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Biomedical subjects

A M Miller

Publications and source records attributed to A M Miller.

At least 55 records · Page 3Linked to original sources

Recombination walking: genetic selection of clones from pooled libraries of yeast artificial chromosomes by homologous recombination.

Recombination walking is based on the genetic selection of specific human clones from a yeast artificial chromosome (YAC) library by homologous recombination. The desired clone is selected from a pooled (unordered) YAC library, eliminating labor-intensive steps typically used in organizing and maintaining ordered YAC libraries. Recombination walking represents an efficient approach to library screening and is well suited for chromosome-walking approaches to the isolation of genes associated with common diseases.

Animals↗

Dietary fish oil supplementation alters LTB4:LTB5 ratios but does not affect the expression of acute graft versus host disease in mice.

One of the mechanisms by which corticosteroids may modify acute graft vs host disease (GvHD) is via inhibition of arachidonic acid (AA) metabolism. Leukotriene B4 (LTB4) is a product of that pathway which may take part in the pathogenesis of GvHD through the stimulation of T-lymphopoiesis and T-lymphocyte activation. LTB4 is a metabolite of AA (20:4n-6). Alternate dietary sources of polyunsaturated fatty acids (PUFA), specifically eicosapenteinoic acid (20:5n-3) (EPA) and docosahexaenoic acid (22:6n-3) (DHA), shift the LTs formed with a decrease in LTB4 an increase in LTB5. LTB5 is a less potent agonist than LTB4 and this results in a theoretical decrease of LTB4 mediated events. Supplementation of in vitro bone marrow cultures with EPA or DHA had no detrimental effect on myeloid colony formation. Dietary EPA/DHA supplementation in mice with induced GvHD appeared to be safe and well tolerated. The LTB4:LTB5 ratio shifted from 7.65 +/- 1.75 in control-fed animals to 1.03 +/- 0.18. Fish-oil-supplementation did not compromise engraftment or stem cell content. Alone, this therapy was unable to modify GvHD.

Animals↗

Effect of low intravaginal doses of prostaglandin E2 on the closure time of the ductus arteriosus in term newborn infants.

Seventeen term newborn infants (control subjects) and 17 whose mothers had been given intravaginal doses of prostaglandin E2 (PGE2) were examined serially by color Doppler echocardiography to determine whether maternal PGE2 prolonged ductal patency. No clinically relevant differences in closure times were found. Low-dose intravaginal PGE2 therapy was not associated with prolonged ductal patency in term infants.

Administration, Intravaginal↗

Health care reform: clarifying the concepts.

Despite agreement about problems with the health care system, there is disagreement about the remedy. Like most health care reform debates, this article focuses on financing methods rather than service delivery. Reform strategies are intentionally oversimplified into four categories: employer-based or "play or pay"; single-payer and modifications, such as expanding Medicaid or Medicare; market competition; and managed competition, which appears to be favored by the Clinton administration. Cost-control mechanisms and insurance reforms are applicable to all four financing methods. Reform is inevitable. The challenge for nurses is to understand reform issues and then influence policymakers to initiate reforms that make essential medical and preventive services universally available.

Competitive Medical Plans↗

Hematopoietic growth factors in autologous bone marrow transplantation.

The availability of recombinant human hematopoietic growth factors (rhHGFs) for clinical use has the potential to significantly decrease the morbidity and cost of autologous bone marrow transplantation (ABMT) and to make this therapeutic modality available to a broader patient population. Three rhHGFs currently have Food and Drug Administration-approved indications, although only one has a specific indication for ABMT. Recombinant human granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor have been used in several trials of ABMT. Recombinant human erythropoietin is less well studied to date in the setting of ABMT. Several investigational rhHGFs, including interleukin-3, -6, and -11, PIXY 321 (a granulocyte-macrophage colony-stimulating factor/interleukin-3 hybrid), and kit ligand (also known as "stem cell factor"), have the potential for affecting multiple lineages.

Bone Marrow Transplantation↗

Hematopoietic growth factor induction of gamma-glutamyl transferase in the KG-1 myeloid cell line.

The enzyme gamma-glutamyl transferase (GGT) is a multifunctional enzyme that participates in a number of metabolic processes, including the conversion of leukotriene C4(LTC4) to leukotriene D4(LTD4). LTD4 is necessary for normal myeloid proliferation and differentiation. We have examined the ability of hematopoietic growth factors (HGF) to induce GGT enzyme activity and mRNA content in a HGF-responsive cell line (KG-1). Incubation of KG-1 with recombinant human cytokines interleukin-1 beta (IL-1 beta), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF), but not interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) or monocyte colony-stimulating factor (M-CSF), results in significant increases in GGT enzyme activity. The increases in GGT activity are both dose- and time-dependent. In response to IL-1, increases in enzyme activity are seen by 6 hours and activity is maximal by 24 hours. GGT mRNA increases also occur and peak by 3 to 6 hours. These results indicate that induction of increases in GGT mRNA levels and enzyme activity occur in myeloid cells in response to HGFs. This induction, together with the requirement for LTD4 for normal granulopoiesis, supports a role for GGT in the cellular events occurring in myeloid cells in response to HGFs.

Antibodies↗

Mammography in women > or = 50 years of age. Predisposing and enabling characteristics.

The purpose of this study was to identify the relationship of selected predisposing and enabling characteristics of women > or = 50 years of age to mammography utilization. Andersen and Aday's theoretical model for health services utilization guided data collection. Data were collected from a convenience sample of 161 women members of four urban churches, using a mailed survey. Results showed that 81% reported at least one mammogram and 24% had followed mammography guidelines for the preceding 3 years. Results of logistic regression analyses with variables having a bivariate significance of p < or = 0.01 showed that higher income was associated with both ever having a mammogram and adherence. Willingness to pay > $50 out of pocket for a mammogram was significant for 3 year adherence. Additionally, the sociodemographic variables of age and religion were associated with adherence, whereas a college education was highly significant (odds ratio = 13.78) for ever having a mammogram. Having a regular place for health care and having yearly Papanicolaou tests were associated with ever having a mammogram, but not adherence. Finally, intending to get a mammogram was associated with ever having a mammogram. In this study, belief and knowledge variables showed no association with utilization, and social influence had bivariate significance only for ever having a mammogram. This study suggests the importance of addressing economic and health-care delivery system factors to promote increased mammography utilization, particularly for older women.

Aged↗

Public policy analysis for registered nurses in a baccalaureate curriculum.

As nurses become more involved in the macro-decision-making arena, they need policy analysis skills in order to make effective recommendations on policy alternatives. Dunn's policy analysis framework, useful for examining and understanding policy issues, is relevant to nursing education and practice and provides guidance for effective action. This framework guided an educational experience for registered nurse (RN) students in a baccalaureate nursing program. The students participated in community-based policy analysis, examining public policies affecting the health of individuals, families, groups, and populations. Dunn's framework and this policy experience can be incorporated into formal education courses or continuing education programs.

Curriculum↗

Patterns of uterine activity after intravaginal prostaglandin E2 during preinduction cervical ripening.

In a randomized study, uterine activity patterns were characterized with a portable pressure-sensitive device in 40 nonlaboring women at term with an unfavorable cervix who were undergoing preinduction cervical ripening with prostaglandin E2. The prostaglandin E2 was inserted into the posterior vaginal fornix as a single dose of either a 2.5 mg methylcellulose gel (20 cases) or 10 mg controlled-release pessary (20 cases). Uterine activity monitoring began 1 hour before dosing and continued for 12 hours. For those treated with the gel, low-amplitude, high-frequency contractions began within the first hour, reached a peak within 4 hours, and initiated sustained high-amplitude contractions in 10 (50%) cases. With the controlled-release pessary, low-amplitude, high-frequency contractions had a slightly later onset, reached a peak between the fifth and eighth hours, and initiated sustained high-amplitude contractions in 18 (80%) cases. Uterine hyperstimulation occurred in two (10%) pessary cases, with no adverse effect after removal. We conclude that low-amplitude, high-frequency uterine contractions began with either method of intravaginal prostaglandin E2 delivery but led to sustained, high-amplitude contractions primarily with the pessary.

Administration, Intravaginal↗

Histochemical quantitation of gamma-glutamyl transferase in human leukemia cell lines.

The enzyme gamma-glutamyl transferase (gamma-GT) is involved in many biochemical systems, including the signal transduction of hematopoietic growth factors. Standard colorimetric gamma-GT assays require larger cell numbers than may be obtainable in many cases, such as with highly purified stem-cell populations. To study gamma-GT expression in limited populations, we used a histochemical stain to analyze gamma-GT semiquantitatively in cells of hematopoietic origin. Several human leukemic cell lines, including one with inducible increases in gamma-GT, were stained for gamma-GT and graded 0 through 4+ for the amount of positive granules. The gamma-GT activity demonstrated by this stain was found to be directly proportional to the gamma-GT activity obtained with a colorimetric assay and could be used to calculate approximate gamma-GT activity. This stain therefore provides a useful method for determining gamma-GT activity when limited cell numbers are available.

Colorimetry↗

Regulation of HL-60 differentiation by lipoxygenase pathway metabolites in vitro.

We have studied the effects of lipoxygenase inhibition and metabolite addition of HL-60 cells induced to differentiate. When HL-60 are induced by dimethyl sulfoxide (DMSO) in the presence of an inhibitor of lipoxygenase, caffeic acid, there is a marked change from the expected phenotype of mature granulocytes to a population composed predominantly of mature monocytes. (DMSO alone: 54% granulocytes, 10% monocytes; DMSO + caffeic acid: 23% granulocytes, 53% monocytes.) Addition of leukotriene D4 to DMSO-induced, caffeic acid-inhibited cultures resulted in a dose-dependent recovery of the granulocyte phenotype. Addition of lipoxygenase inhibitors to phorbol ester-treated HL-60 cells did not alter the expected monocytic differentiation. These results support a role for leukotriene D4 in the regulation of granulocyte differentiation of HL-60 cells induced with DMSO.

Caffeic Acids↗

Flecainide excretion in human breast milk.

Healthy human volunteers who intended not to breast feed were placed on a regimen of 100 mg oral flecainide every 12 hours for 5 1/2 days beginning 1 day after parturition. Milk and blood samples were collected during the dosing period and for 2 days after the last dose. Concentrations of flecainide in milk and plasma were assayed by HPLC. Apparent steady-state levels of flecainide in both milk and plasma were achieved in most cases by day 4 of the study. Highest daily average concentration of flecainide in milk ranged from 270 to 1529 ng/ml for the 11 subjects. Mean +/- SD milk to plasma flecainide ratios were 3.7 +/- 3.5, 3.2 +/- 2.3, 3.5 +/- 2.1, and 2.6 +/- 0.7 on study days 2, 3, 4, and 5, respectively. After the last dose of flecainide, peak milk levels of the drug occurred at 3 to 6 hours and then declined monoexponentially. The half-life for elimination of flecainide from milk was 14.7 +/- 3.5 hours and is very similar to the plasma elimination half-life of flecainide in healthy human subjects. The mean milk to plasma ratios for flecainide after the last dose were 2.3 +/- 1.0 and 2.9 +/- 1.1 at 24 and 48 hours after the dose, respectively. Based on the pharmacokinetics of flecainide in infants, the expected average steady-state plasma concentration of flecainide in a newborn infant consuming all of the milk production of its mother (approximately 700 ml/day) would not be expected to exceed about 62 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Oocyte recovery, maturation and fertilization in vitro in the puma (Felis concolor).

Eight female pumas were treated i.m. with 1000 (N = 5) or 2000 (N = 3) i.u. PMSG followed 84 h later by 800 i.u. hCG. Eggs were recovered 24-26 h after hCG from ovarian follicles by using laparoscopy and transabdominal aspiration. Mature eggs were inseminated in vitro 4-6 h later whereas immature eggs were cultured for 24 h and then inseminated. Electroejaculates from 3 pumas were diluted with mKRB before insemination to evaluate the influence of sperm concentration on fertilization. Seven of 8 pumas responded with follicle development, and 140 eggs were recovered from 145 follicles (96.6%; 77 mature, 43 immature, 20 degenerate eggs; mean +/- s.e.m., 20.0 +/- 5.9 eggs/female). Overall fertilization rate was 43.5% (total eggs fertilized = 40) despite using inseminates containing 82-99% pleiomorphic spermatozoa. Of the 36 immature oocytes matured in vitro and inseminated, 12 were fertilized even though 50% of the inseminating spermatozoa contained an acrosomal defect. Fertilization rate of mature oocytes collected from follicles appeared unrelated (P greater than 0.05) to PMSG dose or number of spermatozoa/inseminate. This study demonstrates that a high proportion of follicular eggs can be recovered laparoscopically from adult pumas treated with PMSG and hCG. These gametes are capable of being fertilized in vitro (immediately or after maturation in vitro) even with low quality semen with a high incidence of sperm pleiomorphisms.

Animals↗

In vitro fertilization of gonadotropin-stimulated leopard cat (Felis bengalensis) follicular oocytes.

Based on techniques developed for the domestic cat, in vitro fertilization (IVF) studies were conducted in the taxonomically related leopard cat (Felis bengalensis). Adult females received pregnant mares' serum gonadotropin (PMSG) followed 80 or 84 h later by human chorionic gonadotropin (hCG) on two to four occasions over a 40-day to 27-month interval. Oocytes were collected laparoscopically from ovarian follicles 25-27 h after hCG and co-cultured with processed, homologous spermatozoa (37 degrees C, 5% CO2 in air, humidified atmosphere) for 30-36 h. There was no apparent ovarian refractoriness to repeated treatments with exogenous gonadotropins. Overall, the mean number of mature follicles present and the total number of oocytes and proportion of immature oocytes collected did not differ (P greater than 0.05) between the 80 h (4.9 +/- 0.9; 4.7 +/- 1.2; 14.9%, respectively) and 84 h (5.6 +/- 1.4; 5.4 +/- 1.7; 22.2%, respectively) gonadotropin interval groups. However, the proportion of mature leopard cat oocytes fertilized in vitro, as determined by embryonic cleavage, was increased (P less than 0.005) by extending the interval between PMSG and hCG from 80 (17.5%) to 84 (52.4%) h. These data 1) demonstrate that, compared to the domestic cat, the ovaries of the leopard cat are less responsive to a given PMSG/hCG treatment; 2) indicate that leopard cat follicular oocytes can be recovered readily by laparoscopy and are capable of becoming fertilized in vitro; and 3) suggest that IVF may be a viable approach for producing embryos and perhaps enhancing captive propagation of rare Felidae.

Animals↗