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Results for “Restrictive”

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PubMed1999

Respiratory protective devices: rates of medical clearance and causes for work restrictions.

BACKGROUND: There are no published data on the outcomes and benefits of medical evaluations for the use of respiratory protective devices. We, therefore, conducted a retrospective database and chart review to assess the rates of medical clearance and causes for work restrictions at a Department of Energy complex. METHODS: All workers with work restrictions or denied clearance over a one-year period were identified and their medical records abstracted. RESULTS: Of the 5,569 workers who received medical evaluation, only 71 (1.3%) received limitations on respirator use documented in their medical record. Of the 65 workers with sufficient medical records for additional analysis, 9 of the 5,569 workers (0.2%) were denied medical clearance, while 56 workers (1.1%) received work restrictions. Pregnancy was the most common cause for denying medical clearance for respirator use. Lung disease, cardiovascular disease, and claustrophobia were the most common causes for work restrictions. Physical examination and spirometry added little to the detection of relevant medical conditions. CONCLUSIONS: We conclude that few workers fail medical clearance for respirator use or receive work restrictions. Data on adverse events from respirator use are needed to help design appropriate medical evaluations and uniform criteria for work restrictions or denial of medical clearance.

Adult↗

PubMed1986

Capillary permeability in the pancreas and colon: restriction of exogenous and endogenous molecules by fenestrated endothelia.

The permeability properties of fenestrated capillaries in the colon and exocrine and endocrine pancreas to exogenous and endogenous molecules were examined. The exogenous tracers horseradish peroxidase (Einstein-Stokes radius [ESR], 3.0 nm), hemoglobin (ESR, 3.2 nm), and ferritin (ESR, 6.1 nm) were injected intravenously and allowed to circulate for 5-90 min. Tissues were removed and processed for cytochemical or standard electron microscopic examination. The endogenous plasma proteins albumin (ESR, 3.5 nm) and IgG (ESR, 5.5 nm) were localized by immunocytochemistry using the protein A-gold technique. All vessels examined were permeable to HRP in less than 5 min. In contrast, these vessels were restrictive to the slightly larger hemoglobin molecule (60-min circulation) and to ferritin (90-min circulation). Capillaries in the exocrine and endocrine pancreas were restrictive to albumin and IgG. These results demonstrate the presence of fenestrated capillary beds, in addition to the choriocapillaris, that are restrictive to molecules with ESR greater than or equal to 3.2 nm. Capillaries in the mucosa of the colon were restrictive to hemoglobin and ferritin but did not restrict albumin or IgG. This indicates that these vessels are of the permeable type. However, the rate of transendothelial movement of molecules is slower than that of other permeable vessels, such as in the ileo-jejunum. This study has provided further evidence for the existence of fenestrated endothelia that are restrictive to exogenous and/or endogenous molecules.

Animals↗

PubMed1992

Responses among New Jersey's largest employers to legislation restricting smoking at the worksite.

In 1985, New Jersey enacted a state law requiring that employers with more than 50 employees implement policies to control smoking in places of employment. The 104 largest private employers in New Jersey were surveyed in 1988 to assess their worksite smoking policies. Of the 92 respondents, 97% had implemented restrictive workplace smoking policies. Only 12% of respondents had implemented such policies prior to the date required by the law, and 86% cited the law as the reason for restricting smoking in the workplace. Over two-thirds of respondents placed restrictions on smoking in open areas, while only one-third restricted smoking in private offices. Nonsmoking employees were reported by 80% of respondents to be supportive of restrictive smoking policies, but 23% reported dissatisfaction by their smoking employees. The New Jersey law appears to have been an important factor in the adoption of work place smoking restrictions by the state's largest employers.

Attitude to Health↗

PubMed2005

The effects of feed restriction during organogenesis on embryo-fetal development in the rat.

BACKGROUND: Given the role of nutrition and body weight gain in normal development, pharmaceuticals intended to reduce appetite and promote weight loss will generate safety data that may be challenging to interpret. To aid with this, the effects of feed restriction and subsequent body weight reductions on embryo-fetal development were investigated in the rat. METHODS: Groups of 20 timed pregnant female Sprague-Dawley rats were offered Certified Rodent Diet 5002 either ad libitum or in restricted amounts of 20, 15, 10, and 7.5 g/day from Gestation Day (GD) 6-17. Clinical signs, body weights, and food consumption were recorded. Cesarean sections were performed on GD 21 and fetuses were sexed, weighed, and examined for external, visceral, and skeletal development. RESULTS: Mean maternal body weights at the end of the feed restriction period, GD 18, were reduced 0.87 x, 0.80 x, 0.69 x, and 0.63 x control mean in the 20, 15, 10, and 7.5 g/day groups, respectively. Mean body weight gains for the restriction period inclusive, GD 6-18, were 0.49 x and 0.24 x control at 10 and 7.5 g/day, respectively, and a mean body weight loss occurred at 10 and 7.5 g/day (0.95 x and 0.85 x mean GD 6 body weight, respectively). Fetal body weights were reduced 0.95 x, 0.93 x, 0.90 x, and 0.76 x control at 20, 15, 10, and 7.5 g/day, respectively. This resulted in a reduction in gravid uterine weight at 10 and 7.5 g/day. There were no external, visceral, or skeletal malformations attributed to feed restriction. There was an increase in the skeletal variation of wavy ribs and a decrease in ossification at 7.5 g/day. CONCLUSIONS: These data demonstrate that feed restriction-induced reductions in maternal gestational body weight gain of approximately 50% compared to ab lib fed rats only caused a reduction in fetal body weight. Even up to a 15% maternal gestational body weight loss had no effect on embryo viability in rats, but retarded fetal growth significantly enough to induce minor changes in skeletal development. There were no external, visceral, or skeletal malformations associated with any of the levels of maternal body weight reduction or loss.

Animal Feed↗

PubMed2006

Randomized clinical trial of the effect of postoperative intravenous fluid restriction on recovery after elective colorectal surgery.

BACKGROUND: Use of intravenous fluids is an important part of perioperative management. The aim of this study was to compare outcome following administration of restricted or standard postoperative intravenous fluids and sodium in patients undergoing elective colorectal surgery. METHODS: Eighty patients were randomized to restricted fluids (less than 2 litres water and 77 mmol sodium for 24 h after surgery) or a standard postoperative fluid regimen (3 litres water and 154 mmol sodium per day for as long as necessary). The primary endpoint was hospital stay. RESULTS: The median (i.q.r.) total intravenous fluid intake in the restricted group was 4.50 (4.00-5.62) litres compared with 8.75 (8.00-9.80) litres in the standard group (P < 0.001). Intravenous sodium intake was also significantly less in the restricted group (229 (131-332) versus 560 (477-667) mmol; P < 0.001). There was no difference in median time to first flatus (2.9 versus 2.9 days; hazard ratio (HR) 0.85 (95 per cent confidence interval (c.i.) 0.54 to 1.32); P = 0.466) or first bowel motion (4.7 versus 4.9 days; HR 1.06 (95 per cent c.i. 0.68 to 1.65); P = 0.802) between the restricted and standard groups, or in median hospital stay (7.2 versus 7.2 days; HR 1.03 (95 per cent c.i. 0.66 to 1.61); P = 0.902). CONCLUSION: Restriction of postoperative intravenous fluid and sodium does not reduce hospital stay following elective colorectal surgery.

Aged↗

PubMed2004

Up-regulation of activated macrophages in response to degeneration in the taste system: effects of dietary sodium restriction.

Dietary sodium restriction combined with unilateral chorda tympani nerve section leads to a rapid and specific decrease in neurophysiological taste responses to sodium in the contralateral, intact chorda tympani (Hill and Phillips [1994] J. Neurosci. 14:2904-2910). Previous work demonstrated that dietary sodium restriction may induce these early functional deficits by inhibiting immune activity after denervation (Phillips and Hill [1996] Am. J. Physiol. 271:R857-R862). However, little is known about the leukocyte response to denervation of taste buds in fungiform papillae. In the current study, it was hypothesized that T cells and macrophages are increased in the tongue after unilateral denervation in control-fed but not sodium-restricted animals. Adult, specified pathogen-free rats received unilateral chorda tympani nerve section or sham section followed by dietary sodium restriction or maintenance on control diet. At day 1, 2, 5, 7, or 50 postsectioning, immunostaining was used to detect the percentage of staining for activated macrophages, the number of alpha beta T cells, and the number of delta gamma epithelial T cells in the tongue. The number of lingual T cells did not significantly differ between treatment groups following denervation. However, there was a dramatic bilateral increase in ED1(+) staining for activated macrophages in control-fed rats that peaked at day 2 postsectioning. In contrast, sodium-restricted rats did not show an increase in activated macrophages above baseline at any time postsectioning. Further analysis of extralingual macrophages indicated that the deficit in immune activity in sodium-restricted rats is localized to the tongue and is not widespread. A model for immune modulation of taste receptor cell function is proposed based on these novel findings.

Analysis of Variance↗

PubMed1984

Development of home orientation in offspring of protein-restricted cats.

The development of home orientation was evaluated in 2-14-day-old kittens nursing from mothers fed a protein-restricted or control diet during late gestation and lactation. Although restricted kittens remained in the home when placed in it, their ability to return to the home was delayed when they were removed from it. Restricted kittens also exhibited aberrant locomotor development and an increased frequency of loss of balance (upsets) en route to the home. During postnatal Week 1, vocalization frequency, an index of kitten disturbance when outside the home, was increased in restricted kittens tested in the home, and in adjacent and diagonal corners. Restricted kittens persisted in vocalizing more frequently than controls in home and adjacent corner tests during Week 2. Taken together, these data suggest that maternal protein restriction during late gestation and lactation disrupts the development of home orientation behavior by impairing locomotor function and increasing emotional responsiveness.

Animals↗

PubMed1982

Expression of Qat-4 and Qat-5 alloantigens on cytotoxic precursor and effector cells: different surface phenotypes of alloreactive and H-2 restricted cytotoxic T cells.

Monoclonal anti-Qat-4 and anti-Qat-5 antibodies, which define antigens expressed on peripheral T cell subsets, have been used to study the phenotypes of alloreactive and H-2-restricted cytotoxic effector cells and their precursors. Depletion of Qat-4+ or Qat-5% cells from the T cell pool prior to their sensitization in bulk cultures prevented the development of alloreactive and H-2-restricted cytotoxic activities in the selected populations. No reconstitution of cytolytic activities to normal levels was obtained when mixtures of Qat-4- and Qat-5- cells were sensitized in bulk cultures to H-2 or non-H-2 antigens. Sensitization of limiting numbers of Qat-4- or Qat-5- lymphocytes under optimal conditions for help (interleukin 2), with the appropriated antigens (H-2 or H-Y) did not result in the generation of cytotoxic T cells, indicating that the majority of all cytotoxic T lymphocyte (CTL) precursors are Qat-4+, Qat-5+. When CTL effector populations were treated with the antisera and complement (C) at their maximum CTL activity, it was found that H-2-restricted CTL were totally eliminated by anti-Qat-4 and considerably reduced by anti-Qat-5 antisera and C. In contrast, alloreactive CTL effector cells were insensitive to anti-Qat-4 and to anti-Qat-5 plus C. Although alloreactive CTL effector populations regained some Qat-4 antigens during further in vitro culture, it was shown that H-2-restricted CTL were at all times more sensitive to anti-Qat-4 than were alloreactive CTL. The findings suggest that during maturation of alloreactive and H-2-restricted CTL from their precursors, both alloantigens undergo differential quantitative variations in their expression that lead to different Qat-4,5 phenotypes of alloreactive and H-2-restricted CTL.

Animals↗

PubMed1987

T cell activation by processed antigen is equally blocked by I-E and I-A-restricted immunodominant peptides.

The T cell response to a soluble protein requires the processing of the native antigen by an antigen-presenting cell (APC) to a peptide containing an antigenic determinant, which is transported to and bound on the antigen-presenting cell surface, where it is subsequently recognized by the specific T cell in the context of the appropriate Ia molecule. Investigating the response of a pigeon cytochrome c-specific, I-Ek-restricted T cell hybrid, which recognizes a determinant present within a 10-amino acid C-terminal fragment of the protein, it was previously demonstrated that peptides homologous to the peptide from pigeon cytochrome c, but which were not stimulatory, blocked the T cell response to pigeon cytochrome c as processed and presented by APC. In this report the ability of a series of fourteen, 20-amino acid overlapping peptides, representing the entire length of staphylococcal nuclease (Nase), were assessed for their ability to block the response of a pigeon cytochrome c-specific T cell hybrid to antigen-pulsed presenting cells. Only three Nase peptides blocked the I-Ek-restricted pigeon cytochrome c-specific T cell response. Two of these, Nase 61-80 and Nase 91-110, function as T cell antigens in the I-Ad and I-Ab-restricted response to Nase. The third blocking peptide, Nase 101-120, has not been shown to be a T cell antigen. Two other peptides, Nase 51-70 and Nase 81-100, which are recognized by Nase-specific T cells in the context of I-Ek, have no effect on the I-Ek-restricted cytochrome c-specific T cell response. None of these peptides block the higher affinity, heteroclitic response of pigeon cytochrome c-specific T cells to tobacco hornworm moth cytochrome c. Moreover, the response of an I-Ak-restricted T cell to ovalbumin was blocked by the I-Ek-restricted cytochrome c peptides from three different species. Thus, peptides with no obvious primary amino acid sequence homology, and which are not capable of being recognized in the context of the same Ia, compete with one another for the sites on the APC necessary for presentation of processed antigen to T cells. These results suggest that there are structures on the APC surface in addition to Ia, which are necessary for effective antigen presentation following processing. One suitable candidate for such a cell surface material is the recently identified peptide-binding protein, PBP72/74 (Lakey et al., Proc. Natl. Acad. Sci. USA 1987. 84: 1659).

Animals↗

PubMed1988

Growth-dependent variation of major histocompatibility complex (MHC) restriction and expression of Ly-2 and CD3/alpha/beta T cell receptor in cloned cytotoxic T cells.

The specificity of major histocompatibility complex (MHC)-restricted antigen recognition by cytotoxic T cells (CTL) has been clearly correlated to the alpha/beta T cell receptor (TcR) complex on the T cell surface. Occasional changes in the specificity of in vitro cultivated CTL clones, therefore, have been suspected to result from alterations of the genes coding for the TcR alpha and/or beta chain. Here we demonstrate that pronounced variations in the stringency of MHC restriction, previously reported to occur during long-term culture of 2,4,6-trinitrophenyl (TNP)-specific CTL clones, may occur rapidly in a growth-dependent, reversible manner, i.e. without structural TcR variation. Several H-2b TNP-specific CTL clones were shown to possess strong cross-reactivity for H-2k TNP target cells when seeded at low cell numbers, but exhibit reduced or undetectable cross-reaction to H-2k TNP in high-density cultures. Another clone revealed "heteroclitic" properties with significantly stronger cytotoxic activity towards allogeneic (H-2k) than syngeneic (H-2b) TNP-modified target cells. In this case dilute cultures appeared as exclusively allo-MHC restricted, whereas dense cultures were allo/self cross-restricted. In all instances these phenomena were accompanied by cell density-dependent quantitative changes in the expression of Ly-2 and T cell antigen receptor. CTL from dilute cultures had at least 2-fold higher surface concentrations of Ly-2 and CD3 antigens than cells from dense cultures while other surface markers such as Thy-1 or LFA-1 were completely identical. No such effects were observed for CTL clones exhibiting cell density-independent specificity patterns. We conclude from these findings that (a) the stringency of MHC restriction specificity may be significantly affected by the amount of expressed TcR and/or Ly-2 molecules, (b) CTL possess mechanisms to regulate Ly-2 and TcR expression and, hence, their MHC-restricted antigen recognition, and (c) the ability to regulate Ly-2 and TcR expression may be altered during prolonged culture of a CTL clone.

Animals↗

PubMed1989

DR3-restricted T cells from different HLA-DR3-positive individuals recognize the same peptide (amino acids 2-12) of the mycobacterial 65-kDa heat-shock protein.

Studies in experimental animals have demonstrated that the T cell response to immunogenic proteins is limited to one or a few epitopes on such proteins and that the MHC haplotype of the responder is an important factor in determining which epitope is recognized (immune response gene effect). However, if and to what extent MHC genes control the immune response to pathogens in man is virtually unknown. We have studied the human T cell response to the mycobacterial 65-kDa heat-shock protein, a major immunogen of Mycobacterium leprae and M. tuberculosis, the causative agents of leprosy and tuberculosis, respectively, in relation to HLA-DR phenotype. In a large panel of short-term cultured polyclonal anti-mycobacterial T cell lines, from 45 different individuals representing all DR-restriction specificities, only DR1 and DR3-restricted T cell lines proliferated to the 65-kDa protein. The DR1-restricted T cell lines responded to three new epitopes on the mycobacterial 65-kDa protein, one of which is specific for the M. tuberculosis complex. Altogether nine T cell epitope-containing regions have now been mapped on the 65-kDa protein and the response to each of them was exclusively restricted via one HLA-DR allele. Most importantly, all six 65-kDa-responsive DR3-restricted T cell lines from different individuals recognized an epitope on the same peptide, representing amino acids 2-12 of the 65-kDa protein, that was previously mapped using DR3-restricted T cell clones. From these data we conclude that the human T cell response to both the whole mycobacterial 65-kDa heat-shock protein and to defined epitopes on this protein is controlled by HLA-DR genes. The mycobacterial 65-kDa protein has been implicated in the design of subunit vaccines against tuberculosis and leprosy as well as the induction of immunopathology. In both instances the Ir gene control of the T cell response to this protein may have to be taken into account.

Antigen-Presenting Cells↗

PubMed2005

The role of CD1d-restricted NK T lymphocytes in the immune response to oral infection with Salmonella typhimurium.

CD1d-restricted natural killer T (NKT) cells belong to the innate-like lymphocytes which respond rapidly to stress and infectious challenge. We have studied murine CD1d-restricted NKT cells in the early immune response to virulent Salmonella enterica serovar Typhimurium after oral infection. In the liver and spleen, neutrophil and macrophage numbers had increased several-fold by day 5 post-infection, while the frequency of B and T lymphocytes decreased. These cellular changes occurred independently of CD1d-restricted NKT cells, and further, CD1d-restricted T cells did not influence the bacterial load. However, in CD1d(+) mice NK1.1(+) T cells and invariant CD1d-restricted T cells were activated by the infection, as demonstrated by an increase in size, up-regulation of CD69 and production of IFN-gamma. The NK1.1 antigen was down-modulated on these cells during the course of infection, while TCR levels were unaffected. While dendritic cells (DC) up-regulated CD1d-levels upon 24 h of in vitro exposure to the bacteria, increased CD1d expression was not evident on DC in vivo during infection. Furthermore, in vitro re-stimulation of CD1d-restricted T cells isolated from infected mice demonstrated a significant skewing of the cytokine profile, with suppressed IL-4 and increased IFN-gamma production.

Animals↗

PubMed2002

Chronic food restriction is associated with subtle dendritic alterations in granule cells of the rat hippocampal formation.

The hippocampal formation undergoes significant morphological and functional changes after prolonged feeding with low-protein diets. In this study we tested whether prolonged food restriction causes deleterious alterations in this brain region as well. It was found that the total number of dentate granule cells and hippocampal CA3 and CA1 pyramidal neurons did not differ between controls and rats submitted to food restriction (40%) for 36 weeks. Likewise, no effects of this dietary regimen have been detected on the morphology of the dendritic trees of hippocampal pyramids, and on the total number of the mossy fiber-CA3 synapses. By contrast, the dendritic arborizations of granule cells were found to have a reduced number of segments in food-restricted rats. However, the spine density on the distal segments of their dendritic trees and the total number of axospinous synapses in the outer molecular layer of the dentate gyrus were increased in these animals. In addition, the total dendritic length of the granule cells and the overall surface area of the active zones of the synapses in the outer molecular layer were preserved, indicating that the capacity of dentate granule cells to process afferent stimuli is likely to be unaffected by this dietary treatment. Supporting this view are the results obtained in the water maze experiment which show that food-restricted rats exhibit unimpaired spatial abilities, which are known to be dependent on the entorhinal drive towards the hippocampal formation. These results show that, among hippocampal neurons, dentate granule cells are selectively vulnerable to food restriction. Nonetheless, the reorganization which takes place in their dendrites and synapses is capable of minimizing the functional impairments that were expected to occur following changes in the hippocampal neuronal circuitry induced by this type of dietary restriction.

Animals↗

PubMed1982

A ts T mutant of Schmidt Ruppin strain of Rous sarcoma virus restricted at 39.5 degrees C for the morphological transformation and the tumorigenicity of chicken embryo fibroblasts.

In order to investigate a possible correlation between in vitro transformation and tumorigenicity in ovo, a new temperature-sensitive class T mutant of Rous Sarcoma Virus was isolated with a lower (39 degrees 5C) restrictive temperature for morphological transformation. This lower restrictive temperature was compatible with the survival of chicken and duck eggs for the tumorigenicity studies. In chicken embryo fibroblasts (CEF) infected by this new mutant, PA 17, and cultured at 39 degrees 5C, increase of hexose uptake, plasminogen activator production and anchorage-independent growth were only partially restricted, requiring incubation at 41 degrees 5C for a complete shut-off. Tumorigenicity in chicken and duck eggs inoculated with CEF infected and transformed by PA 17 was restricted at 39 degrees 5C, correlating well with the restriction of morphological transformation at this temperature. The kinase activity of the transforming protein pp60src in lysates of PA 17 infected cells cultured at permissive or restrictive temperatures was labile in RIPA buffer, as in the case of some previously examined ts T mutants. In the non-ionic detergent NP40 buffer, the kinase activity of PA17 infected cell lysates was better conserved and showed a moderate temperature dependence. These results suggest that, in spite of the correlations between the transformed cell phenotype in vitro and cell tumorigenicity in ovo, it is difficult to establish a quantitative relationship.

Allantois↗

PubMed1996

Differential metabolic effects of energy restriction in dogs using diets varying in fat and fiber content.

The role of dietary fat and fiber in energy restriction for the management of obesity was examined. Twelve male castrated dogs were energy restricted for 7 weeks by feeding 60% of their calculated maintenance energy requirements (MER = 1500 kcal/m2/d) for ideal body weight. Six dogs were restricted on a high-fat (35.4 kcal% from fat), low-fiber (2.9% dry matter basis [DMB]) diet while the other six dogs were restricted on a low-fat (24.5 kcal% from fat), high-fiber (27% DMB) diet. Compared with the high-fat, low-fiber diet, energy restriction on the low-fat, high-fiber diet resulted in significantly greater decreases in body fat (1472 +/- 166 vs. 853 +/- 176 g; p < 0.05) and total serum cholesterol concentrations (108.7 +/- 11.3 vs. 51.5 +/- 13.9 mg/dL; p < 0.005). Reductions in body weight (2.86 +/- 0.3 vs. 2.14 +/- 0.3 kg; p < 0.09), and mean arterial blood pressure (17.4 +/- 6.1 vs. 6.7 +/- 2.9 mmHg; p < 0.12) were also greater on the low-fat diet; however, these diet effects did not reach statistical significance. These data suggest that the fat and fiber content of the diet during energy restriction are important factors in the management of obesity.

Adipose Tissue↗

PubMed1995

Tissue specificity and mechanism of vitamin D receptor up-regulation during dietary phosphorus restriction in the rat.

Dietary phosphorus restriction up-regulates intestinal vitamin D receptor (VDR), but the tissue specificity of the up-regulation and the mechanism of receptor accumulation remain unknown. Therefore, the effects of low phosphorus diet (LPD) on VDR content in intestine, kidney, and splenic monocytes/macrophages were examined. Male Sprague-Dawley rats weighing 50-100 g were fed a normal diet (NPD; 0.6% Ca, 0.65% P) as controls followed by an LPD (0.6% Ca, 0.1% P) for 1-10 days (D1-D10). LPD rapidly decreased serum P levels by D1 from 11.11 +/- 0.19 mg/dl (mean +/- SE) to 4.98 +/- 0.37 mg/dl (n = 9). LPD increased total serum Ca from 10.54 +/- 0.09 mg/dl to 11.63 +/- 0.15, 12.17 +/- 0.15, and 12.39 +/- 0.18 mg/dl by D1, D2, and D3, respectively, and then remained stable. Serum 1,25-(OH)2D3 rapidly increased from 123 +/- 5.4 pg/ml to 304 +/- 35 pg/ml by D1, reached a plateau through D5, and then gradually increased to 464.9 +/- 27.7 pg/ml by D10. Intestinal VDR quantitated by ligand binding assay increased 3.5-fold from 169.6 +/- 13.7 fmol/mg of cytosol protein in rats fed NPD (n = 12) to a peak of 588.3 +/- 141.88 fmol/mg of protein by D3 (n = 6; p < 0.001) and then decreased to a plateau level of 2.5-fold greater than NPD (p < 0.05) during D5 to D10. In contrast, LPD did not up-regulate kidney or splenic monocyte/macrophage VDR. Northern blot analysis showed that intestinal VDR mRNA increased 2-fold by D2 (n = 3) of LPD and then gradually decreased to control levels after D5. In contrast, kidney VDR mRNA levels did not change during the first 5 days of P restriction and then subsequently decreased to 50% of NPD controls. The results of these studies indicate that VDR up-regulation during dietary phosphorus restriction is tissue-specific and that the mechanism of the up-regulation is time-dependent. Acutely (D1-D5), phosphorus restriction up-regulates intestinal VDR through increased VDR gene expression, whereas chronic (D5-D10) phosphorus restriction appears to alter VDR metabolism through nongenomic mechanisms that are consistent with prolongation of the half-life of the receptor. The nature of the tissue-specific regulation of VDR during phosphorus restriction remains to be determined.

Animals↗

PubMed2004

Mechanisms of beta cell death during restricted and unrestricted enterovirus infection.

Coxsackie B virus (CVB-5) infections potentially trigger and accelerate pancreatic beta cell damage leading to type 1 diabetes. In vivo, all viruses face natural resistance mediated by various host factors which restrict the progression of infection. Thus, the aims of this study were to generate a tissue culture model of restricted coxsackie B virus infection in primary islet cells by preventing the production of viral progeny with a selective inhibitor of viral RNA replication and to investigate the mechanisms of virus-induced islet cell death during productive and restricted infective conditions. Cultured foetal porcine islet cells were infected effectively with the prototype strain of coxsackievirus B5 (CVB-5). Nuclear viability stainings and electron microscopy showed productive infection to result in dominantly necrotic cell death with additional slight induction of apoptosis during the 7 days of follow-up. The restricted conditions were created by addition of guanidine-hydrochloride (G-HCl) into culture medium. At 1 mM concentration, it significantly protected the infected cells from necrosis and thus maintained high viability. This was associated with increased significantly apoptosis. In perifusion analysis, the cellular ability to release insulin was reduced, although the metabolic integrity was preserved as shown by MTT-analysis and cellular ATP levels. These data show that restriction of CVB-5 replication with G-HCl protects islet cells against virus-induced necrosis. However, restriction of viral replication shifts the mechanism of cell death from necrosis toward apoptosis. A slowly progressing subclinical infection of islets could thus lead to increased beta-cell apoptosis.

Adenosine Triphosphate↗

PubMed2002

Stereological quantification of placental villus vascularization and its relation to umbilical artery Doppler flow in intrauterine growth restriction.

The aim of this study was to investigate the changes in the number of vessels within tertiary stem villi and intermediate/terminal villi which may be responsible for the abnormalities in placental vascular resistance and Doppler velocity index values in growth-restricted fetuses. The placentas of 20 cases with intrauterine growth restriction and 30 cases which were appropriate for gestational age were studied. The umbilical artery resistance index, pulsatility index and systolic to diastolic ratio were measured in each case. The vessels were quantified by a stereological method described previously and vascular surface density and the volume portion of the villi were calculated. The placentas of preterm and term cases with intrauterine growth restriction displayed significant reductions in the vascular surface density of stem and intermediate/terminal villi and volume portion of intermediate/terminal villi stroma when compared with gestation-matched normally grown cases (p<0.05). There was no significant correlation between Doppler index values of the umbilical artery and the stereological parameters of the intermediate/terminal and stem villi in the intrauterine growth restriction group (p>0.05). Some of the pregnancies with intrauterine growth restriction (six patients) with normal Doppler flow velocity waveforms had reduced vascularization in the placentas, and these pregnancies were found to have no perinatal complications. We conclude that,although the placental villi show reduced vascularization in pregnancies with intrauterine growth restriction, the Doppler indices may be normal and this normal flow pattern is related to reduced complication rate.

Adult↗