SEARCH · PubMed Health

Results for “insulators”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources

PubMed1997

The activity of the scs and scs' insulator elements is not dependent on chromosomal context.

Sequence elements that protect a reporter gene from chromosomal position effects or that block enhancer-activated transcription are called insulators. Using a plasmid-based microinjection assay with Xenopus laevis oocytes, we show that the heterologous Drosophila melanogaster scs and scs' insulator elements do not require chromosomal context to block enhancer-activated transcription. A single insulator element partially blocks enhancer-activated transcription, indicating that each element operates independently rather than as part of a pair. Deletion analysis of the 1.8-kb scs element identified a 220-bp fragment from one of the DNase I-hypersensitive regions that has full blocking activity in the oocyte assay. This fragment corresponds to the critical region of the scs mapped in previous studies with Drosophila. A time course of transcription shows that the scs blocks enhancer-activated transcription as early as transcription can be detected, about 30 min after injection. Complete assembly of the DNA template into nucleosomes requires 4 h. The scs and scs' sequences do not block site-specific recombination by FLP recombinase, implying that insulators do not operate by a general mechanism that physically sequesters the DNA. These data are most consistent with a model for insulator action in which direct interaction between the insulator and either the enhancer or promoter confers directionality to enhancer-activated transcription.

Animals↗

PubMed1981

Passive transfer of insulitis from the "BB" rat to the nude mouse.

The "BB" rat spontaneously develops insulitis, and an insulin-dependent diabetic syndrome like that in man. Lymphocytes were isolated from blood and spleen of newly-detected "BB" diabetic rats and injected intraperitoneally (IP) into athymic nude mice. Of 72 mice receiving single injections 37% showed insulitis, with 13% of islets examined being affected, and mean intensity of 1.9 +/- 0.3 (on a scale of 0 to 3). In 12 mice receiving 3 separate injections of pooled blood and spleen lymphocytes, 58% showed insulitis, with 17% of islets affected, and mean intensity 2.5 +/- 0.3. Of 45 control mice either untreated, injected IP with saline, or injected with cells from nondiabetic control rats, only one showed mild insulitis. No random or post IP glucose hyperglycemia was observed. Thus, 1) passive transfer of insulitis has been achieved; 2) insulitis may be present without glucoregulatory disturbances; 3) the pancreatic B cell need not display abnormal membrane structure for it to be susceptible to involvement in the cell-mediated immune process; and 4) detailed studies are required to define the relationship of administered lymphocytes to the observed pathology.

Animals↗

PubMed2004

Threshold current for an insulated epidural needle in pediatric patients.

We designed this study to determine the threshold current for nerve stimulation of an insulated needle in the epidural space. The intended dermatome was identified using the bony landmarks of the spine. An 18-gauge insulated Tuohy needle was inserted perpendicularly to the skin and advanced until "loss of resistance" was felt. A nerve stimulator was then connected to the insulated needle. Twenty patients were studied using an insulated Tuohy needle and one patient was studied using a noninsulated Tuohy needle. Muscle twitch was elicited with a current of 11.1 +/- 3.1 mA (mean +/- sd) in all patients in which an insulated needle was used. Muscle twitches were within 2 myotomes of the intended level (based on bony landmarks). Muscle twitch was not elicited with a noninsulated needle. After catheter threading, positive stimulation tests were elicited via epidural catheters in all patients (4.9 +/- 2.3 mA). Postoperative radiograph confirmed all catheter placements within 2 myotomes of the muscle twitches. Electrical stimulation may be a useful adjuvant tool to loss of resistance for confirming proper thoracic epidural needle placement. The threshold current criteria for an insulated needle (6-17 mA) would be higher than the original Tsui test criteria described for an epidural catheter (1-10 mA) in the epidural space.

Adolescent↗

PubMed1985

Genetic analysis for insulitis in NOD mice.

Non-obese diabetic (NOD) mice spontaneously develop diabetic signs akin to those of Type I diabetes in man. Insulitis, i.e., lymphocytic infiltration around and into the pancreatic islets is one of the characteristics of such mice. It is also the etiologic pathological lesion in the development of diabetes mellitus in NOD mice. Thus, we chose insulitis as a marker for genetic analysis of the development of diabetes mellitus in NOD mice and clarified the mode of its inheritance. In breeding studies between NOD and C57BL/6J mice, insulitis was not observed in the F1 and (F1 X C57BL/6J) backcross generations, but was found with incidences of 3.9% in females and 1.4% in males in the F2 generation and 23.7% in females and 12.1% in males in the (F1 X NOD) backcross generation. These incidences in the F2 and (F1 X NOD) backcross females corresponded approximately to 1/16 and 1/4 of the incidences of 89.7% in the NOD females, respectively. A similar relationship was observed between the F2 and (F1 X NOD) backcross males and the NOD males. When the gene expressivity of both sexes for a double recessive homozygote was assumed to be the incidences of insulitis in 9-week-old NOD females and males, respectively, the expected numbers of both sexes with and without insulitis in the F2 and backcross generations agreed well with the observed ones. These observations suggest that two recessive genes on independent autosomal chromosomes are necessary for the development of insulitis in NOD mice.

Animals↗

PubMed1989

Studies on the thermal insulation effect of the Korean women's folk clothes.

The purpose of this study is to examine the basic data useful for more comfortable folk clothes of Korean women, with respect to their thermal insulation effect. The result of this study is summarized as follows, by comparing the calculated thermal insulation effect of Korean women's folk clothes with that of the western style clothes. 1. The thermal insulation effect of the Korean women's folk clothes showed that summer clothes accounted for 0.67-0.93 Clo, while spring and autumn clothes showed 1.09-1.20 Clo. 2. Air layer had more effect on the thermal insulation of the Korean women's folk clothes than one of their material properties. 3. The thermal insulation of the Korean women's folk clothes features higher effect in the lower part of the body as compared with one the western style clothes, which act as an important factor in the thermal insulation.

Adult↗

PubMed1990

Studies on autoimmunity for initiation of beta-cell destruction. VI. Macrophages essential for development of beta-cell-specific cytotoxic effectors and insulitis in NOD mice.

NOD mice were treated with silica (which is selectively toxic to macrophages) from 4 or 20.5 wk of age. Syngeneic neonatal pancreases were transplanted into the renal subcapsular space of the NOD mice at 21 wk of age. Silica treatment was continued until 24 wk of age, and then the mice were killed for examination of islet morphology. Neither the islets in transplanted pancreases nor the host pancreatic islets from the early long-term silica-treated animals revealed insulitis. In contrast, most of the islets in transplanted pancreases from the late short-term silica-treated animals showed severe insulitis and beta-cell necrosis, as did the host islets. A further experiment was performed to compare the effect of late short-term silica treatment with that of anti-L3T4-antibody treatment of the same time and duration. In contrast to the late short-term silica-treated animals, the transplanted pancreases in the anti-L3T4-antibody-treated animals revealed intact islets, although most of the host islets showed insulitis. The control group, which received no treatment but did receive neonatal pancreases, revealed severe insulitis and beta-cell necrosis of both transplanted and host islets. These results suggest that early macrophage depletion can abolish the development of beta-cell-specific immunologic effectors but that late macrophage depletion, after the development of insulitis, does not affect the destruction of beta-cells by preexisting effectors other than macrophages. We conclude that macrophages are essential for the development of beta-cell-specific cytotoxic effectors in the initial phase of insulitis in NOD mice.

Animals↗

PubMed1996

Immune response to heat-shock protein correlates with induction of insulitis in I-E alpha d transgenic NOD mice.

To evaluate the correlation between heat-shock protein (HSP) and insulitis, we compared lymphocyte proliferative response to Mycobacterium leprae HSP65 of NOD mice with that of I-E alpha d transgenic NOD (I-E+NOD) mice, which show no insulitis. We found that splenocytes from 15-week-old NOD mice showed a more marked proliferative response to HSP than did those from age-matched I-E+NOD mice (P < 0.05). We then transferred splenocytes from 12-week-old NOD mice into I-E+NOD mice to induce insulitis in the recipients and examined antibody levels against HSP. By 6 weeks posttransfer, insulitis was successfully transferred to four out of five recipients of NOD splenocytes and antibody levels against HSP were significantly higher in the NOD splenocyte-transferred group than in controls, which showed no insulitis (P < 0.01). These results suggest that immune response to HSP correlates with insulitis in NOD mice. Our results support the assertion that HSP is a useful antigen for investigating the etiology of IDDM.

Animals↗

PubMedDate not supplied

Effect of scrotal insulation on clusterin-positive cells in ram semen and their relationship to semen quality.

Scrotal contents of 2 rams were insulated for 96 hours and the fraction (as a percentage) of clusterin-positive cells (CPCs) and its relationship to semen quality was investigated. Semen collection was started 18 days before insulation and was terminated on day 78 and day 63 after insulation in animals 1 and 2, respectively. Sperm clusterin was localized by immunostaining with anti-bovine clusterin antibody (anti-bCAb) and fluorescein isothiocyanate-conjugated immunoglobulin G. Scrotal insulation led to deterioration of semen quality and increased the percentage of CPCs in both rams. Two types of sperm reactivity were observed: an extensive, intensive staining pattern (ESP); and a localized, less-intensive staining pattern (LSP). The percentage of ESP-CPCs began to increase from day 6 and reached 88.8% and 100% on day 15 after insulation in animals 1 and 2, respectively. The increase in CPCs coincided with the presence of a high percentage of teratoid forms (88.3%) in semen from animal 1, and detached heads (81.4%) in semen from animal 2. After normal semen production was restored on day 60 in animal 1, the percentages of ESP-CPCs and LSP-CPCs returned to preinsulation rates, whereas only the ESP-CPCs returned to normal in animal 2. A negative relationship was observed between ESP-CPCs and total sperm/ejaculate (r = -.62), motility (r = -.78), viability (r = -.68), and filtration rate (r = -.71) in semen from animal 1. Conversely, a positive relationship was seen between ESP-CPCs and total abnormal spermatozoa (r = .82). Similar results were obtained in semen from animal 2. CPCs were nearly completely absent in glass wool-Sephadex (GWS)-filtered semen, suggesting a role for clusterin in the process of trapping abnormal spermatozoa in the GWS filters. We conclude that aberrant spermatogenesis induced by scrotal insulation increases the percentage of CPCs in ram semen. We suggest that the percentage of CPCs in ram semen could be a useful marker in poor-quality ejaculates.

Animals↗

PubMed2003

[Analysis of the sound-insulation effects of control rooms in workshops with noise].

OBJECTIVE: To study the main factors affecting sound-insulation effects of control rooms in workshops with noise, so as to improve the protection. METHODS: The sound-insulation effects of 467 control rooms were determined, and different building materials, structures of door and window, airtight states etc. were analyzed. RESULTS: The affecting factors contributed to the sound-insulation effects (Eta(2)) were in the order: airtight states (0.168), building materials (0.080), structures of window and door (0.030, 0.029), sound pressure levels and frequency spectrum's characteristics (0.008, 0.006). Under airtight state, the sound-insulation effects of different building materials of the rooms were as follows: double bricks [(19.6 +/- 3.5) dB(A)]; single brick [(15.4 +/- 3.4) dB(A)]; plank [(13.1 +/- 1.6) dB(A)] or aluminum alloy plate with glass [(13.4 +/- 2.5) dB(A)] (P < 0.01). Of 4 group rooms, with the same structure of doors but double or single bricks of windows. 3 groups with dormant window had higher sound-insulation effects [(15.9 +/- 2.8), (18.7 +/- 3.6), (19.3 +/- 2.5) dB(A)] than those with casement window [(14.1 +/- 2.4), (14.9 +/- 2.3), (16.5 +/- 2.4) dB(A)] (P < 0.01 or P < 0.05); 2 groups with dehydrated window [(18.7 +/- 3.3), (22.6 +/- 3.8) dB(A)] higher than those with dormant window [(15.9 +/- 2.8), (19.9 +/- 3.0) dB(A)] (P < 0.05). Of 6 group rooms, with the same structure of windows but double or single bricks of doors, only in 1 group with double-layer door had higher sound-insulation effect [(18.7 +/- 3.6) dB(A)] than that with single-layer door [(15.9 +/- 2.8) dB(A)] (P < 0.01). CONCLUSION: The control room should be designed rationally, kept airtight, according to the sound pressure levels and the condition of the workshop.

Environment Design↗

PubMed1989

The actual insulation of multilayer clothing.

The effect of geometric factors on insulation was calculated mathematically for standing humans. It was found that internal radiative heat transfer in an ensemble was significant for insulation, that intrinsic clothing insulation is a useful concept only for indoor climates, and that shape plays a minor role. The literature agrees closely on insulation and clothing surface area figures, and the latter are compatible with model predictions. Finally, it was shown that wind, body motion, the effects of posture, and the fit of garments are predictable. Sitting provides more insulation than standing for light clothing, but the reverse is true for heavy clothing. Insulation is decreased by about 20% by cycling and by about 40% by walking, and a reasonable estimate can be made of the effect of wind and wind and motion together. The effect of air motion on vapor permeability is stronger than the effect on heat transfer.

Air Movements↗

PubMed1986

Thermal insulation of materials with possible aerospace application.

Thermal insulation values for several materials that may have aerospace applications have been determined by a single method. Heat transfer across a specimen on a constant temperature heat source was measured by heat flow disc, and temperature on each side of the specimen was measured by thermistor. The data demonstrate that, with various thermal insulating materials, the primary factor in thermal insulation is the entrapped air. Where convective air currents were sufficiently reduced, insulative values for different materials varied only slightly. Reflective and nonreflective materials sandwiched into the insulators made little difference in these experiments, but if employed differently, might increase insulative values significantly.

Aerospace Medicine↗

PubMed1976

"Insulin" induced insulitis.

Insulitis, an inflammatory process restricted to the pancreatic islets, can experimentally be induced by active immunization with insulin or passive transfer of anti insulin serum. --Mice and rats injected with anti insulin serum from guinea pigs develop a polymorphcellular islet infiltration composed of many eosinophiles and neutrophiles. This inflammatory reaction is caused by the occurrence of immune complexes within the islet area produced by the injected insulin antibodies and the endogenous insulin. Thus polymorphcellular immune complex insulitis represents a type III immune response, respectively a local Arthus phenomenen. --Cattle, sheep and rabbits immunized with crystalline insulin preparations and Freund's adjuvant were found to develop a lymphoidcellular insulitis. As far as specific localization, histologic features, ultrastructure and an occasional manifestation of a diabetes mellitus-like syndrome are concerned lymphoidcellular immune insulitis suggests an immune response of the cell mediated type with temporary autoimmune characteristics to endogenous insulin evoked by the immunization with exogenous crystalline insulin. Insulin derivatives are the most probable candidates for the assumed insulitis-inducing antigen. --Whether immune reactions may also play a role in the pathomechanisms leading to human insulitis is until now an unsolved question.

Acute Disease↗

PubMed1994

The sequential appearance of sperm abnormalities after scrotal insulation or dexamethasone treatment in bulls.

Scrotal insulation and dexamethasone treatment were used as a model to compare the effect of testicular heating and stress on spermatogenesis. Insulation was applied to the scrotum of eight bulls (insulated) for a period of four days, eight bulls were treated daily for seven days with 20 mg dexamethasone injected intramuscularly, and four bulls were untreated controls. Semen from four bulls in each group was collected and evaluated over a six-week period after treatment. Blood samples for testosterone analysis were taken hourly for eight hours at the beginning and the end of the six-week period from the control bulls and before and after treatment from the four insulated and four dexamethasone-treated bulls that were not used for semen collection. At the end of the last blood sampling period, the four bulls in each group were castrated for the collection of testicular tissue for the determination of testosterone concentrations. Basal, peak episodic, and mean serum testosterone concentrations among control bulls, pre and postinsulated bulls, and pretreatment samples of dexamethasone-treated bulls were not different (p > 0.05); however, bulls that had received dexamethasone treatments had significantly lower basal, peak episodic, and mean testosterone concentrations (p < 0.05). Tissue concentrations of testosterone in control, insulated, and dexamethasone-treated bulls were not significantly different but tended to be lower in dexamethasone-treated bulls (p > 0.13). The spermiograms of the control bulls varied insignificantly over the six-week sampling period; however, there was a marked increase in sperm defects in insulated and dexamethasone-treated bulls. The types of sperm defects and the temporal relationships of rises and declines of sperm defects were quite similar for both treatments. All bulls recovered to approximately pretreatment levels of sperm defects by six weeks after the initiation of treatment. Results indicate that two of the most common types of insults to spermatogenesis in bulls, heat and stress, result in similar spermiograms.

Animals↗

PubMed2006

CTCF-dependent chromatin insulator is linked to epigenetic remodeling.

Chromatin insulators are boundary elements between distinctly regulated, neighboring chromosomal domains, and they function by blocking the effects of nearby enhancers in a position-dependent manner. Here, we show that the SNF2-like chromodomain helicase protein CHD8 interacts with the insulator binding protein CTCF. Chromatin immunoprecipitation analysis revealed that CHD8 was present at known CTCF target sites, such as the differentially methylated region (DMR) of H19, the locus control region of beta-globin, and the promoter region of BRCA1 and c-myc genes. RNA interference-mediated knockdown of CHD8 significantly abolished the H19 DMR insulator activity that depends highly on CTCF, leading to reactivation of imprinted IGF2 from chromosome of maternal origin. Further, the lack of CHD8 affected CpG methylation and histone acetylation around the CTCF binding sites, adjacent to heterochromatin, of BRCA1 and c-myc genes. These findings provide insight into the role of CTCF-CHD8 complex in insulation and epigenetic regulation at active insulator sites.

Animals↗

PubMed2003

Genomic insulators: connecting properties to mechanism.

Insulators are regulatory elements that establish independent domains of transcriptional activity within eukaryotic genomes. Insulators possess two properties: an anti-enhancer activity that blocks enhancer-promoter communication, and an anti-silencer activity that prevents the spread of repressive chromatin. Some insulators are composite elements with separable activities, while others employ a single mechanism to confer both properties. Recent studies focus on elucidating the molecular mechanisms of insulator function. Emerging themes support connections between insulators, transcriptional activators and topological chromosomal domains. Understanding these processes will provide insights into prevention of inappropriate regulatory interactions, knowledge that can be applied to gene therapies.

Animals↗

PubMed2004

Sea urchin insulator protects lentiviral vector from silencing by maintaining active chromatin structure.

Suppressed expression of transgenes in vivo is the major obstacle in the gene therapy. For the long-term expression, we utilized a chromatin insulator from sea urchin arylsulfatase (Ars) gene locus (Ars insulator, ArsI), which has been shown to epigenetically regulate gene expression across species. ArsI was able to prevent silencing of the transgene in a myeloid cell line, HL-60, and a murine embryonic stem cell line, CCE, in an orientation-dependent manner, but not in Huh-7, K562 and MCF-7 cells, indicating that the effect of ArsI on gene silencing was cell type dependent. Although anti-silencing effect of ArsI was almost equivalent to that of chicken beta-globin insulator, incorporation of ArsI into lentiviral vector had little effect on the virus titer compared with chicken beta-globin insulator. Clonal analysis of transduced HL-60 cells revealed that ArsI protects the lentiviral vector from position effects regardless of its orientation. Furthermore, chromatin immunoprecipitation assays revealed that a high acetylation level was observed in the promoter of the insulated vector, whereas that of ArsI was independent of its anti-silencing capacity. In addition to it having little deteriorative effect on the virus titer, the identified anti-silencing effect of ArsI suggested its possibility for application in gene therapy.

Acetylation↗

PubMed2005

Insulators are fundamental components of the eukaryotic genomes.

The properties of cis-regulatory elements able to influence gene transcription over large distances have led to the hypothesis that elements called insulators should exist to limit the action of enhancers and silencers. During the last decades, insulators have been identified in many eukaryotes from yeast to human. Insulators possess two main properties: (i) they can block enhancer-promoter communication ('enhancer blocker activity'), and (ii) they can prevent the spread of repressive chromatin ('barrier activity'). This review focuses on recent studies designed to elucidate the molecular mechanisms of the insulator function, and gives an overview of the critical role of insulators in nuclear organization and functional identity of chromatin.

Alleles↗

PubMed2003

Identification of an insulator in AAVS1, a preferred region for integration of adeno-associated virus DNA.

In latent adeno-associated virus (AAV) infection, the viral genome is integrated preferentially into the human chromosome 19 q arm at a specific region designated AAVS1, which has an open chromatin conformation as indicated by the presence of a DNase I-hypersensitive site (DHS-S1). We examined whether an insulator, which defines the domain of gene expression by directionally blocking the action of enhancers and by preventing the spread of heterochomatin, is present near the DHS-S1 in the middle of a 2.6-kbp AAVS1-related DNA fragment used in this study. The fragment, cloned into an Epstein-Barr virus (EBV)-based eukaryotic episomal plasmid, was introduced into HEK293 cells. The DHS-S1 on the plasmid replicating in the nuclei was hypersensitive to DNase I digestion, and thus, the EBV plasmid system was used in an enhancer-blocking assay with the 2.6-kbp DNA and two shortened DNAs, of 1.6 kbp and 336 bp, containing DHS-S1. The three DNA fragments, when inserted in the proper direction between the cytomegalovirus immediate-early enhancer and minimal promoter, repressed the expression of a reporter gene. Thus, the enhancer-blocking activity was located within the 336-bp DNA containing the entire region (300 bp) of DHS-S1. To investigate the prevention of repression caused by heterochromatin, a transgene-expressing cassette flanked by the two 336-bp DNAs placed in the enhancer-blocking direction was introduced into HEK293 and HeLa cells. All the cell clones examined with the cassette integrated into cell DNA continued to express the transgene, which indicates that the pair of 336-bp DNA apparently prevented the spread of heterochromatin. The results show that an insulator lies between nucleotides 17 and 354 near the DHS-S1 in AAVS1. In a gel shift test, the 336-bp DNA did not bind an in vitro-prepared CCCTC-binding factor that binds to the chicken beta-globin insulator, suggesting that the AAVS1 insulator requires an as yet unidentified binding protein. The newly identified AAVS1 insulator is likely to contribute to the maintenance of an open chromatin conformation that affects the life cycle of AAV.

Animals↗