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Biomedical subjects

N Roy

Publications and source records attributed to N Roy.

At least 73 records · Page 4Linked to original sources
PubMed1994

Activation of Ito cells involves regulation of AP-1 binding proteins and induction of type I collagen gene expression.

Activation of liver Ito cells is characterized by increased proliferation, fibrogenesis, loss of cellular retinoid and change of cell-shape. Here, we have described fundamental differences between freshly isolated Ito cells (FIC) and long-term cultured Ito cells (LTIC). This process of activation correlates with the absence of expression of Pro alpha 1(I) gene in FIC. LTIC expressed abundant transcripts of Pro alpha 1(I) gene. Nuclear run-off experiments showed the inability of FIC to support Pro alpha 1(I) RNA transcription while LTIC transcribed it greater than 5-fold as compared with FIC. Transforming growth factor beta (TGF beta)-treated LTIC had a preferential increase in the rate of Pro alpha 1(I) gene transcription as compared with control LTIC. A human collagen type I promoter-enhancer construct (pCOL-KT) [Thompson, Simkevich, Holness, Kang and Raghow (1991) J. Biol. Chem. 266, 2549-2556] was readily expressed in LTIC but failed to be expressed in FIC. Furthermore, TGF beta treatment of LTIC resulted in an increased expression of pCOL-KT. The deletion of an activator protein-1 (AP-1) binding site (+598 to +604) in the 360 bp enhancer region of pCOL-KT (S360) caused decreased expression of the CAT reporter gene, suggesting that this bonafide AP-1 site can, at least in part, mediate the transactivation effect of TGF beta. Using DNAase I protection, we demonstrate a single foot-print located at +590 to +625 in the S360 fragment; nuclear extracts prepared from TGF beta-treated LTIC exhibited greater activity of these AP-1 binding proteins. Gel mobility assays corroborated and extended the footprinting observation. No AP-1-binding activity was found in the nuclear extracts of FIC. Double-stranded oligonucleotides containing the consensus AP-1 motif were able to compete out the binding; consensus NF-1 motif oligonucleotides failed to do so. The preincubation of nuclear extracts from control and TGF beta-treated LTIC with antibodies against c-jun and c-fos rendered a reduced binding of AP-1 proteins to the target S360 fragment.

Animals↗
PubMed1994

Two 5q13 simple tandem repeat loci are in linkage disequilibrium with type 1 spinal muscular atrophy.

The gene for the common recessive neuromuscular disorder spinal muscular atrophy (SMA) has been previously mapped to chromosome 5q. We report here linkage disequilibrium analyses of two polymorphic simple tandem repeat (STR) sequences which map into the critical region of 5q13 containing the SMA gene. The polymorphisms presented are constituents of CATT-1, a complex STR which is present in as many as four or more copies per chromosome 5. The PCR can amplify as many as eight CATT-1 products of different sizes from genomic DNA samples due to differing numbers of CA dinucleotides at each STR location (sublocus). Oligonucleotide primers for two of these subloci have been developed for specific PCR assays; a variety of allele sizes can be generated with each assay and, in some cases, no amplification products are detected due to null alleles. The genotyping of 149 SMA Type 1 chromosomes and 142 normal chromosomes from Canadian and American kindreds reveals the presence of significant linkage disequilibrium between the null allele of the sublocus referred to as CATT-40G1 and mutation(s) causing SMA Type 1 (Werdnig-Hoffmann disease). Allele 2 of the second sublocus, CATT-192F7, is also in linkage disequilibrium with SMA Type 1 although the degree of this association is less than that found for CATT-40G1. The proximal and distal STRs from the critical region, D5S435 and D5S351, showed no linkage disequilibrium with SMA. The data presented here will serve as a framework for future linkage disequilibrium analyses, expediting the final stage of the search for the SMA gene.

Alleles↗
PubMed1994

Effects of sleep deprivation and sleep fragmentation on upper airway collapsibility in normal subjects.

Sleep deprivation can induce or worsen nocturnal respiratory disturbances. In patients with sleep apnea hypopnea, sleep abnormalities consist of repetitive episodes of arousals and awakenings that lead to sleep fragmentation. Because the propensity for upper airway collapse is increased in these patients, we wondered if sleep fragmentation could increase upper airway collapsibility and contribute to the pathogenesis of this disease. In eight normal subjects, upper airway collapsibility was assessed during sleep by progressively decreasing the pressure in a nasal mask while recording airflow, mask, and esophageal pressures. The critical pressure was determined by the relationship between breath-by-breath values of maximal inspiratory airflow of each flow-limited inspiratory cycle and the corresponding mask pressure. Critical pressure was measured twice in each subject: after one night of total sleep deprivation and after one night of sleep fragmentation using auditory stimuli. The two measures were done in random order 1 wk apart. A polysomnographic recording was obtained the night after each measurement of critical pressure. Sleep architecture was identical after sleep deprivation and fragmentation. Sleep-related breathing abnormalities were more frequent after sleep fragmentation than after sleep deprivation. Critical pressure was -17.1 +/- 6.8 cm H2O (mean +/- SEM) after sleep deprivation, and -12.3 +/- 6.3 cm H2O after sleep fragmentation (p < 0.05), corresponding to an earlier closing of the upper airway. We conclude that sleep fragmentation leads to a higher upper airway collapsibility than does sleep deprivation.

Adult↗
PubMed1994

Ventricular dysphonia following long-term endotracheal intubation: a case study.

Although dysphonia following long-term endotracheal intubation (EI) is a common complication, no cases of ventricular dysphonia have been reported. This investigation reports a case of persistent ventricular dysphonia following a 12-day intubation period. The patient received eight sessions of voice therapy employing the manual, laryngeal musculoskeletal tension reduction procedure. Improvements in perceptual, acoustic, and videolaryngoendoscopic measures of voice production are reported. Mechanisms contributing to the development, maintenance, and resolution of ventricular dysphonia are discussed.

Humans↗
PubMed1993

Genetic linkage analysis of Canadian spinal muscular atrophy kindreds using flanking microsatellite 5q13 polymorphisms.

The spinal muscular atrophies (SMA) are among the most common autosomal recessive disorders. We have performed linkage analysis using both standard restriction fragment length polymorphisms (RFLPs) as well as microsatellite polymorphisms [Ca(n)] on 49 Canadian SMA families (types 1, 2, and 3) that both flank and are linked to SMA. The closest SMA linkage was observed with the MAP1B locus (zmax = 8.04, theta max = 0.0). Multipoint linkage analysis gave a high probability of SMA mapping between D5S6 and D5S39. Only one family (type 3) that fulfilled our diagnostic criteria for SMA showed nonlinkage with 5q13 markers. This study shows the feasibility of accurate molecular diagnosis of SMA utilizing 5q13 satellite polymorphisms.

Canada↗
PubMed1993

Effects of the manual laryngeal musculoskeletal tension reduction technique as a treatment for functional voice disorders: perceptual and acoustic measures.

During a 2-year period, 17 patients with "functional dysphonia" were assessed and managed in a hospital setting. A single treatment approach, known as manual laryngeal musculoskeletal tension reduction, was employed. The effects of the therapy regimen were analyzed using perceptual and acoustical measures of vocal function. The results indicated a significant change in the direction of "normal" vocal function in the majority of patients within one treatment session. Perceptual measures of severity were consistently more likely to be rated as normal following treatment. Acoustic measures of voice confirmed significant improvements in jitter, shimmer, and signal-to-noise ratio (SNR). Results are discussed in terms of the clinical utility and effectiveness of this treatment approach for functional dysphonia.

Adult↗
PubMed1993

Immunomodulation and 'Ia' variability in dendritic lymph cells: a radiobinding immunoassay versus immune response study.

A radiobinding immunoassay technique has been employed to determine the 'Ia' antigens localised on the surface of the following immunocompetent cells: Dendritic lymph cells from peripheral intestinal lymph, peritoneal macrophages and thymocytes all gathered from sheep red blood cell treated animals, and the irradiated cell controls. A corresponding popliteal lymph node assay was performed following the administration of the same cells into the foot pad of allogeneic rats to determine the comparative immunogenic responsiveness. Dendritic lymph cells in free flowing lymph of sensitised, irradiated and control animals showed a significantly higher 'Ia' content and consequently greater immunogenicity as measured by the popliteal lymph node assay. Sheep red blood administration in animals may stimulate surface 'Ia' expression in lymph derived dendritic cells resulting in higher immune-responsiveness.

Animals↗
PubMed1992

5' untranslated sequences modulate rapid mRNA degradation mediated by 3' AU-rich element in v-/c-fos recombinants.

One major determinant of rapid mRNA decay is the presence of AU-rich sequences located in 3' untranslated regions (UTR). To assess for the contribution of upstream sequences on the activity of the 3' AU-rich destabilizing element, we have determined the decay-rates of v-/c-fos hybrid transcripts by quantitative RNA protection analysis. In a transient expression assay, v-/c-fos recombinants generated two mRNA populations via alternative splicing and removal of an optional intron entirely located in the 5' UTR. Both mRNA species were found to be relatively stable in constructs lacking the c-fos AU-rich destabilizing element. Unexpectedly, in recombinants where intrinsic AU sequences were kept intact, only the full-length mRNA population showed high instability whereas the spliced mRNA species remained relatively stable. A v-/c-fos 5' UTR fragment encoding the optional intron was inserted into alpha-globin genes harboring either the c-fos or GM-CSF destabilizing element. The splicing and degradation patterns of these heterologous transcripts paralleled that of v-/c-fos recombinants. These observations unmasked a 5' cis-acting element in v-/c-fos mRNA whose presence is required for the activity of the AU-rich destabilizing element. They demonstrate the important role of interactions between distinct sequences on the regulation of mRNA stability.

3T3 Cells↗
PubMed1991

A frameshift mutation at the NH2 terminus of the nucleoprotein gene does not affect generation of cytotoxic T lymphocyte epitopes.

BALB/3T3 cells infected with a retroviral vector encoding the influenza virus nucleoprotein (NP) gene are efficiently lysed by CTL generated in BALB/c mice (H-2d background). Cells transduced with a mutant form of NP which contains a frameshift mutation at its NH2 terminus (NPm) do not express biochemically detectable levels of protein but nevertheless present Ag to CTL with high efficiency. Cold target inhibition studies indicate that the same CTL epitope(s) are recognized in cells harboring NP or NPm. L929 cells transduced with the NPm gene also present Ag efficiently to CTL raised in C3H mice (H-2k background). Cells engineered to express 5- to 15-fold lower levels of wild-type NP were not capable of presenting Ag to CTL, arguing against the notion that CTL are able to lyse cells expressing very low levels of Ag which might have resulted from suppression of the frameshift mutation in NPm. Implications to the mechanism of epitope generation in class I MHC-restricted immune responses are considered.

Animals↗
PubMed1991

Procedure for Obtaining Efficient Root Nodulation of a Pea Cultivar by a Desired Rhizobium Strain and Preempting Nodulation by Other Strains.

The specificity between the sym-2 gene bred into certain cultivars of pea (Pisum sativum L.) and the nodX gene, present only rarely in isolates of Rhizobium leguminosarum, can be exploited to preempt competition or nodulation blocking by a Rhizobium strain indigenous to a soil environment. The principle is to isolate an R. leguminosarum strain prevalent in a locale, convert it into a strain that will nodulate a desirable pea cultivar carrying sym-2 by establishing nodX in it, and then use the resulting Rhizobium strain with the pea cultivar carrying sym-2. To accomplish this, we first constructed a transposon Tn5 derivative called Tn5nodX and an efficient delivery vehicle that is suicidal in R. leguminosarum. We tested the potential utility of the system in greenhouse experiments. The results are encouraging enough to warrant extensive experiments under field conditions.

Journal Article↗
PubMed1990

Synthesis of disaccharide methyl glycosides related to the polysaccharide from Klebsiella serotype 40 and a study of their inhibition in the precipitin reaction.

The methyl glycosides of alpha-D-Manp-(1----4)-alpha-L-Rhap (3), alpha-L-Rhap-(1----3)-beta-D-Galp (4), beta-L-Rhap-(1----3)-beta-D-Galp (5), beta-D-Galp-(1----2)-alpha-L-Rhap (6), and beta-D-GlcpA-(1----2)-alpha-L-Rhap (7) have been synthesised and their inhibition reactions in the Klebsiella serotype 40 immune system have been studied. The results obtained accord with only one of two structures proposed for the repeating unit of the K40 antigen.

Carbohydrate Sequence↗