Appropriate eye drugs for developing countries.
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Developing Countries↗
Biomedical subjects
J Taylor
Publications and source records attributed to J Taylor.
A distinct HLA-DRw8 haplotype characterizes patients with juvenile rheumatoid arthritis.
We studied the first domain of the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci of 67 HLA-DRw8-positive Caucasians including 43 with early-onset pauciarticular juvenile rheumatoid arthritis (EOPA-JRA, alternatively known as early-onset pauciarticular juvenile chronic arthritis). Serology, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) oligotyping revealed that 62, including all the EOPA-JRA patients, carried the HLA-DRB1*0801, DQA1*0401, DQB1*0402 genotype. Approximately one-fifth of the controls carried atypical HLA-DRB1, HLA-DQA1, and/or HLA-DQB1 loci on their HLA-DRw8 haplotype confirmed by family studies. DNA sequences of HLA-DRB1, DQA1, and DQB1 alleles in patients and controls were identical to those previously reported. Disease association studies in 113 EOPA-JRA patients and 207 controls unselected for HLA-DRw8 revealed that the HLA-DRB1*0801, DQA1*0401, DQB1*0402 genotype was associated with a higher relative risk (RR) for disease (RR = 12.8, chi 2 = 48.8, P less than 10(-4)) than was the serologically defined presence of HLA-DRw8 (RR = 8, chi 2 = 39, P less than 10(-4)). Further analysis suggested that the DQ genes on HLA-DRw8 haplotypes are as likely as the DR genes to contribute to the pathogenesis of EOPA-JRA. This study increases to five the number of HLA-DR/DQ haplotypes identified in HLA-DRw8 Caucasians.
Arthritis, Juvenile↗
The estimation of small town Aboriginal population change.
"This paper outlines some of the methodological and conceptual issues associated with the estimation of Aboriginal population change in the rapidly growing town of Katherine, in the Northern Territory [of Australia], and reports on selected social and economic impacts of recent in-migration. Attention is drawn to the inappropriateness of de facto population figures as a basis for planning and the need to estimate service requirements in the context of high population mobility."
Australia↗
Protection of chickens with a recombinant fowlpox virus expressing the Newcastle disease virus hemagglutinin-neuraminidase gene.
A recombinant fowlpox virus expressing the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) strain Texas was generated. Immunoprecipitation with chicken anti-NDV serum confirmed authentic expression of the HN protein. Protection of chickens from infection with NDV was observed when birds were immunized with the recombinant HN fowlpox virus by the intramuscular route after one or two inoculations. Vaccination by the ocular route with a mixture of fowlpox recombinants expressing the fusion and HN proteins did not show added protection over that seen with the individual viruses.
Animals↗
Voluntary alcohol and cocaine consumption in "low" and "high" stress plasma catecholamine responding rats.
Alcohol (ethanol) and cocaine preference in a free-choice, two-bottle situation was measured in two groups of male and female "low" and "high" plasma catecholamine stress responding rats. Alcohol intake of a 5% solution (percent or mg/kg) showed markedly different but individually consistent intake among animals. "High" plasma catecholamine stress responders consumed more ethanol than did "low" responders. A similar finding was made when animals consumed a 10% solution; fluid intake fell but total ethanol intake remained the same. "High" responders drank more than did "low" responders. After a period of 4 weeks of water only, animals were reexposed to 5% ethanol and a significant positive correlation was seen in the drinking habits of the animals. Afterwards, exposure to a 0.02% cocaine solution resulted in cocaine intake which varied among animals, but was consistent for an individual rat and did not correlate with alcohol consumption. In general, ethanol and cocaine consumption correlated positively with the plasma catecholamine stress response. No significant differences in drinking habits were observed between the sexes. Thus, alcohol preference is a relatively stable characteristic of an animal, is higher in "high" as compared to "low" plasma catecholamine stress responders and does not correlate with voluntary cocaine consumption.
Alcohol Drinking↗
The analysis of recessive lethal mutations in mice by using two-dimensional gel electrophoresis of liver proteins.
We have used two-dimensional gel electrophoresis (2DE) coupled with computer-assisted data analysis to analyze liver-protein expression in mice known to be heterozygous carriers of recessive lethal mutations induced in In(1)1Rk or In(7)13Rk inversion stocks by exposure to either triethylene melamine or ionizing radiation. Carriers of 8 different mutations and corresponding littermate controls (average of 17 individuals in each group) were screened for liver-protein differences. Both qualitative and quantitative protein differences were detected that correlated with unique pedigrees among the mouse stocks analyzed. Such strain-specific differences demonstrated that quantitative differences (either increases or decreases) in protein abundance of greater than 25% can be readily detected by using this 2DE system. Thus the 50% reduction in expression of a protein expected in the event of a structural gene deletion is well within the level of detection. No significant quantitative decreases in protein expression that correlated with the recessive lethal mutations were detected, however.
Animals↗
Oligodendrocyte-derived J1-160/180 extracellular matrix glycoproteins are adhesive or repulsive depending on the partner cell type and time of interaction.
We have studied the functional involvement of J1-160 and J1-180 in the interaction between oligodendrocytes and neurons, astrocytes, or L cells in short- and long-term adhesion assays using monoclonal antibodies directed against topographically distinct epitopes on the molecules. Whereas antibodies to mouse liver membranes and monoclonal antibody 597 do not interfere with neuron-oligodendrocyte or astrocyte-oligodendrocyte adhesion after 30 min of coculture, antibodies 596, 619, and 620 interfere with astrocyte to oligodendrocyte and neuron to oligodendrocyte adhesion. The adhesion of L cells to oligodendrocytes is not affected by the antibodies. When neurons or astrocytes are cultured on oligodendrocytes for more than 30 min, monoclonal antibody 619 continues to reduce adhesion of astrocytes to oligodendrocytes after 1 and 2 h. However, during this time period the antibody affects neuron to oligodendrocyte adhesion in a different manner. It does not interfere with adhesion of neurons to oligodendrocytes at 1 h and enhances the adhesion of neurons to oligodendrocytes after 2 h of coculture. After 6 and 24 h of coculture, antibody 619 does not affect the adhesion of neurons or astrocytes to oligodendrocytes, suggesting that other adhesive mechanisms are predominant at later times of interaction. At all times studied, neurons and astrocytes adhered well to the oligodendrocytes. To study the influence of the J1 molecules on neuronal interactions in the absence of other oligodendrocyte-derived cell surface components, purified J1-160 was coated as a substrate and neuron attachment was measured as a function of time. Two hours after plating neurons adhered well to J1-160, as they did to laminin, while cell detachment was subsequently observed from J1-160, but not from laminin. These results implicate J1-160 and J1-180 in a recognition process between oligodendrocytes and neurons or astrocytes, but not fibroblasts. This recognition process appears to merge into adhesion or stabilization of cell contacts for astrocytes and destabilization of cell interactions or repulsion for neurons. It is likely that these two opposite effects in cell behavior elicited by the J1 molecules result from differential intracellular responses to a cell surface trigger possibly mediated by different cell surface receptors and/or different consequences in intracellular signaling networks.
Animals↗
Effects of dysphoria on maternal exchange dispositions.
Defining dysphoria as subclinical depression, we explored the extent to which maternal dysphoria influences the quality of relationships within the family and evaluated whether the effect of dysphoria on family relationships is selective or general and whether dysphoric effects on maternal behavior are similar or different when ratings of maternal behaviors are made by mothers versus observers. We expected that dysphoria would have general rather than selective effects on family relations rated by mothers and observers. In a sample of 40 American families at risk of child abuse or neglect, we found that maternal dysphoria did have significantly negative effects on mother-to-child and mother-to-parenting-partner relations, suggesting that maternal dysphoria has general rather than selective effects.
Child Abuse↗
Couples with an elderly parent with Alzheimer's disease: perceptions of familial relationships.
This study examined family relationships in families with and without an elderly parent with Alzheimer's disease. Spouses (29 pairs with an Alzheimer's diseased parent; 29 pairs with a healthy elderly parent) completed questionnaires regarding their perceived relationships with each other, their parent, and one of their own children (aged 8-18). In addition, they completed surveys that inquired about feelings of burden regarding the target parent. Couples perceived a poorer relationship with parents with Alzheimer's disease when contrasted to couples who had a healthy elderly parent. In addition, wives with an Alzheimer's parent also tended to have a more negative relationship with their husbands than wives who had a healthy parent. Perceptions of burden were associated with poorer spousal relationships for wives but not husbands.
Adaptation, Psychological↗
Nucleotide sequence analysis of a 10.5 kbp HindIII fragment of fowlpox virus: relatedness to the central portion of the vaccinia virus HindIII D region.
The nucleotide sequence of a 10465 bp HindIII genomic fragment from fowlpox virus (FPV) is presented. Analysis of the nucleotide sequence revealed 10 potential major open reading frames (ORFs). Five of these ORFs are predicted to encode polypeptides with significant homology to hypothetical polypeptides derived from nucleotide sequence analysis of the vaccinia virus (VV) HindIII D region. Interestingly, these homologous ORFs do not occur in the same tandem arrangement in the FPV genome as they do in the VV genome. These results are discussed.
Amino Acid Sequence↗
GABAergic growth cones: release of endogenous gamma-aminobutyric acid precedes the expression of synaptic vesicle antigens.
Growth cone fractions isolated from neonatal [postnatal day 3 (P3)] rat forebrain contain GABAergic growth cones as demonstrated by immunofluorescence staining with monospecific antibodies to gamma-aminobutyric acid (GABA). HPLC analysis shows that GABAergic growth cones release this endogenous GABA when stimulated with high K+. Endogenous GABA release is Ca2(+)-independent and, in this respect, similar to that seen previously with [3H]GABA. Isolated growth cone fractions also exhibit a K(+)-stimulated, Ca2(+)-independent release of endogenous taurine. None of the other amino acids shown to be present in isolated growth cone fractions were released, including glutamate, aspartate, and glycine. A population of dissociated cerebral cortical neurones prepared from P1 rat forebrain were GABA-immunoreactive after 1 day in culture. The cell body, neurites, and growth cones of these neurones were all stained with GABA antibodies. At this time in culture, neurones did not stain with either of two antibodies to synaptic vesicle antigens, i.e., p65 and synaptophysin. Growth cones isolated from P3 rat forebrain were also not immunoreactive with these antibodies. After about 8 days in culture, when neurones had established extensive networks of long, varicose axons and elaborately branched dendrites, many neurones and their neurites were immunoreactive for GABA antibodies. At this time in culture, p65 and synaptophysin antibodies did stain neuronal cell bodies and particularly their varicose axons. Dendrites were not stained with synaptic vesicle antibodies. These results suggest that GABAergic neurones synthesize GABA during neurite outgrowth and that GABA is present in, and can be released from, the growth cones of these neurones. The presence of GABA in GABAergic growth cones is not associated with synaptic vesicles, which explains the Ca2+ independency of both endogenous and [3H]GABA release from these growth cones.
Animals↗
Neonatal hypothyroidism: comparison of radioisotope and ultrasound imaging in 54 cases.
Fifty-four neonates with congenital hypothyroidism identified by the North East and North West Thames Regional hypothyroid screening programme between January 1985 and December 1987 were investigated with radioisotope (Tc99m) and ultrasound scans of the thyroid before treatment with 1-thyroxine was commenced. Compared with the radioisotope scans, ultrasound identified normally sited thyroid tissue in only 7 out of 10 cases, and ectopic thyroid tissue in only 5 out of 26 cases. Three out of 18 cases with no isotope uptake in the neck appeared to have normally sited tissue on ultrasound scan. We conclude that in our hands ultrasound of the neck is of only limited value in the assessment of young infants with congenital hypothyroidism.
Congenital Hypothyroidism↗
Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self-limiting genome replication.
The replication of the RNA genome of hepatitis delta virus is greatly facilitated by the presence of the only known virus-coded protein, the delta antigen. Most, if not all, infections are characterized by the presence of two electrophoretic forms of the delta antigen. These forms correspond to polypeptide lengths of 195 and 214 amino acids which are encoded by genomes with different nucleotide sequences. We used cDNA transfections to investigate the functions of these two forms of the delta antigen. We found that only the small form of delta antigen supported hepatitis delta virus genome replication and that the large form acted as a dominant negative repressor of such replication. This inhibition was potent. For example, the amount of genome replication was reduced eightfold when as little as 10% of the delta antigen was present as the large form. One interpretation of our results is that the delta antigen normally functions as part of a multimeric structure. In addition, our data suggest that synthesis of the large form, either during genome replication in cultured cells or even during infection in animals, may suppress delta replication, possibly leading to a self-limiting infection.
Animals↗
Specificities involved in the initiation of retroviral plus-strand DNA.
Reverse transcription of the retroviral RNA genome begins with tRNA-primed synthesis of a minus-strand DNA, which subsequently acts as the template for the synthesis of plus-strand DNA. This plus-strand DNA is initiated at a unique location and makes use of a purine-rich RNA oligonucleotide derived by RNase H action on the viral RNA. To determine the variables that are relevant to successful specific initiation of plus-strand DNA synthesis, we have used nucleic acid sequences from the genome of Rous sarcoma virus along with three different sources of RNase H: avian myeloblastosis virus DNA polymerase, murine leukemia virus DNA polymerase, and the RNase H of Escherichia coli. Our findings include evidence that specificity is controlled not only by the nucleic acid sequences but also by the RNase H. For example, while the avian reverse transcriptase efficiently and specifically initiates on the sequences of the avian retrovirus, the murine reverse transcriptase initiates specifically but at a location 4 bases upstream of the correct site.
Avian Myeloblastosis Virus↗
A specific base transition occurs on replicating hepatitis delta virus RNA.
Three independent lines of evidence showed that when an infectious clone of hepatitis delta virus of known sequence was used to initiate genome replication, up to 41% of the genomes were specifically mutated in the amber termination codon (UAG to UGG) for the open reading frame of the delta antigen, thereby increasing the length of the predicted protein from 195 to 214 amino acids. This change was detected only on molecules that participated in RNA-directed RNA synthesis.
Amino Acid Sequence↗
Newcastle disease virus fusion protein expressed in a fowlpox virus recombinant confers protection in chickens.
A cDNA copy of the RNA encoding the fusion (F) protein of Newcastle disease virus (NDV) strain Texas, a velogenic strain of NDV, was obtained and the sequence was determined. The 1,792-base-pair sequence encodes a protein of 553 amino acids which has essential features previously established for the F protein of virulent NDV strains. These include the presence of three strongly hydrophobic regions and pairs of dibasic amino acids in the pentapeptide Arg-Arg-Gln-Arg-Arg preceding the putative cleavage site. When inserted into a fowlpox virus vector, a glycosylated protein was expressed and presented on the surface of infected chicken embryo fibroblast cells. The F protein expressed by the recombinant fowlpox virus was cleaved into two polypeptides. When inoculated into susceptible birds by a variety of routes, an immunological response was induced. Ocular or oral administration of the recombinant fowlpox virus gave partial protection, whereas both intramuscular and wing-web routes of inoculation gave complete protection after a single inoculation.
Amino Acid Sequence↗
Coexpression by vaccinia virus recombinants of equine herpesvirus 1 glycoproteins gp13 and gp14 results in potentiated immunity.
The equine herpesvirus 1 glycoprotein 14 (EHV-1 gp14) gene was cloned, sequenced, and expressed by vaccinia virus recombinants. Recombinant virus vP613 elicited the production of EHV-1-neutralizing antibodies in guinea pigs and was effective in protecting hamsters from subsequent lethal EHV-1 challenge. Coexpression of EHV-1 gp14 in vaccinia virus recombinant vP634 along with EHV-1 gp13 (P. Guo, S. Goebel, S. Davis, M. E. Perkus, B. Languet, P. Desmettre, G. Allen, and E. Paoletti, J. Virol. 63:4189-4198, 1989) greatly enhanced the protective efficacy in the hamster challenge model over that obtained with single recombinants. The inoculum doses (log10) required for protection of 50% of hamsters were 6.1 (EHV-1 gp13), 5.2 (EHV-1 gp14), and less than 3.6 (vaccinia virus recombinant expressing both EHV-1 glycoproteins [gp13 and gp14]).
Amino Acid Sequence↗
Hepatitis delta virus genome replication: a polyadenylated mRNA for delta antigen.
Hepatitis delta virus (HDV) replicates its genome in the nucleus of an infected cell. However, an unsolved problem has been the identification in the cytoplasm of a putative mRNA for the synthesis of the only virus-coded protein, the delta antigen. We now report the characterization of an 800-base RNA that is cytoplasmic, polyadenylated, and antigenomic and that should direct the translation of the delta antigen. This RNA was about 500 times less abundant than full-length genomic RNA. We mapped the predominant 5' terminus and also the 3' site at which the poly(A) is added. At a point 15 to 20 bases upstream of the poly(A) addition site is the sequence AAUAAA, which could have been used as a signal for the polyadenylation. When an infectious cDNA clone of the whole HDV genome was changed at this site to UUUAAA, the clone was no longer infectious and it was unable to direct the synthesis of the delta antigen. These findings provided additional evidence that the polyadenylated RNA was at least the predominant method for the expression of the delta antigen. Apparently the HDV RNA was processed as if it were a host mRNA polymerase II transcript, although this did not necessarily indicate that HDV RNA was transcribed with this enzyme.
Antigens, Viral↗