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Biomedical subjects

R Ray

Publications and source records attributed to R Ray.

At least 199 records · Page 11Linked to original sources

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↗

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↗

Work profiles of research statisticians.

Analysis of work profiles of 138 persons who had published in the Journal of the American Statistical Association showed this study group published more often than 128 members of the Association and tended to enjoy research, being less interested in the theoretical contribution of their work and more interested in the likelihood of work being published. Administrative and committee duties were impediments for those who published.

Attitude↗

Health and morbidity profiles of older adults in Singapore and their health care needs.

Before setting up the first Senior Citizens' Health Care Centre (SCHCC), a survey was done to establish the health and morbidity profiles of older adults in the community and their health care needs. Community volunteers personally interviewed 1,697 persons aged 55 years and above, living in three areas in Singapore. The response rate was 75%. The respondents' general characteristics, the prevalence rate of chronic diseases, their functional and mobility status, utilisation of the health services and how the chronic diseases affected their activities of daily living (ADL) were studied. Among the respondents, 2.1% required nursing care, 4.2% were unable to climb stairs, and 23.3% were on long-term medications. As compared to the younger age groups, those 75 years and above reported more difficulties with mobility (semi-ambulant 6.5%, bedridden 1.8%), more needed assistance in ADL (bathing 4.8%, toiletting 4.7%, dressing 3.0%, and feeding 2.4%) and a higher percentage required nursing care (3.6%). Services that would benefit the frail elderly are reported in this paper.

Activities of Daily Living↗

Mouse fibroblasts transformed with the human c-myc gene express a high level of mRNA but a low level of c-myc protein and are non-tumorigenic in nude mice.

Overexpression of a transfected c-myc gene under the control of a strong promoter causes the phenotypic changes of malignant transformation. We have investigated the effect of exogenous c-myc gene expression in NIH3T3 cells transfected with an intact human c-myc gene which is expressed under the control of its own promoter. The presence of the exogenous c-myc gene in the transfected cells was documented by Southern blot analysis. The transfected clones contained 20-40 copies of the human c-myc gene and demonstrated a proportional elevation in the level of c-myc mRNA which had a normal half life of 20-30 min. Despite the high level of c-myc mRNA, the transfected cells contained a relatively low level of c-myc protein and expression appears to be regulated at a post-transcriptional level. The transfected cells exhibited a decreased serum requirement for growth and formed colonies in soft agar, but were non-tumorigenic in Balb/c athymic nude mice. The morphologic evidence of transformation in the absence of tumorigenesis suggests that transfection of murine fibroblasts with multiple copies of the c-myc gene expressed under the control of its own promoter may cause partial transformation.

Animals↗

Specific soman-hydrolyzing enzyme activity in a clonal neuronal cell culture.

An enzymatic activity that specifically hydrolyzes the highly toxic organophosphorus anticholinesterase compound soman (pinacolyl methylphosphonofluoridate) has been identified and partially characterized in the clonal neuronal neuroblastoma-glioma hybrid NG108-15 cell line. Using the whole cell homogenate as the enzyme source and 1 mM substrate, the relative rate of hydrolysis of two other toxic anticholinesterase compounds sarin (isopropyl methylphosphonofluoridate) and tabun (ethyl-N-dimethyl phosphoramidocyanidate) is approximately one-tenth the rate of hydrolysis of soman, while DFP (diisopropyl phosphorofluoridate), paraoxon (p-nitrophenyl diethylphosphate), and a phosphinate PNMPP (p-nitrophenyl methyl (phenyl) phosphinate) are not hydrolyzed. Analysis of the kinetics of soman hydrolysis reveals two components of the enzyme activity with different affinities and reaction rates. Unlike previously reported enzymes of this type, this enzyme lacks chiral specificity and thus hydrolyzes both toxic and non-toxic soman stereoisomers at equal rates. The enzyme activity is stable at low temperature, found almost exclusively in the soluble fraction of these cells, and enhanced significantly by Mn2+ and by chemical differentiation of these cells in culture. The results suggest possible application of this enzyme for soman detection and/or detoxication, and use of the NG108-15 cell line to study the natural function(s) of enzymes of this type.

Animals↗