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Biomedical subjects

J S Thompson

Publications and source records attributed to J S Thompson.

At least 19 recordsLinked to original sources
PubMed2003

Pulmonary vasodilation in the rat by insulin in vitro could indicate potential hazard for inhaled insulin.

AIMS/HYPOTHESIS: Hypoxic pulmonary vasoconstriction is an essential mechanism to prevent hypoxaemia in lung diseases. Insulin is known to be a systemic vasodilator but its effect on the pulmonary circulation is not known. Inhaled particulate insulin can generate locally high concentrations in the lung which could be physiologically important. METHODS: We therefore studied the effects of insulin in vitro on isolated rat pulmonary artery in a small vessel myograph. RESULTS: We have shown that pulmonary artery vasodilatation with insulin occurs in a dose-dependent manner. Pre-constriction with PGF2alpha can be abolished (105.7+/-2.9%, mean+/-SEM) and pre-constriction with hypoxia reduced (68.9+/-6.5%) by pharmacologically relevant concentrations of insulin. The characteristic phasic vasoconstriction by pulmonary vessel to hypoxia is substantially modified, resulting in sustained vasodilatation. CONCLUSIONS/INTERPRETATION: These effects could be clinically important for patients using inhaled insulins who have acute or occult chronic lung disease.

Animals↗
PubMed2003

Cellular origin of ionizing radiation-induced NF-kappaB activation in vivo and role of NF-kappaB in ionizing radiation-induced lymphocyte apoptosis.

PURPOSE: To investigate the cellular origin of ionizing radiation (IR)-induced NF-kappaB activation in vivo and the role of NF-kappaB in IR-induced lymphocyte apoptosis. MATERIALS AND METHODS: NF-kappaB activities were analysed by gel shift/supershift assay in isolated murine T- and B-cells, macrophages (MPhi) and tissues from normal and T- and B-cell-deficient Rag1 mice with or without exposure to IR. IR-induced lymphocyte apoptosis was determined by analysis of 3,3'-dihexyloxacarbocyanine iodide (DiOC(6)) uptake, annexin-V staining and the sub-G0/1 population, or by TUNEL assay. RESULTS: The results showed that IR activated NF-kappaB in lymphocytes, including both T- and B-cells, but failed to do so in MPhi. Furthermore, T- and B-cell-deficient Rag1 mice exposed to IR exhibited a significant reduction in NF-kappaB activation as compared with normal mice. Although NF-kappaB1 (p50) gene knockout or NF-kappaB decoy oligonucleotide treatment specifically inhibited IR-induced lymphocyte NF-kappaB activation, they had no significant effect on IR-induced lymphocyte apoptosis. CONCLUSIONS: This finding suggests that lymphocytes are the main cellular origin of IR-induced NF-kappaB activation in vivo. However, NF-kappaB activation has no significant effect on IR-induced lymphocyte apoptosis.

Animals↗
PubMed2002

Measurement of the electron affinity of cerium.

The electron affinity of cerium has been measured using laser photodetachment electron spectroscopy. The electron affinity of Ce(1G4) was determined to be 0.955 +/- 0.026 eV. The data also show that Ce- has at least two bound excited states with binding energies of 0.921 +/- 0.025 eV and 0.819 +/- 0.027 eV relative to the (1G4) ground state of the cerium atom. The present experimental measurements are compared to recent calculations of the energy levels of Ce-. Strong disagreement with the most recent theoretical atomic structure calculations highlights the complicated nature of this particular lanthanide.

Journal Article↗
PubMed2001

BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF.

B cell homeostasis has been shown to critically depend on BAFF, the B cell activation factor from the tumor necrosis factor (TNF) family. Although BAFF is already known to bind two receptors, BCMA and TACI, we have identified a third receptor for BAFF that we have termed BAFF-R. BAFF-R binding appears to be highly specific for BAFF, suggesting a unique role for this ligand-receptor interaction. Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which display a B cell phenotype qualitatively similar to that of the BAFF-deficient mice. Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature B cell survival.

Amino Acid Sequence↗
PubMed2001

Insulin pumps and glucose regulation.

With recent technologic advances there has been a resurgence of interest in implantable insulin infusion devices. A satisfactory closed loop system has been elusive. Open loop systems include the pump, delivery catheter, and patient pump communicator. Several such systems are currently undergoing clinical investigation. Implantable pumps can be placed with minimal morbidity. Insulin underdelivery is the most frequent long-term problem. Several recent studies suggest that implantable pumps can safely and effectively maintain good glucose control. The development of a satisfactory implantable closed loop system will be the next step in this technology.

Administration, Cutaneous↗
PubMed2001

Effects of NF-kappaB1 (p50) targeted gene disruption on ionizing radiation-induced NF-kappaB activation and TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression in vivo.

PURPOSE: To investigate the role of the NF-kappaB1 (p50) gene in ionizing radiation (IR)-induced NF-kappaB activation and TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression in vivo. MATERIALS AND METHODS: NF-kappaB activation was analysed by the gel shift/supershift assay and the levels of TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA were measured using RNase protection assay (RPA). Various tissues from BALB/c, B6,129P-Nfkb1 (NF-kappaB1 or p50 gene knockout, p50(-/-)) and B6,129PF2 (wild-type, p50(+/+)) mice were analysed before or after exposure to a lethal dose (8.5 Gy) of total-body gamma-irradiation. RESULTS: Exposure of BALB/c mice to total-body IR selectively activated NF-kappaB in the spleen, mesenteric lymph nodes (LN) and bone marrow (BM). Gel supershift assay using polyclonal antibodies against NF-kappaB p50, p65 or c-Rel protein revealed that the NF-kappaB p50 subunit is a critical component of the NF-kappaB complexes activated by IR in vivo. Discretely augmented TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression was found in the spleen, LN and BM after BALB/c mice received IR. However, mice lacking the p50 gene (p50(-/-)) showed a significant reduction in IR-induced activation of NF-kappaB and increases in TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression, as compared with that of wild-type mice (p50(+/+)). CONCLUSIONS: The NF-kappaB p50 subunit is a critical component of the NF-kappaB complexes activated by IR and it plays an important role in mediating IR-induced TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression in vivo.

Animals↗
PubMed2001

Effect of epidural anesthesia and analgesia on perioperative outcome: a randomized, controlled Veterans Affairs cooperative study.

OBJECTIVE: To test the hypothesis that epidural anesthesia and postoperative epidural analgesia decrease the incidence of death and major complications during and after four types of intraabdominal surgical procedures. SUMMARY BACKGROUND DATA: Even though many beneficial aspects of epidural anesthesia have been reported, clinical trials of epidural anesthesia for outcome of surgical patients have shown conflicting results. METHODS: The authors studied 1,021 patients who required anesthesia for one of the intraabdominal aortic, gastric, biliary, or colon operations. They were assigned randomly to receive either general anesthesia and postoperative analgesia with parenteral opioids (group 1) or epidural plus light general anesthesia and postoperative epidural morphine (group 2). The patients were monitored for death and major complications during and for 30 days after surgery, as well as for postoperative pain, time of ambulation, and length of hospital stay. RESULTS: Overall, there was no significant difference in the incidence of death and major complications between the two groups. For abdominal aortic surgical patients, unlike the other three types of surgical patients, the overall incidence of death and major complications was significantly lower in group 2 patients (22%) than in group 1 patients (37%), stemming from differences in the incidence of new myocardial infarction, stroke, and respiratory failure between the two groups. Overall, group 2 patients received significantly less analgesic medication but had better pain relief than group 1 patients. In group 2 aortic patients, endotracheal intubation time was 13 hours shorter and surgical intensive care stay was 3.5 hours shorter. CONCLUSIONS: The effect of anesthetic and postoperative analgesic techniques on perioperative outcome varies with the type of operation performed. Overall, epidural analgesia provides better postoperative pain relief. Epidural anesthesia and epidural analgesia improve the overall outcome and shorten the intubation time and intensive care stay in patients undergoing abdominal aortic operations.

Adult↗
PubMed2001

Mouth to pouch transit after restorative proctocolectomy: hydrogen breath analysis correlates with scintigraphy.

OBJECTIVES: Fast intestinal transit may be responsible for slow adaptation and unacceptable steady-state function after restorative proctocolectomy. Investigation of GI transit time may be valuable in such a setting. We hypothesized that postprandial hydrogen breath tests may yield transit data that correlate with technetium-labeled meal scintigrams. METHODS: This study compared intestinal transit after a lactulose and bean meal via the breath hydrogen and scintigraphy methods in 21 ileoanal pouch subjects. The meal consisted of baked beans (425 g), 30 ml (20 g) lactulose syrup, 1 mCi 99mtechnetium sulfur colloid in finely chopped liver and 170 ml tap water. The meal contained 120 Kcal (70% carbohydrate, 18% protein and 12% fat). RESULTS: Of 21 pouch subjects, 11 (53%) had breath tests and scintigraphy transit studies that differed by 5-21 min. Three of 21 (14%) scintigraphy mouth to pouch transit times were faster than breath test transits by 43-107 min. Seven of 21 (33%) subjects did not have breath test peaks >10 ppm. Mouth to pouch transit for breath hydrogen (104+/-16 min) and scintigraphy (98+/-7 min) tests had significant correlation (r = 0.96, p < 0.0001) among subjects with alveolar hydrogen peaks and accurate scintigrams (n = 11). Scintigrams were five times more expensive than breath tests. CONCLUSIONS: A peaking hydrogen breath test provides an alternative to scintigraphy for estimating intestinal transit after ileoanal pouch.

Adult↗
PubMed2001

D609 inhibits ionizing radiation-induced oxidative damage by acting as a potent antioxidant.

Tricyclodecan-9-yl-xanthogenate (D609) has been extensively studied in biological systems and exhibits a variety of biological functions, including antiviral, antitumor, and anti-inflammatory activities. Most of these activities have been largely attributed to the inhibitory effect of D609 on phosphatidylcholine-specific phospholipase C. However, as a xanthate derivative, D609 is a strong electrolyte and readily dissociates to xanthate anions and cations of alkali metals in solution. Xanthate anions and protonated xanthic acid contain a free thiol moiety and are highly reductive. This implies that D609 and other xanthate derivatives may function as potent antioxidants. Indeed, we found that D609 inhibited the Fenton reaction-induced oxidation of dihydrorhodamine 123 in a dose-dependent manner similar to that of pyrrolidinedithiocarbamate, a well known antioxidant. In addition, D609 inhibited the formation of the alpha-phenyl-tert-butylnitrone-free radical spin adducts and lipid peroxidation of synaptosomal membranes by the Fenton reagents. Furthermore, preincubation of lymphocytes with D609 resulted in a significant diminution of ionizing radiation (IR)-induced 1) production of reactive oxygen species; 2) decrease in intracellular reduced glutathione; 3) oxidative damage to proteins and lipids; and 4) activation of nuclear factor-kappaB. Moreover, when D609 (50 mg/kg i.v.) was administered to mice 10 min prior to total body IR (6.5 and 8.5 Gy), it protected the mice from IR-induced lethality. Thus, these results indicate that D609 is a potent antioxidant and has the ability to inhibit IR-induced cellular oxidative stress.

Animals↗
PubMed2000

Regulation of intestinal regeneration: new insights.

Intestinal regeneration is the process by which intestinal injury penetrating deep to the lamina propria heals. The regenerative process involves epithelial cell migration and proliferation, changes in cellular function, adaptation of subepithelial tissues, and contraction of the injured area. This requires interaction of multiple cell types. While many observations have been made about the process of regeneration, its regulation is not well understood. Previous studies, performed primarily in a serosal patch model, have identified many potential regulatory factors. These include location and size of the injury, other associated injury, e.g., resection, and a variety of agents that influence one or more of the primary processes involved. Epidermal growth factor (EGF), in particular, appears to play a role in many aspects of regeneration. Recent advances in the understanding of intestinal growth regulation have provided new insights into the regulation of intestinal regeneration. Developmental studies in genetically manipulated mice suggest a role for gene products not previously implicated in regeneration. The importance of apoptosis in growth regulation has recently been emphasized. Mesenchymal-epithelial interactions have gained greater appreciation. Finally, it has become clear that immune cells and cytokines are important factors in this process. Transforming growth factor-beta (TGFbeta) has been implicated as another important regulator of several of the processes involved in intestinal regulation. Improved understanding of the regulation of intestinal regeneration will lead to new therapeutic approaches to stimulate intestinal healing in the clinical setting.

Animals↗
PubMed2000

BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population.

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor-triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

Animals↗
PubMed2000

The influence of conventional and cross-reactive group HLA matching on cardiac transplant outcome: an analysis from the United Network of Organ Sharing Scientific Registry.

BACKGROUND: The short tolerable cold ischemia time and the importance of other risk factors have generally superseded the role of HLA matching in the allocation of donor hearts. Recent advances in the accuracy and time required to perform HLA typing and crossmatching, however, have led us to re-examine the United Network of Organ Sharing Transplant Registry for the effects of the HLA incompatibility on outcome in relation to other possible risk factors. METHODS: These include conventional HLA-A, -B, and cross-reactive group (CREG) mismatching (mm), HLA-DR mm, pretransplantation panel-reactive antibody (PRA), recipient and donor race and donor age, cold ischemia time, and the pretransplantation use of either a left ventricular assist device or an intra-aortic balloon pump. RESULTS: Three-year survival was clearly inferior in non-white (0.6921) as compared with white (0.7632) recipients, but this difference could not be accounted for by the degree of donor-recipient HLA mm that had occurred by chance. Nevertheless, the degree of mm that did occur seemed to have an impact on survival. The importance of HLA-DR mm was confirmed, and it ranked only behind the use of an assist device and recipient race in the multivariate analysis. HLA-A and B mm exerted an additional effect, but this was only true in white recipients. Of these, HLA-A achieved statistical significance as an independent risk factor. In general, CREG mm was not a significant variable. However, more than twice as many 0-1 or 0-2 CREG, 0 DR mm as compared with 0-1 or 0-2 A,B, 0 DR mm transplants enjoyed approximately equal and very good 1- and 3-year survival. Assuming no change is cold ischemia time, the potential number of 0 CREG, 0 DR mm, ABO-compatible transplants that could be achieved when an Organ Procurement Organization had 50-100 patients on their waiting list was calculated. The surprisingly high frequency of approximately 24-36% suggests that this favorable match could be considered along with other important factors in the local allocation process. When pretransplantation PRA was analyzed as a continuous variable from 0 to 100%, it was a highly significant risk factor, but this effect was more strikingly evident when the PRA was analyzed in 20% increments above zero. Recently, left ventricular assist device usage has become increasingly common, and it has been associated with strikingly increased pretransplantation PRA levels. When they occur together, the data indicates that these patients are at a very high risk for graft failure. CONCLUSIONS: We believe that newer typing and crossmatching techniques make it possible to add HLA criteria to the allocation protocol of donor cardiac organs and would lead to improved long-term survival.

Chi-Square Distribution↗
PubMed2000

Inflammatory disease and outcome of short bowel syndrome.

BACKGROUND: The outcome of the short bowel syndrome (SBS) is influenced by several factors including intestinal disease, remnant length and location, the other digestive organs, and intestinal adaptation. Because underlying inflammatory disease might influence several of these, the aim of this study was to evaluate the outcome of SBS in inflammatory conditions. METHODS: A total of 106 adult patients with SBS evaluated over a 20-year period were studied. Thirty (28%) patients had either Crohn's disease (n = 10) or radiation enteritis (n = 20). RESULTS: Multiple resections were more common in the inflammatory group (57% versus 12%, P <0.05.) These patients had longer intestinal remnants but the type of colonic remnant and the presence of an ileal remnant, the ileocecal junction and a stoma was similar in both groups. A similar proportion of patients in both groups required parenteral nutrition (PN) in the first year (73% versus 68%). Patients with inflammatory conditions were less likely to require PN after the first year (33% versus 63%; P<0.05). CONCLUSION: Patients with SBS resulting from inflammatory disease appear to have a better nutritional prognosis after the first year. While they are more likely to have had multiple resections and develop SBS with longer remnant length, inflammatory disease itself is an important prognostic factor. This may be related to resolution of inflammatory disease or a greater adaptive response.

Adult↗
PubMed2000

Using IRT to separate measurement bias from true group differences on homogeneous and heterogeneous scales: an illustration with the MMPI.

The authors present a didactic illustration of how item response theory (IRT) can be used to separate measurement bias from true group differences on homogeneous and heterogeneous scales. Several bias detection methods are illustrated with 12 unidimensional Minnesota Multiphasic Personality Inventory (MMPI) factor scales (Waller, 1999) and the 13 multidimensional MMPI validity and clinical scales. The article begins with a brief review of MMPI bias research and nontechnical reviews of the 2-parameter logistic model (2-PLM) and several IRT-based methods for bias detection. A goal of this article is to demonstrate that homogeneous and heterogeneous scales that are composed of biased items do not necessarily yield biased test scores. To that end, the authors perform differential item- and test-functioning analyses on the MMPI factor, validity, and clinical scales using data from 511 Blacks and 1,277 Whites from the California Youth Authority.

Adolescent↗