals, perhaps indicating a compensatory response to the reduction of circulating cells. Spleen colonies of all types were depressed after exposure to benzene. The significance of the reduction in cellularity, stem cell content, and changes in morphology of spleen colonies is discussed in relation to cellular toxicity and residual injury.

Animals↗
PubMed1982

Plasma levels of immunoreactive erythropoietin after acute blood loss in man.

Plasma levels of immunoreactive erythropoietin (Ep) were measured after acute blood loss (50, 75, 200 and 450 ml) in man in order to determine the volume of blood loss required to trigger an Ep response as well as to define the reticulocyte response. There was a highly significant (P less than 0.01) linear increase in reticulocyte count after 200 and 450 ml of blood loss. Analysis of trends also showed a highly significant (P less than 0.01) linear response of haematocrit and Ep after a 450 ml blood loss. The reticulocyte count increases were not dependent on a prior increase in Ep level indicating that at least two mechanisms are operative in restoring the red cell mass to normal after blood loss.

Adult↗
PubMed1982

Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings.

Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 microliters of sample, the essay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases in circulating Ep levels in physiological and clinical conditions known to be associated with stimulation of suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RIA inthe hematology clinic, which will most certainly be expanded with its more extensive use.

Adolescent↗
PubMed1982

Functional alterations in the membrane of motile polymorphonuclear leukocytes.

We have applied microdocumentary techniques to the study of movement of human PMN's and their behavioral response to a chemoattractant. We discuss here findings which suggest a different interpretation from currently accepted theory. Videotape recordings were made on the movement of human PMN's. A slide modified from previous descriptions was designed to predict a straight-line gradient which could be maintained for periods up to 60 minutes. PMN suspensions were placed on the bridge of the slide with the chemoattractant N-formylmethionylleucyl-phenylalanine (F-Met-Leu-Phe) placed in one wall and PMN suspension medium in the well on the other side of the bridge. Videotapes were traced on the monitor screen at 15-second intervals. A lack of consistent orientation and "head-tail" polarity of any individual PMN was observed. Apparent polarity was observed less than 10% of the time. The net movement of cells in a given field was always toward the direction of the approaching and maintained gradient, but any individual cell failed to show a sustained directional orientation or movement toward the gradient. Individual cells constantly reoriented. Analysis of time-dependent characteristics of the chemotactic response is essential to the ultimate understanding of PMN motility.

Cell Membrane↗
PubMed1982

Isolation of ovine lymphocytes, granulocytes, and monocytes by counterflow centrifugation elutriation.

A simple, brief 1-step counterflow centrifugation elutriation technique is described for the recovery of highly purified populations of lymphocytes and granulocytes from adult and fetal ovine peripheral blood. Monocytes are obtained as an enriched population. Lymphocyte and granulocyte recoveries average 80%, higher than with routine gradient centrifugation procedures. In this described technique, inexpensive medium is used, and it is completed in about 90 minutes. The individual blood cellular populations, when tested appropriately, demonstrated normal functional responses.

Animals↗
PubMed1981

Chemotactic factor-induced effects upon deformability of human polymorphonuclear leukocytes.

We have compared the effects of the synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe), on the deformability and chemotaxis of human polymorphonuclear leukocytes (PMNs). By utilizing the technique of cell elastimetry (deformability), which measures the negative pressure required to aspirate cells into a micropipet, we have shown a correlation between f-Met-Leu-Phe concentrations and PMN deformability which parallels the effects of that chemoattractant on filter chemotaxis. At concentrations as low as 10(-11) M, a change in the deformability characteristics of a population of neutrophils was demonstrated. The increase in deformability became most marked at peptide concentrations in the range of 1-5 x 10(-9) M, corresponding to the optimal concentration range in the filter chemotaxis assay. Concentrations of 10(-8) M and greater were associated with a significant increase in the negative pressure required to aspirate the cells into a micropipet. Alterations in PMN deformability, therefore, occur as a natural consequence of stimulation of a human PMN with a chemotactic factor and may be a prerequisite to efficient movement.

Cell Movement↗
PubMed1981

Compression-related defects from early amnion rupture: evidence for mechanical teratogenesis.

The features of 27 cases of limb/body wall deficiency (formerly termed cyllosomus and pleurosomus) were evaluated and the anomalies were interpreted as being band-related defects and/or compression-related defects. The latter included limb deficiency, body wall deficiency, neural tube defects, scoliosis, postural deformations, growth deficiency, and short umbilical cord. It is hypothesized that the single event of early amnion rupture can explain both the band-related defects and the compression-related defects. Experimental animal studies are in accord with this hypothesis; amnion puncture of rat fetuses during early gestation produces a comparable array of defects. The term amnion rupture sequence is suggested to describe the overall pattern of malformation that results from amnion rupture whether these defects are band related, compression related, or a combination of the two. There is considerable variation in the phenotype of amnion rupture sequence, with limb/body wall deficiency representing the more severe end of the spectrum. It is important to recognize and correctly diagnose amnion rupture sequence because it is usually a sporadic event.

Abdominal Muscles↗
PubMed1981

Clonazepam acetylation in fast and slow acetylators.

Six slow acetylators (SAs) and six rapid acetylators (RAs), as determined by sulfamethazine (SMZ) phenotyping, were each given a 2-mg oral dose of clonazepam. Ninety-six-hour urine collections from these subjects were analyzed for clonazepam, 7-amino clonazepam (7-AM, clonazepam nitroreduced metabolite), and 7-acetamido clonazepam (7-ACT, N-acetylated 7-AM). The SA group excreted more 7-AM and less 7-ACT than the RA group; mean (+/- Sd) recovered as 7-AM was 22.7 +/- 5.0% for the SA group and 13.6 +/- 4.1% for the RA group and mean (+/- SD) recovered as 7-ACT was 1.5 +/- 0.4% for the SA group and 3.9 +/- 1.8% for the RA group. Both differences were substantial (p less than 0.02 by unpaired t test) and indicate that the rate of acetylation of 7-AM to 7-ACT in the biotransformation of clonazepam is determined by the acetylator phenotype.

Acetylation↗
PubMed1981

Murine bone marrow cell line producing colony-stimulating factor.

A cell line (H-1) derived from the adherent layer of a 14-wk-old Dexter bone marrow culture has been maintained as cloned and uncloned lines through 21 passages at the time of these studies. These cell lines develop many fat droplets as they age and become confluent. The uncloned line produces increasing amounts of colony-stimulating activity as the cells become confluent. Feeder layers or supernatants from the nonconfluent or confluent fat-laden cells stimulate the formation of greater numbers of colonies derived from cultures of colony-forming units (CFU) than does medium from L cell culture containing colony-stimulating factor (CSF). Antibody to the CSF-containing medium from L cell culture neutralizes the colony-stimulating activity, thus showing immunologic similarity to a known molecular species that stimulates colony production in a CFU culture that produces granulocyte or macrophage populations, or both.

Adipose Tissue↗
PubMed1981

Immune-inflammatory response in the human neonate.

This review briefly summarizes the salient points regarding the immune inflammatory status of neonatal host defenses. The neonate can marshal an immune response to most antigens and infectious agents. The data from previous studies in this area suggested that neonates were "immunologically null,' but much of this information was derived from interpretations which failed to take into account the inflammatory response. Humoral and cellular deficiencies of cell movement and, perhaps, ingestion and bactericidal activities probably contribute significantly to the compromised host defense characteristic of this period of life. The interactions of these major areas in enabling the neonate to resist infections are largely unknown. The answers to these compelling research questions should provide directions in the future diagnosis and treatment of neonatal septicemia.

Antibody Formation↗
PubMed1981

Diurnal levels of immunoreactive erythropoietin in normal subjects and subjects with chronic lung disease.

Serum levels of immunoreactive erythropoietin (Ep) were measured in 48 normal male and female volunteers, ages 20-60 years, to establish a control value for Ep of 18.5 +/- 5.0 (mean +/- SD) mU/ml. Levels of the hormone were also measured sequentially over a 24 h period of time in an additional 17 'normal' volunteers with no diurnal variation. Diurnal levels of immunoreactive Ep were also measured in 30 subjects, with chronic lung disease. These patients, in contrast to normal subjects exhibited a diurnal variation in the level of immunoreactive Ep with peak levels occurring at midnight. The only variable measured which correlated with the serum immunoreactive Ep level in subjects with chronic lung disease was the level of carboxyhaemoglobin (P less than 0.02).

Adult↗
PubMed1981

Reduced concanavalin A capping of neonatal polymorphonuclear leukocytes (PMNs).

Neonatal polymorphonuclear leukocytes (PMNs) have previously been shown to be chemotactically deficient. To probe the mechanism(s) responsible for this deficiency, we have investigated the phenomenon of concanavalin A-induced capping in neonatal PMNs. PMNs from cord blood of 17 healthy, full-term infants and 17 normal adult volunteers were isolated by standard Ficoll-Hypaque and dextran sedimentation. After incubation with and without colchicine, the cells were reincubated with fluorescein isothiocyanate-Con A, fixed, and prepared in wet mounts. Using a fluorescence microscope, PMNs were identified, and percentage of the capped cells was counted. Upon treatment with colchicine, adult PMNs showed a significant increase in the percentage of capped cells. By contrast, the cord blood PMNs showed no significant increase in capping after colchicine treatment. The difference between percentage of PMNs showing colchicine-induced capping in adult and cord blood was highly significant (P less than 0.01; Student's t test).

Adult↗