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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 181 records · Page 10Linked to original sources
PubMed1998

Expressed sequenced tags and new genes from the cattle tick, Boophilus microplus.

We used the expressed sequenced tags (ESTs) approach to study the genome of the cattle tick Boophilus microplus. One hundred and forty-two of our 234 unique ESTs were from genes not previously identified from ticks, mites or any other arachnids. The largest class of identified ESTs (29%) was from genes involved in transcription and translation. Ninety-one ESTs (39% of all ESTs) did not match any sequences in international databases; some of these may be specific to ticks. Thirteen percent of our ESTs were from ribosomal proteins and two ESTs were for genes implicated in resistance to pesticides.

Animals↗
PubMed1998

CD34+ stem cell augmentation of elutriated allogeneic bone marrow grafts: results of a phase II clinical trial of engraftment and graft-versus-host disease prophylaxis in high-risk hematologic malignancies.

Although T cell depletion of allografts used in BMT has reduced GVHD, it has been associated with inferior engraftment and an increased risk of relapse. We have found that T cell depletion by counterflow centrifugal elutriation (CCE) also results in depletion of CD34+ stem cells. In order to determine if the discarded CD34+ cells would improve engraftment, we undertook a phase II trial of allogeneic BMT in which 110 patients (median age 43) with a variety of hematologic malignancies received CD34+ stem cell augmented, elutriated marrow grafts. The T cell-depleted grafts were tightly controlled and contained a mean of 4.3 x 10(7) mononuclear cells/kg, 3.3 x 10(6) CD34+ cells/kg, 1.5 x 10(5) CFU-GM/kg and 5.5 x 10(5) CD3+ T cells/kg. Median time to engraftment of granulocytes (>500/microl) was 16 days and of platelets (>50000/microl) was 25 days, comparable to that seen with unmanipulated marrow. No mixed hematopoietic chimerism was observed that was not associated with disease relapse. The four patients (3.6%) who failed to engraft were all at high risk because of prior donor transfusions or underlying marrow disorders. The incidence of GVHD was dependent on the duration of cyclosporin A (CsA) immunosuppression. In patients who received CsA for > or = 80 days, the incidence of clinically significant acute GVHD (>stage 1) and extensive, chronic GVHD was 5% and 11%, respectively. Peritransplant (< or = 100 day post-BMT) mortality for this group of patients was 15%. Event-free survival in selected subsets of patients compared favorably to previous studies in which patients received unmanipulated marrow allografts.

Adolescent↗
PubMed1998

Cerebrospinal fluid shunt infections in infants and children in Mobile, Alabama.

Cerebrospinal fluid shunt systems are used to treat hydrocephalus in infants and children; unfortunately, some shunt systems become infected. We sought to define the epidemiology of shunt infections and shunt survival prior to infection at our institution. We identified 268 shunt procedures performed from January 1990 to June 1996 in 145 patients. There were 29 episodes of shunt infection for an incidence of 10.8% per procedure and 13.1% per patient. Staphylococcus epidermidis was the most common isolate recovered. The probability of shunt infection was highest during the first 8 weeks after a shunt procedure and subsequent infection was less likely after 28 weeks.

Adolescent↗
PubMed1998

Functional reconstitution of a prokaryotic K+ channel.

SliK, a K+ channel encoded by the Streptomyces KcsA gene, was expressed, purified, and reconstituted in liposomes. A concentrative 86Rb+ flux assay was used to assess the ion transport properties of SliK. SliK-mediated ionic flux shows strong selectivity for K+ over Na+ and is inhibited by micromolar concentrations of Ba2+, mirroring the basic permeation characteristic of eukaryotic K+ channels studied by electrophysiological methods. 86Rb+ uptake kinetics and equilibrium measurements also demonstrate that the purified protein is fully active.

Algorithms↗
PubMed1998

Analysis of synthetic peptides by capillary zone electrophoresis in organic/aqueous buffers.

Whereas synthetic peptides have been routinely analyzed for purity by reverse phase high performance liquid chromatography (RPHPLC) for a number of years, it is only in the last decade that the use of capillary zone electrophoresis (CZE) in aqueous buffers has been taken advantage of as an orthogonal method for the detection of impurities. However, we have found that hydrophobic amino acids and peptides often migrate as very broad, tailing absorbances or even precipitate in the aqueous buffers during CZE analysis. As a result, alternative buffer systems containing organic modifiers were sought. Varying concentrations of acetonitrile, methanol and isopropanol in sodium phosphate and triethylammonium phosphate buffers were used to study their effects on the electrophoretic migration of several synthetic peptides [gonadotropin releasing hormone (GnRH), corticotropin releasing factor (CRF) and analogs] and an enantiomeric synthetic amino acid. The organic/aqueous buffers used to obtain the best conditions for separation of porcine gonadotropin-releasing hormone (GnRH) and chicken II GnRH were then used to optimize a separation of nine native forms of GnRH decapeptides. Interestingly, several of these GnRHs have identical formal charges and yet could be separated. This suggests a mixed mechanism of separation that discriminates not only on the basis of peptide charge and structure but also of adsorptive properties (Van der Waals forces, dipole-dipole interactions and hydrogen bonding) of the capillaries.

Buffers↗
PubMed1998

Deadbeat dads or inept states? A comparison of child support enforcement systems.

This article provides information on the effectiveness of state child support enforcement systems. We use individual level data from the Child Support Supplements of the Current Population Surveys (1978-1992) to create an index of state effectiveness that captures success at securing child support awards, setting award levels, and collecting obligations. We identify states that were performing above or below the national average in the late 1980s to early 1990s and states that showed substantial improvement or decline in child support effectiveness during the 1980s. Identifying successful states will help researchers to determine what policies and practices are associated with successful enforcement. These variations in state effectiveness also suggest that low levels of child support are not due to deadbeat dads alone but also to inept states.

Child↗
PubMed1998

Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract.

The murine female reproductive tract differentiates along the anteroposterior axis during postnatal development. This process is marked by the emergence of distinct cell types in the oviduct, uterus, cervix and vagina and is dependent upon specific mesenchymal-epithelial interactions as demonstrated by earlier heterografting experiments. Members of the Wnt family of signaling molecules have been recently identified in this system and an early functional role in reproductive tract development has been demonstrated. Mice were generated using ES-mediated homologous recombination for the Wnt-7a gene (Parr, B. A. and McMahon, A. P. (1995) Nature 374, 350-353). Since Wnt-7a is expressed in the female reproductive tract, we examined the developmental consequences of lack of Wnt-7a in the female reproductive tract. We observe that the oviduct lacks a clear demarcation from the anterior uterus, and acquires several cellular and molecular characteristics of the uterine horn. The uterus acquires cellular and molecular characteristics that represent an intermediate state between normal uterus and vagina. Normal vaginas have stratified epithelium and normal uteri have simple columnar epithelium, however, mutant uteri have stratified epithelium. Additionally, Wnt-7a mutant uteri do not form glands. The changes observed in the oviduct and uterus are accompanied by a postnatal loss of hoxa-10 and hoxa-11 expression, revealing that Wnt-7a is not required for early hoxa gene expression, but is required for maintenance of expression. These clustered hox genes have been shown to play a role in anteroposterior patterning in the female reproductive tract. In addition to this global posterior shift in the female reproductive tract, we note that the uterine smooth muscle is disorganized, indicating development along the radial axis is affected. Changes in the boundaries and levels of other Wnt genes are detectable at birth, prior to changes in morphologies. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anteroposterior and radial axes of the female reproductive tract.

Animals↗
PubMed1998

Supporting practitioner research in speech and language therapy.

This paper discusses the characteristics of action research and promotes its potential for speech and language therapists. Action research is an approach which involves the practitioner and has as its purpose the improvement of practice. Small-scale studies by practitioners can be used to examine practical applications and implications of larger-scale studies. A group of therapists, motivated by a wish to investigate their own practice, proposed the development of a group to support their work, facilitated by the author.

Humans↗
PubMed1997

Betidamino acid scan of the GnRH antagonist acyline.

Strong clinical evidence suggests that GnRH antagonists will replace GnRH agonists in a number of indications because of their ability to inhibit gonadotropin secretion as long as an adequate concentration of the analogue is present in the circulation whereas superagonists will take approximately 2 weeks to desensitize the gonadotrophs. Until recently, antagonists were either too weak and/or would release histamine. Azaline B {[Ac-D2Nal1,D4Cpa2,D3Pal3, 4Aph5(atz),D4Aph6(atz),ILys8,DAla10] GnRH} and long-acting members of the azaline family {Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(X)-D4Aph(Y) -Leu-ILys-Pro-DAla-NH2}, however, appear to be promising drug candidates. Because these antagonists tend to form gels (due to the formation of beta-sheet structures) and, as a result, are not readily amenable to formulation for long-term delivery, we have investigated ways of increasing hydrophilicity while retaining high potency and lack of histamine releasing activity. Betidamino acids (a contraction of "beta" position and "amide") are N'-monoacylated (optionally, N'-monoacylated and N-mono- or N,N'-dialkylated) aminoglycine derivatives in which each N'-acyl/alkyl group may mimic naturally occurring amino acid side chains or introduce novel functionalities. We have used unresolved N alpha-Boc,N'alpha-Fmoc-aminoglycine, and N alpha-Boc,N'alpha-(CH3)Fmoc-aminoglycine as templates for the introduction of betidamino acids in acyline (Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(Ac)-D4Aph(A c)-Leu-Ilys-Pro-DAla-NH2), a long acting member of the azaline B family, to test biocompatibility of these betide derivatives. Diastereomeric peptides could be separated using RP-HPLC in most cases. Biological results obtained in vitro (binding affinity to rat pituitary gland membranes) and in vivo (rat antiovulatory assay, AOA) indicate in most cases small differences in relative potencies (< 5-fold) between the D- and L-nonalkylated betidamino acid-containing acylines. Importantly, most betide diastereomers have high affinity for the GnRH receptor and were equipotent with acyline in the AOA. Greater differences in affinity and potency between diastereomers were observed after introduction of a methyl group on the side chain nitrogen ("beta" position) of the same analogues, with one of the diastereomer having an affinity and a potency in the AOA equivalent to that of acyline. These results suggest that chirality at the alpha-carbon coupled to side chain orientation is important for receptor recognition. The duration of action of some of the most potent analogues was also determined in the castrated male rat in order to measure the extent (efficacy and duration of action) of inhibition of luteinizing hormone release. Data suggest that introduction of a betidamino acid results in reduction of duration of action. Also, introduction of betidamino acids results in peptides with increased hydrophilicity (as determined by elution times on C18 silicas at pH 7.3) compared to that of the parent compound. N'-Methyl substitution results in parallel increase in retention times on C18 silicas as expected.

Amides↗
PubMed1997

A graphical assessment of the potential impact of losses to follow-up on the validity of study results. The Terry Beirn Community Programs for Clinical Research on AIDS.

Losses to follow-up in clinical trials-patients for whom we do not know if the outcome of interest has occurred-can bias study results. If we investigate extreme case scenarios and find the study results do not change much, impact is negligible. If not, we may need to interpret the study's results with caution. At issue is how much caution do we need? We describe a graphical approach to assess the potential impact of losses to follow-up on the validity of study results. One can create the graphs using design estimates and interim or final data. We give two examples using design parameters and another example modelled after observed data from clinical trials conducted by the Terry Beirn Community Programs for Clinical Research on AIDS. The examples illustrate that tolerable levels of losses to follow-up change depending on the overall outcome and direction of differential losses.

Bias↗