Three polymorphisms at the D17S29 locus.
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Chromosome Mapping↗
Biomedical subjects
R Ray
Publications and source records attributed to R Ray.
1 alpha,25-dihydroxyvitamin D3-induced increments in hepatocyte cytosolic calcium and lysophosphatidylinositol: inhibition by pertussis toxin and 1 beta,25-dihydroxyvitamin D3.
1 alpha,25-Dihydroxyvitamin D3 rapidly increases cytosolic calcium and alters membrane phospholipid metabolism in hepatocytes. To define the causal relationship between these events, we examined the effects of 1 alpha,25-dihydroxyvitamin D3 on 32P-labeled lysophosphatidylinositol levels and cytosolic calcium as affected by pertussis toxin and 1 beta,25-dihydroxyvitamin D3, the biologically inactive analog. 32P-labeled lysophosphatidylinositol was determined by two-dimensional thin-layer chromatography. Cytosolic calcium was measured in cells loaded with quin-2AM. Within 5 min, 1 alpha,25-dihydroxyvitamin D3 increased hepatocyte cytosolic calcium by 31% (p less than 0.05) and 32P-labeled lysophosphatidylinositol by 38% (p less than 0.05). Pertussis toxin inhibited the hormone-induced rise in cytosolic calcium but not the increase in 32P-labeled lysophosphatidylinositol. Exposure to exogenous lysophosphatidylinositol for 5 min increased cytosolic calcium by 40% (p less than 0.05), an effect that was also inhibited by pertussis toxin. 1 beta,25-Dihydroxyvitamin D3 had no effect on either hepatocyte cytosolic calcium or 32P-labeled lysophosphatidylinositol but prevented the 1 alpha,25-dihydroxyvitamin D3-induced increments. The results suggest that a G protein sensitive to pertussis toxin is required for the transduction of the lysophosphatidylinositol signal but not the generation of the signal. The ability of 1 beta,25-dihydroxyvitamin D3 to inhibit the 1 alpha,25-dihydroxyvitamin D3-induced changes in phospholipids suggests that the epimer may compete with 1 alpha,25-dihydroxyvitamin D3 for an initiating receptor.
Animals↗
Molecular cloning and sequence analysis of the fusion glycoprotein gene of human parainfluenza virus type 2.
A cDNA clone containing a 2.0-kb insert was identified as the human parainfluenza virus type 2 (PI2) fusion glycoprotein gene by hybridizing with a viral RNA probe and a synthetic oligonucleotide derived from a conserved sequence found in other paramyxovirus fusion protein genes. The complete nucleotide sequence of the glycoprotein gene was determined by the dideoxynucleotide sequencing procedure and found to contain a single, large open reading frame encoding a protein of 551 amino acids with a calculated molecular weight of 59,664. Comparison of the P12 fusion protein with those of other paramyxoviruses indicated similarities in overall length, N-terminal signal peptide sequence (amino acids 7 to 25), C-terminal membrane-spanning region (amino acids 486 to 513), and a highly conserved fusion sequence region at the N-terminus of the F1 subunit (amino acids 107 to 132).
Amino Acid Sequence↗
Sequence of the hemagglutinin-neuraminidase gene of human parainfluenza virus type 1.
The nucleotide sequence of the gene encoding the hemagglutinin-neuraminidase (HN) glycoprotein of human parainfluenza virus type 1 (PI1) was determined from cDNA clones derived from poly(A)+ RNA extracted from infected cells. A single open reading frame in the sequence was found to encode a putative protein of 575 amino acids with a calculated molecular weight of 63,960. The predicted amino acid sequence contains ten potential sites for N-linked glycosylation and one major hydrophobic region located 35 amino acids from the amino terminus, which appears to be the signal-anchor domain of HN. Comparison of the amino acid sequence with the HN glycoproteins of other paramyxoviruses indicated that the PI1 HN protein is most closely related to the Sendai virus (SV) HN protein.
Amino Acid Sequence↗
Human parainfluenza virus induces a type-specific protective immune response.
Induction of type-specific and cross-protective immune responses against human parainfluenza viruses have been investigated. The envelope glycoproteins HN (76 kDa) and F0 (62 kDa) from parainfluenza type 2 virus were selectively solubilized with octylglucoside. Detergent-soluble envelope glycoproteins were used as vaccine antigens for intranasal immunization of hamsters. The immunized animals showed complete protection from challenge infection with prototype live virus but failed to demonstrate a significant level of protection against either human parainfluenza type 1 or type 3 virus. The sera and bronchial lavages of immunized animals also showed type-specific neutralizing antibodies. A similar type-specific protective immune response was also noted after primary infection with live virus. The results indicate that a multivalent parainfluenza virus vaccine is probably required for protection against natural infection.
Animals↗
Oncogenes, malignant transformation, and modern medicine.
During the past decade there have been remarkable strides in the understanding of the basic mechanism of cancer. It is now clear that there is a set of genes, known as oncogenes, that can cause cells to become malignant if their expression is altered, either by mutation or overexpression. The products of these genes include growth factors, growth factor receptors, signal tranduction proteins, and DNA binding proteins. The normal cellular counterparts of these genes play very important roles in the regulation of growth and proliferation by normal cells. Another set of genes, anti-oncogenes, also play an important role in preventing abnormal cell proliferation. The remarkable explosion of understanding of the pathophysiology of malignancy has led to a common unifying concept of malignant transformation that applies to all tumors. It is likely that these new insights will lead to improved and more specific treatments for malignant disease in the next decade.
Animals↗
Mithramycin selectively inhibits the transcriptional activity of a transfected human c-myc gene.
The G-C specific DNA binding drug mithramycin selectively inhibits expression of the c-myc gene in a number of cell types. We have tested the ability of this agent to inhibit the expression of a transfected human c-myc gene in a murine fibroblast cell line. Expression of c-myc is inhibited in the first 24 hours of mithramycin exposure (in contrast to actin gene expression, which is unaffected). Nuclear runon transcription of c-myc by nuclei isolated from mithramycin treated cells is decreased, indicating inhibition of transcription initiation. However, treatment of isolated nuclei with mithramycin also results in decreased c-myc transcription. Thus, inhibition of c-myc expression by mithramycin in these cells appears to occur at the transcriptional level and is most likely mediated at both the transcription initiation and elongation level. This suggests that mithramycin selectively interacts with the G-C rich c-myc promoter, preventing formation of the c-myc transcription initiation complex.
Animals↗
Tort reform recommendations for West Virginia.
Tort reform is central to resolution of the malpractice issue in West Virginia. This article examines tort law and malpractice as viewed from federal and state levels and compares general liability costs in states. The article also looks at national trends in malpractice awards; at state initiatives in tort reform; and finally extracts what works and what doesn't. It presents strategies for legislative approaches to tort reform.
Insurance, Liability↗
Can we prevent the increasing prevalence of cataract among the elderly?
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Aged↗
Evaluation of care of the elderly in the Senior Citizens' Health Care Centre.
In an effort to expand the community based services for the elderly, the Senior Citizens' Health Care Centre (SCHCC) was developed in 1986, with the support of the Ministry of Health providing the policy direction and staff, and the Home Nursing Foundation bearing some of the operating expenditure. The first 171 clients with impaired physical functions who attended the centre for day care and rehabilitation were studied. They were exposed to a programme package inclusive of health and social areas. Specific areas covered were Activities of Daily Living (ADL), simple mental status examination and use of mobility aids. The average duration of treatment at the centre required by the 95 day care clients was 84 days or 20 visits, while the 76 rehabilitation clients required 71 days or 13 visits. The 68.4% of the clients who completed their treatment at the centre successfully, reached the goals towards independence set for them well within 3 months of their admission into the centre. This was noted when scores were compared at admission and discharge. Due to various reasons, 31.6% did not complete the treatment. This study shows how the elderly with physical impairments may benefit from the programmes in the SCHCC.
Activities of Daily Living↗
Rapid actions of 1 alpha,25-dihydroxyvitamin D3 on Ca2+ and phospholipids in isolated rat liver nuclei.
The effects of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) on Ca2+ levels and phospholipid metabolism were studied in isolated nuclei prepared from rat liver. Nuclear Ca2+ concentration was estimated with the fluorescent indicator Fura 2. In agreement with previous reports, ATP (1 mM) produced a rapid increase in nuclear Ca2+ from 188 +/- 25 to 593 +/- 121 nM. Exposure to 1 alpha,25-(OH)2D3 (20 nM) also produced a rapid increase in nuclear Ca2+ to 402 +/- 71 nM. The 1 beta epimer of 1 alpha,25-(OH)2D3 had no effect. Nuclear phosphatidylinositol was labeled by incubation with [gamma-32P]ATP for 3 h. 1 alpha,25-(OH)2D3 produced a two-fold increase in [32P]lysophosphatidylinositol (LPI) within 5 min from 44 +/- 11 to 87 +/- 19 cpm/2.5 x 10(7) nuclei. 1 beta,25-(OH)2D3 had no effect on [32P]LPI production. Exposure of nuclei to exogenous LPI (15 microM) produced an instantaneous increase in nuclear Ca2+ to 372 +/- 81 nM, comparable to ATP and 1 alpha,25-(OH)2D3. The rapid effects of 1 alpha,25-(OH)2D3 on phospholipid metabolism and Ca2+ in isolated nuclei suggest that the steroid may exert effects distinct from the well-characterized receptor-mediated changes in gene expression.
Adenosine Triphosphate↗
Target cell metabolism of 1,25-dihydroxyvitamin D3 to calcitroic acid. Evidence for a pathway in kidney and bone involving 24-oxidation.
1,25-dihydroxyvitamin D3 is converted to calcitroic acid before being excreted in the bile. Biosynthesis of calcitroic acid has been demonstrated in two target cells of vitamin D, in the kidney and the osteoblastic cell line UMR-106. Calcitroic acid was identified by combinations of h.p.l.c., u.v. spectroscopy and mass spectrometry. Evidence is presented that calcitroate is derived from the 24-oxidation pathway, possibly through the intermediate 24,25,26,27-tetranor-1,23-dihydroxyvitamin D3. The 24-oxidation pathway to calcitroic acid in bone cells is stimulated by 1,25-dihydroxyvitamin D3. The pathway in both bone cells and perfused kidney operates at physiological concentrations of substrate and appears to be capable of rapid clearance of the hormone.
Animals↗
Immune responses to influenza virus in orally and systemically immunized mice.
In our studies on the induction of an immune response by oral immunization, we have explored the potential of a novel approach for antigen delivery by microencapsulation. This procedure preserved the immunogenicity of the influenza virus introduced by either systemic or oral routes. Furthermore, the levels of specific antibodies in serum and in saliva were enhanced and lasted longer (up to 4 months) in animals immunized with of antigens in microencapsulated form than in animals immunized with equal doses of free suspension. Preliminary challenge experiments showed a correlation between levels of antibodies and protection. All mice systemically immunized were protected against the virus, while mice orally immunized with lower doses of microencapsulated antigen had better survival rates than those immunized with higher doses. Additional experiments suggested that low doses of immunogen were able to generate better protective immunity than high doses, which may instead be tolerogenic. Further experiments with a well characterized microencapsulated antigen (size of microcapsules, time of release of antigen, as well as its dose and form) will be necessary to establish conditions for optimal immunization protocols applicable for the oral or systemic routes.
Administration, Oral↗
The behavioural and welfare implications of housing demand under rationing. The United Kingdom experience.
"The present study investigates, on pooled budget data (1968/1985) from United Kingdom Family Expenditure Surveys, the consequences of relaxing the assumption of free choice in housing, while continuing to maintain the assumption of unrationed demand for other items. Since the demand equations are estimated jointly as a system, introducing rationed demand for one item will have consequences for the other demand equations. We investigate the nature and magnitude of such changes using the framework of a general demographic demand system that allows for non-linear/non-separable commodity demand behaviour and also permits the equivalence scales to vary between the rationed and unrationed items." The author finds that "unlike in previous studies, the rationed demand system fails to reject linear preferences."
Demography↗
Expression of the fusion glycoprotein of human parainfluenza type 3 virus in insect cells by a recombinant baculovirus and analysis of its immunogenic property.
The fusion (F) glycoprotein of human parainfluenza type 3 (PI3) virus was produced in insect cells using a baculovirus expression vector (pAcYM1). The recombinant glycoprotein was identified by its reactivity with specific monoclonal and polyclonal antibodies and showed an apparent molecular mass of 70 kDa. Although the fusion protein was found on the infected cell surface, it did not appear to be proteolytically cleaved to F1 and F2 subunits. Immunization of hamsters with the recombinant protein elicited antibody which neutralized infectivity and blocked fusion of virus-infected cells. The protective response to challenge infection of immunized hamsters was similar to that observed with affinity purified F from PI3 virus (Ray et al., J. Virol. 62, 783-787, 1988).
Animals↗
Alcoholism--assessment and diagnosis.
Ninety-two patients with alcoholism were interviewed on various aspects of alcohol use. Factor analysis of the data revealed five factors: withdrawal symptoms; help seeking behaviour; pathological drinking; legal difficulties; family problems. The analysis suggested the possibility of heterogenity in this clinical sampling with alcoholism.
Alcohol Drinking↗
Mithramycin blocks protein binding and function of the SV40 early promoter.
Specific interactions between DNA and transcription factors are necessary for transcription initiation. These interactions provide a potential target for the selective inhibition of eukaryotic gene expression. Mithramycin is a DNA binding antibiotic which, in the presence of Mg2+, binds G-C containing sequences in the minor groove. The SV40 early promoter contains six G-C decanucleotide sequences, which are binding sites for the transcriptional activating factor, Sp1. Each of the six Sp1 binding sites of this promoter is protected from DNAse 1 digestion by mithramycin binding. Mithramycin binding to the G-C rich sequences in the SV40 early promoter prevents subsequent protein binding to these sequences. The gel retardation of the SV40 early promoter fragment incubated with a HeLa cell extract is completely abrogated by pretreatment of the DNA fragment with mithramycin. The functional significance of mithramycin binding is reflected in the ability of mithramycin to block promoter function. Mithramycin inhibits promoter dependent transcription in an in vitro runoff transcription system in a concentration dependent manner. This suggests that mithramycin prevents transcriptional activation of the SV40 early promoter by blocking binding of transcriptional activating proteins to G-C rich promoter regions.
Base Sequence↗
Adult-onset chorea and dementia with propionic acidemia.
Propionic acidemia usually presents in the newborn period with severe metabolic acidosis and lethargy. A 31-year-old man with adult onset chorea and dementia had propionic acidemia due to propionyl CoA carboxylase deficiency. Metabolic investigations may prove useful in patients with movement disorder of unknown etiology.
Adult↗