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Biomedical subjects

J R Miller

Publications and source records attributed to J R Miller.

At least 109 records · Page 6Linked to original sources

Neonatal mortality following transfusion of red cells with high plasma potassium levels.

The death of a neonatal infant following cardiac surgery and the transfusion of packed red cells (RBCs) with high plasma potassium levels is reported. The patient had been diagnosed at 2 weeks of age as having multiple cardiac malformations. During cardiopulmonary bypass surgery, multiple units of packed RBCs less than 5 days old were transfused. In response to a "stat" order and after depletion of stock units prepared for neonatal usage, a 32-day-old unit of packed RBCs was issued for transfusion. After approximately 60 mL was rapidly transfused from this unit, the patient experienced cardiac arrest. Serum potassium concentration after transfusion and before death was 8.9 mmol per L. Plasma potassium concentration in the remainder of the transfused packed RBC unit was approximately 60 mmol per L. A model was created to calculate the posttransfusion plasma potassium concentration, and close correlation was found between the model and the observed potassium concentration, which assumes that the potassium load had not yet been distributed to the extravascular and intracellular fluid compartments. It is concluded that the transfusion of relatively large volumes of RBCs be limited to fresh packed RBCs or to packed RBCs that have been saline washed, to minimize the complications of electrolyte disturbances.

Blood Component Transfusion↗

Designing for the future.

The American Organization of Nurse Executives (AONE) is the national organization of nurse executives and nurse managers. AONE provides leadership, professional development, advocacy, and research to advance nursing practice and patient care, promote nursing leadership excellence, and shape healthcare public policy. This column, written by officers and executive staff members of AONE, raises issues and discusses trends of importance to nursing administrators.

Humans↗

Synteny mapping in the horse using horse-mouse heterohybridomas.

In a study of 35 horse-mouse heterohybridoma cell lines, synteny in the horse was found between LDHB, PEPB and IGF1 and between NP, MPI and IDH2. A synteny between ADA and PEPC was also indicated. The loci for horse immunoglobulin light chain (IgL) genes and for LDHA were independent.

Adenosine Deaminase↗

A chromosomal basis for the differential organization of a porcine centromere-specific repeat.

Digestion of porcine DNA with the restriction enzymes SnoI and BamHI and subsequent gel electrophoresis revealed the presence of a repeat fragment of approximately 340 bp in length. When this fragment was cloned and used to probe a Southern blot containing pig DNA that had been digested with various enzymes, a ladder pattern of bands based on a unit of 340 bp was observed. Three individual BamHI repeat units were sequenced; each monomer unit was approximately 90% identical in sequence to the other two monomers. Double digestion did not alter the ladder pattern, indicating a differential distribution of restriction enzyme sites within the repeat family. We demonstrate by Southern blotting of DNAs from a panel of pig x rodent hybrid cell lines that the differential restriction site distribution has a chromosomal basis. We show that this repeat family hybridizes to the centromeres of all pig chromosomes other than the Y chromosome. However, when stringency was raised, hybridization persisted only to certain metacentric chromosomes.

Animals↗

SCH 45752--an inhibitor of calmodulin-sensitive cyclic nucleotide phosphodiesterase activity.

A highly potent inhibitor of calmodulin-sensitive phosphodiesterase (PDE) activity was isolated from the culture broth of an unidentified fungal isolate, SCF-125. A chemically defined medium was developed for production of this compound. The PDE inhibitor was isolated from the fermentation filtrate by adsorption on a macro-reticular resin and further purified by gel filtration chromatography and reverse-phase HPLC. The major PDE inhibitor was identified as cephalochromin, a bis-naphthopyrone, by spectral data analysis. The compound, SCH 45752, inhibited calmodulin-sensitive PDE activities with IC50 values of 40-47 nM. It inhibited the activities of calmodulin-independent PDE and various protein kinases with higher IC50 values (2-40 microM). SCH 45752 does not appear to be a calmodulin antagonist. Furthermore, SCH 45752 affects smooth muscle contraction at a concentration of 30 microM; it potentiated the relaxing effect of sodium nitroprusside on carotid artery media contracted by histamine. Thus SCH 45752 is one of the most potent inhibitors of calmodulin-sensitive PDE activity known, and it is capable of exerting a pharmacological effect in at least one intact tissue model.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Botulinum toxin for the treatment of spasticity in multiple sclerosis. New observations.

Potential advantages of intramuscular botulinum toxin for the treatment of spasticity include the lack of sensory effects, ability to target specific muscle groups, ability to weaken muscles in a graded fashion and absence of caustic chemicals such as phenol. We describe the use of botulinum toxin for the treatment of severe lower extremity spasticity in two subjects with multiple sclerosis. Both subjects showed an improvement in spasticity, as measured by the modified Ashworth scale, and in functional status. Both subjects exhibited reductions in muscle tone not only in injected muscles, but also in noninjected muscles in the region. These more distant clinical effects have not been emphasized in previous studies after therapeutic injections of botulinum toxin. Further research is needed to clarify the cause and prevalence of these regional motor effects, as well as to further examine the safety and efficacy of botulinum toxin for spasticity treatment.

Activities of Daily Living↗

In vitro and in vivo pharmacological characterization of N6-cyclopentyl-9-methyladenine (N-0840): a selective, orally active A1 adenosine receptor antagonist.

The pharmacological and biochemical profile of N6-cyclopentyl-9-methyladenine (N-0840) was elucidated in vitro and in vivo. In radioligand binding assays, N-0840 had 14- to 400-fold greater affinity for A1 than A2 adenosine receptors and did not inhibit radioligand binding to alpha-1, alpha-2, beta, 5-hydroxytryptamine 1a, muscarinic, D1 or D2 receptors at concentrations < or = 10,000 nM. In guinea pig tissues, N-0840 competitively antagonized A1 receptor-mediated, 5'-N-ethylcarboxamidoadenosine-induced negative inotropism (paced left atria, KB = 0.83 microM), chronotropism (spontaneously beating right atria, KB = 0.91 microM) and dromotropism (Langendorff heart; KB = 0.72 microM). However, at concentrations up to 100 microM, N-0840 did not antagonize A2 adenosine receptor-mediated, 5'-N-ethylcarboxamidoadenosine-induced relaxations of the guinea pig aorta. N-0840 was a poor inhibitor of total cyclic nucleotide phosphodiesterase activity and of adenosine uptake (IC50 > 200 microM), and it did not inhibit adenosine deaminase activity. In anesthetized rats, N-0840 selectively antagonized A1 adenosine receptor-mediated bradycardia, but generally failed to affect A2 adenosine receptor-mediated vasodilation in the in situ perfused hindquarters (A2/A1 selectivity: > or = 33-fold). The duration of action of N-0840 ranged from 1 min (after 3 mumol/kg i.v.) to 8 hr (after 100 mumol/kg p.o.). N-0840 (< or = 100 mumol/kg i.v.; < or = 1,000 mumol/kg p.o.) had little or no effect on blood pressure or heart rate and produced no adverse drug reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗

Anti-sulfatide antibodies in neurological disease: binding to rat dorsal root ganglia neurons.

Increased titers of anti-sulfatide antibodies were detected by ELISA in 5 of 200 patients and control subjects. All 5 patients had sensory impairment; 4 had neuropathy, and one had multiple sclerosis. Of the patients with neuropathy, 2 had a clinical syndrome of small fiber sensory neuropathy with normal electrophysiological or nerve biopsy studies, 1 had a sensorimotor axonal neuropathy associated with IgM monoclonal gammopathy, and 1 had sensorimotor neuropathy with multifocal motor conduction block and anti-GM1 antibodies. The anti-sulfatide antibodies bound to the surface of unfixed rat dorsal root ganglia neurons and human neuroblastoma cells, and to fixed sections of central and peripheral myelin. No binding was detected following intraneural injection into rat sciatic nerves. Pre-absorption with sulfatide but not with galactocerebroside eliminated the tissue binding activity. These findings indicate that increased titers of anti-sulfatide antibodies are found in patients with sensory impairment but are not restricted to a particular neurological syndrome or type of neuropathy. The significance of anti-sulfatide antibodies is uncertain although sulfatide on dorsal root ganglia neurons may be a target antigen.

Aged↗

Progressive multifocal leukoencephalopathy in patients with human immunodeficiency virus.

Lesions of progressive multifocal leukoencephalopathy (PML) in patients infected with the human immunodeficiency virus (HIV) often have mononuclear cell infiltrates so intense that they obscure the nature of the lesion. This response may be especially prominent in stereotactic biopsies of contrast-enhancing areas. Of 10 consecutive PML lesions biopsied stereotactically, three were markedly, two were moderately, and five were mildly inflamed. There were few to no enlarged oligodendrocytic nuclei with inclusions in the markedly and moderately inflamed lesions. We investigated all biopsies with immunoperoxidase, DNA in situ hybridization, polymerase chain reaction, and Southern immunoblot methodologies for toxoplasmosis and the following viruses: JC, cytomegalovirus, herpes simplex viruses I and II, and human T-cell lymphotropic viruses I, II, and III. We confirmed the presence of JC virus in each lesion; polymerase chain reaction revealed HIV genome only in one. Inflammatory PML lesions in HIV+ patients do not reflect co-infection with toxoplasmosis or viruses commonly seen in these patients. The mononuclear cells are primarily T lymphocytes. Patients with severely inflamed PML lesions, whether HIV+ or not, often show stabilization of symptoms with or without antiviral treatment and have longer lengths of survival than patients with less inflamed lesions.

Adult↗

A chromosome 1-specific DNA library from the domestic pig (Sus scrofa domestica).

Chromosomes were prepared from lymphocytes of a male domestic pig and flow-sorted on a dual-laser FACS. Twenty spots were observed, corresponding to the known pig karyotype of 18 pairs of autosomes plus the X and Y. DNA was isolated from 10,000 copies of the presumed chromosome 1 spot, restricted with Sau3A, ligated into the vector pGEM4z, and PCR amplified using universal primers; the products were then re-ligated into pUC18. After transformation into Escherichia coli, 210,000 independent colonies were obtained, 5% of which contained only vector DNA. The average insert size of the library was 405 bp. Southern blotting revealed that 36% of the clones contained single-copy DNA and that the remainder contained moderately or highly repetitive DNA. Screening with a (CA)n probe revealed that roughly 1% of the clones contained microsatellite sequences. A bulk insert of the library was biotinylated by PCR and used as a probe for chromosomal in situ suppression hybridization to pig chromosomes, which confirmed that the library is specific for chromosome 1. However, sequences from the centromeric and telomeric regions seem to be underrepresented in the library.

Animals↗

Mapping of repetitive bovine DNA sequences on cattle Y chromosomes.

Three male-specific PCR products of the sequences BC1.2, lambda ES6.0, and BRY.1 were used as probes for Southern blot analyses. Each of these probes generated a complex male-specific band pattern, which showed some quantitative variations among bulls. Hybridization patterns obtained with the BC1.2 and lambda ES6.0 PCR products were interrelated. Chromosomal locations of these repeats were determined by hybridizing the tritiated PCR products in situ to male metaphase spreads. The BC1.2 and lambda ES6.0 PCR products hybridized to Yp13-->p12, whereas the BRY.1 PCR product hybridized over the entire Y chromosome. In addition, the BC1.2 and lambda ES6.0 PCR products hybridized to the distal half of the acrocentric Y chromosome of Bos indicus, indicating that the short arm of the B. taurus Y chromosome is homologous with the telomeric end of the B. indicus Y and supporting the notion that the Y chromosomes of these two species differ by a pericentric inversion.

Animals↗

The psychosocial aspects of rehabilitation.

Physical therapy is not only about the healing of the body; ramifications to the patient's and family's emotional and social lives also must be considered. The following case examples from Wellmark Healthcare Services, Inc. exemplify the positive results of addressing psychosocial issues in rehabilitation.

Adaptation, Psychological↗

Synteny mapping of the bovine IGHG2, CRC and IGF1 genes.

A panel of bovine-murine hybrid cell lines was analysed for 10 loci, including three (IGF1, IGHG2 and the calcium release channel gene [CRC]) that have previously been mapped in man, but not in cattle. The IGF and CRC genes were indirectly mapped to chromosomes 5 and 18 respectively and the syntenies of the HOX2 and GH genes and of the NP and FOS genes were confirmed. The results also show that the IGHG2 locus, which is linked to NP and FOS on human chromosome 14, is separated from these genes in cattle. By showing synteny of the IGHG2 and MPI loci, the IGHG2 locus has been indirectly mapped to chromosome 21.

Animals↗

A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants.

Modifiers of position-effect-variegation in Drosophila encode proteins that are thought to modify chromatin, rendering it heritably changed in its expressibility. In an attempt to identify similar modifier genes in other species we have utilized a known sequence homology, termed chromo box, between a suppressor of position-effect-variegation, Heterochromatin protein 1 (HP1), and a repressor of homeotic genes, Polycomb (Pc). A PCR generated probe encompassing the HP1 chromo box was used to clone full-length murine cDNAs that contain conserved chromo box motifs. Sequence comparisons, in situ hybridization experiments, and RNA Northern blot analysis suggest that the murine and human sequences presented in this report are homologues of the Drosophila HP1 gene. Chromo box sequences can also be detected in other animal species, and in plants, predicting a strongly conserved structural role for the peptide encoded by this sequence. We propose that epigenetic (yet heritable) changes in gene expressibility, characteristic of chromosomal imprinting phenomena, can largely be explained by the action of such modifier genes. The evolutionary conservation of the chromo box motif now enables the isolation and study of putative modifier genes in those animal and plant species where chromosomal imprinting has been described.

Amino Acid Sequence↗

Cloning and sequencing of the beta-lactam hydroxylase gene (cefF) from Streptomyces clavuligerus: gene duplication may have led to separate hydroxylase and expandase activities in the actinomycetes.

The deacetylcephalosporin C synthetase (hydroxylase) gene from Streptomyces clavuligerus has been cloned and sequenced. The open reading frame codes for a protein with an Mr of 34,584. The hydroxylase gene (cefF) is closely linked to the epimerase gene (cefD) and the expandase gene (cefE) and is transcribed in the opposite orientation. The hydroxylase and expandase genes are 59 and 71% identical at the amino acid and DNA levels, respectively. cefE and cefF may have arisen from a gene duplication in the actinomycetes.

Amino Acid Sequence↗

Localization of the lysine epsilon-aminotransferase (lat) and delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (pcbAB) genes from Streptomyces clavuligerus and production of lysine epsilon-aminotransferase activity in Escherichia coli.

Lysine epsilon-aminotransferase (LAT) in the beta-lactam-producing actinomycetes is considered to be the first step in the antibiotic biosynthetic pathway. Cloning of restriction fragments from Streptomyces clavuligerus, a beta-lactam producer, into Streptomyces lividans, a nonproducer that lacks LAT activity, led to the production of LAT in the host. DNA sequencing of restriction fragments containing the putative lat gene revealed a single open reading frame encoding a polypeptide with an approximately Mr 49,000. Expression of this coding sequence in Escherichia coli led to the production of LAT activity. Hence, LAT activity in S. clavuligerus is derived from a single polypeptide. A second open reading frame began immediately downstream from lat. Comparison of this partial sequence with the sequences of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D valine (ACV) synthetases from Penicillium chrysogenum and Cephalosporium acremonium and with nonribosomal peptide synthetases (gramicidin S and tyrocidine synthetases) found similarities among the open reading frames. Since mapping of the putative N and C termini of S. clavuligerus pcbAB suggests that the coding region occupies approximately 12 kbp and codes for a polypeptide related in size to the fungal ACV synthetases, the molecular characterization of the beta-lactam biosynthetic cluster between pcbC and cefE (approximately 25 kbp) is nearly complete.

Amino Acid Sequence↗