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Biomedical subjects

J R Miller

Publications and source records attributed to J R Miller.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Multidisciplinary home rehabilitation. A practical model.

The home is the most natural setting for rehabilitation. At home, the patient and family become active team members and the plan of care is created and carried out in the environment in which the patient will live. Home rehabilitation enhances the patient's autonomy, independence, and community reintegration.

Aged↗
PubMed1990

The beta-lactam biosynthesis genes for isopenicillin N epimerase and deacetoxycephalosporin C synthetase are expressed from a single transcript in Streptomyces clavuligerus.

Isopenicillin N isomerase (epimerase) has been purified from Streptomyces clavuligerus, and the amino acid sequence of the N-terminus has been determined. By using single oligonucleotide probes based on high GC codon bias ("guessmers"), the translation start codons were determined for two successive genes in the beta-lactam-biosynthetic pathway and mapped within a 3.6-kilobase-pair KpnI restriction fragment. The epimerase gene (cefD) was located immediately upstream of the deacetoxycephalosporin C synthetase (expandase) gene (cefE) that was characterized previously. cefD was sequenced and expressed in Escherichia coli; the resulting cell extracts contained epimerase activity. Western immunoblots demonstrated that a protein comigrated with purified S. clavuligerus epimerase at 44 kilodaltons. cefD and cefE were separated by an 81-base-pair segment. The DNA sequence upstream of the epimerase gene had a high AT content, suggestive of a promoter region. Primer extension analysis of S. clavuligerus mRNA showed that the start of transcription occurred approximately 130 base pairs upstream of the epimerase translation start site; Northern (RNA blot) analysis revealed a hybridization signal large enough to code for both epimerase and expandase, and nuclease S1 protection assays showed that a single message may code for epimerase, expandase, and another unknown protein. When cefD and cefE were placed in an expression vector, concomitant synthesis of both epimerase and expandase occurred in E. coli.

Amino Acid Isomerases↗
PubMed1990

Characterization of a D-amino acid oxidase with high activity against cephalosporin C from the yeast Trigonopsis variabilis.

We describe an improved method to purify D-amino acid oxidase with activity towards cephalosporin C. The protein has a carbohydrate content of 1.3% and two molecules of non-covalently bound flavin cofactor per protein molecule. HPLC profiles and enzymatic analysis have indicated that the cofactor is FAD, even though fluorescence spectroscopy shows a slightly altered spectral profile in the 400-500 nm range compared to authentic FAD. N-terminal sequencing of the protein revealed a high level of similarity (56% identity in 25 amino acids) between the fungal and mammalian oxidase, and probably represents a "Rossman fold" with a beta-alpha-beta structure for the binding of the adenosyl moiety of the cofactor.

Amino Acid Sequence↗
PubMed1979

Antenatal diagnosis of neural tube defects in Canada: extension of a collaborative study.

Experience with the diagnosis of neural tube defects from alpha1-fetoprotein (AFP) concentrations in amniotic fluid is reported from a prospective study of five laboratories testing for 13 Canadian genetic centres. The results of the study indicate that antenatal diagnosis of open neural tube defects is being carried out effectively in Canada (in 99.2% of cases the AFP measurements were interpreted correctly). Amniocentesis should be recommended to women at high risk for having a child with a neural tube defect (i.e., those who have a child, a parent or a sibling with a neural tube defect). The rate of neural tube defects in 182 high-risk pregnancies was 2.2% for an open defect and 1.1% for a closed defect, whereas the rate in 673 pregnancies in which amniocentesis was being performed for other reasons was 0.3%. This suggests that the AFP concentration should be measured in any sample of amniotic fluid collected for other reasons (usually fetal karyotyping). There were three instances of false-negative results, for a rate of 0.4%. Two closed neural tube defects were not detected; this limitation of the test has also been found by others. One of the six fetuses with an open neural tube defect, who died in utero, had a large myelocele in the neck that was not recognized. There were also four instances of false-positive results, for a rate of 0.5%. The findings suggest that AFP values that are more than 2 but less than 7 standard deviations (SDs) above the mean may indicate a neural tube defect, and that values 7 or more SDs above the mean very likely indicate such a defect, although other reasons for such high values (e.g., fetal erythrocytes in the amniotic fluid, intrauterine death and mistaken gestational age) must be ruled out by other methods.

Amniocentesis↗
PubMed1979

Apparent validity of alternative survey methods.

A comparison of results using three methods of obtaining the same survey data is reported. The assumption is made that in relation to a question for which there is a socially desirable response, e.g., use of seat restraints for children, those reporting nonuse or infrequent use are giving truthful answers. In an experiment in health education, follow-up assignments were made randomly, one third being interviewed face-to-face, one third by telephone, and the rest by a postal questionnaire. There were no significant differences by method of follow-up in the scores reflecting reported changes in behavior following instruction. Both the telephone and mail methods, however, appear to yield a higher proportion of "truthful", i.e., socially undersirable, responses; 30.4% of those contacted by telephone admitted to not using a restraint on the last trip, compared with 26.3% of those questioned by mail and 17.5% in a household interview. It is recommended that careful consideration be given to these alternative methods of obtaining data, particularly in view of their lower cost and possibly greater validity.

Child↗
PubMed1979

Optimization of parameters in protein nitrogen unit precipitation procedure for allergenic extracts.

This work establishes the optimum conditions for the protein nitrogen unit (PNU) phosphotungstic acid (PTA) precipitation procedure for allergenic extracts. The volume of extract analyzed, the dilution of the extract prior to precipitation, the percent PTA in the precipitating solution, the washing of the precipitate, and the volume of concentrated HCl initially added to the extract were optimized, as they were found to be the factors which affected the amount of PTA precipitate obtained. Varying the digestion time, the digestion temperature, and the percent HCl in the 15% PTA precipitating solution did not cause detectable differences in the PNU values of the extracts studied.

Allergens↗
PubMed1979

Monozygotic twinning and structural defects.

An excess of structural defects occurs in monozygotic twins compared in dizygotic twins or singletons. The excess is composed of three categories of defects. The first includes defects which are part of the MZ twinning, such as conjoined twins and some amorphous twins. In addition, all early embryonic malformations and malformation complexes such as sirenomelia mc. holoprosencephaly mc. and anencephaly mc are increased in MZ twins. The reason for this association is considered to be the common etiology for both the MZ twinning and the early malformation problem. MZ twins provide an excellent model for appreciating the spectra of particular malformation complexes, since the twins often have different gradations in severity of the same type of structural defect. The finding of both discordant and concordant MZ twins with Goldenhar, de Lange, and Rubinstein-Taybi syndromes suggests that these "syndromes" might be early malformation complexes. The other two categories are considered secondary to the MZ twinning process. The most unique category results from any vascular interchange between the MZ twins. Depending on their nature, vascular connections may give rise to reverse flow with acardiac status in one twin during early development, or to vascular disruptions from a deceased co-twin with intravascular coagulation causing embolization in the surviving co-twin. The latter defects may include microcephaly, porencephalic cysts, hydranencephaly, intestinal atresia, aplasia cutis, and limb amputation. Unequal growth may occur as a result of artery to vein placental anastomoses. The final category is deformations due to crowding in utero during late gestation. These do not differ from those in DZ twins.

Cardiovascular Abnormalities↗