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Biomedical subjects

K Bailey

Publications and source records attributed to K Bailey.

At least 37 records · Page 2Linked to original sources

An evaluation of federal order reform.

The Federal Agricultural Improvement and Reform Act of 1996 required the Secretary of Agriculture to reform federal milk marketing orders. The Secretary carried out this task and issued a final rule on March 31, 1999, that was eventually approved by dairy farmers in a national referendum. However, a temporary restraining order (TRO) was issued on September 28, 1999, that halted the reform process. The TRO was effectively overturned and the reform process restarted when President Bill Clinton signed the Consolidated Appropriations Act of 2000 on November 29, 1999. The final rule as amended consolidates the number of orders, develops a multiple component pricing system that determines new formulas for class prices, and provides a new system for pricing fluid milk based on county-level price differentials. The impact of these changes is to provide more transparency in pricing and improved market signals to farmers. But the new system is also much more vulnerable to changes in dairy commodity prices. The objective of this report is to provide a comprehensive overview of federal order reform and to analyze the impact of recent changes in class price formulas.

Animals↗

Usability evaluation of the progress note construction set.

OVERVIEW: The Veterans Administration (VA) Computerized Patient Record System (CPRS) is a nationally deployed software product that integrates provider order entry, progress notes, vitals, consults, discharge summaries, problem lists, medications, labs, radiology, transcribed documents, study reports, and clinical reminders. Users rapidly adopted the graphical user interface for data retrieval, but demanded options to typing for data entry. We programmed "point and click" forms that integrate with CPRS individually, but were soon overwhelmed by requests. Subsequently, we developed the Progress Note Construction Set (PNCS); a tool suite that permits subject matter experts without programming skills to create reusable "point and click" forms. In this study, we evaluate the usability of these user-constructed forms. METHODS: An untrained, non-VA subject matter expert used the PNCS to create a graphical form for "skin tear" documentation. Ten VA nurses used the skin tear form to document findings for 7 standardized clinical scenarios. Following each scenario the subjects answered usability questions about the form. RESULTS: The subject matter expert created the skin tear form in 78 minutes. Users found the form to facilitate their data entry (p 0.0265), and to be at least as fast (p 0.0029) and as easy to use as expected (p 0.0166). Average note entry time was 3.4 minutes. CONCLUSION: The PNCS allowed a non-programmer to quickly create a usable, CPRS-integrated point and click form. Users found the subject matter expert s form fast and easy to use. The tool suite is a more scaleable form creation method because capacity is no longer limited by programmer availability.

Medical Records Systems, Computerized↗

Cardiology services after stress testing: are there sex differences? A population-based study.

To test the hypothesis that, in a population-based cohort of persons undergoing stress tests, female sex was negatively associated with the use of cardiology visits in persons with no documented coronary artery disease (CAD) but that this association did not exist when CAD was established. Sex differences in the use of invasive cardiac procedures have been clearly documented, but data on physician encounters, an integral part of care, are lacking. A population-based cohort consisting of all Olmsted County, Minnesota residents who underwent an initial stress test in 1987, 1988, and 1989 in Olmsted County was examined. Medical records were reviewed for baseline characteristics including CAD diagnosis status, test results, and cardiology visits in the year following the stress test. Regression models were constructed to determine whether sex is independently associated with the probability of a visit. In the year after stress testing, there was no difference between the sexes in the use of inpatient (OR for female sex 0.88, 95% CI 0.62-0.97, P = 0.365) and outpatient/consultative (OR for female sex 1.24, 95% CI 0.95-1.61, P = 0.6) cardiology visits. Women were, however, less likely to receive preventive cardiology visits (OR for female sex 0.77, 95% CI 0.62-0.97, P = 0.02). This was largely related to less use of preventive visits among older women with documented coronary artery disease (CAD). In the absence of documented CAD, when the stress test was positive, women were less likely to receive preventive visits. In this geographically defined population within one year after an initial stress test, there was no sex difference in the use of in-patient or out-patient visits but women were less likely to receive preventive cardiology visits in the year after stress testing. Further studies are needed to understand the reasons for and impact of these care patterns.

Adult↗

Influence of cigarette smoking on crocidolite-induced ferritin release by human alveolar macrophages.

Alveolar macrophages (AMs) mobilize iron from the surface of iron-containing minerals such as asbestos and synthesize ferritin for intracellular iron storage or secretion. Although the synthesis of iron-free ferritin (apoferritin) provides antioxidant protection, the secretion of iron-containing ferritin by AMs could increase the availability of catalytic iron in the lungs. Cigarette smoking may promote the secretion of ferritin by AMs after iron acquisition from mineral sources, because smokers' AMs are iron loaded. The first objective of this study was to determine whether ferritin secretion/release by AMs after in vitro exposure to crocidolite asbestos is enhanced by cigarette smoking. The second objective was to assess whether exogenous ferritin-bound iron could enhance the toxicity of crocidolite to lung cells in vitro. AMs recovered from nonsmokers (n = 8) or smokers (n = 8) were exposed to crocidolite or titanium dioxide (TiO2)(1 x 10(6) AMs, 50 to 200 microg/mL) for up to 18 hours. AMs exposed to crocidolite but not TiO2 showed increased cell content of iron and ferritin and increased cell supernatant ferritin concentrations. Increases in iron and ferritin content were similar for AMs recovered from smokers and those recovered from nonsmokers; however, increases in supernatant ferritin were >7-fold greater for smokers' AMs than for nonsmokers' AMs (P < .001). Exposure of A549 cells, a lung cancer-derived cell line, to crocidolite (50 to 200 microg/mL, 18 hours) caused dose-dependent cell death as indicated by lactate dehydrogenase release. The addition of ferritin (> or = 500 mg/mL) but not apoferritin to culture media enhanced crocidolite-induced LDH release (P < .01). These findings suggest that cigarette smoking and crocidolite exposure have synergistic effects that promote ferritin release by AMs, which could catalyze oxidative injury to other alveolar cells.

Adult↗

The disinfection by-products dichloro-, dibromo-, and bromochloroacetic acid impact intestinal microflora and metabolism in Fischer 344 rats upon exposure in drinking water.

Human consumption of chlorinated drinking water has been linked epidemiologically to bladder, kidney, and rectal cancers. The disinfection by-product (DBP) dichloroacetic acid is a hepatocarcinogen in Fischer 344 rats and B6C3F1 mice. The objective of this study is to determine the effect of the DBPs dichloro-, bromochloro-, and dibromoacetic acids (DCA, BCA, DBA) on intestinal microbial populations and their metabolism, with emphasis on enzymes involved in the bioactivation of procarcinogens and promutagens. One-month-old male Fischer 344 rats were provided water ad libitum containing 1 g/l DCA, BCA, or DBA for up to 5 weeks. At 1, 3, and 5 weeks of treatment, beta-glucuronidase (GLR), beta-galactosidase (GAL), beta-glucosidase (GLU), nitroreductase (NR), azoreductase (AR), and dechlorinase (DC) activities were determined in cecal and small and large intestinal homogenates. After 5 weeks of treatment, intestinal populations were enumerated on selective media. Cecal GAL (DCA, BCA, DBA) and GLR (DCA, DBA) activities were reduced after 1 and 3 weeks of treatment and GAL activity was elevated at 5 weeks (BCA). Large intestinal GAL (DCA, BCA) and GLU (DCA, BCA, DBA) activities were elevated after 5 weeks of treatment. Week 5 cecal AR (DCA, BCA, DBA), NR (DCA), and DC (DCA, DBA) activities were reduced. Even though some significant changes in intestinal populations were observed, use of selective media was not sensitive enough to explain fluctuations in enzyme activity. Haloacetic acids in the drinking water alter intestinal metabolism, which could influence bioactivation of promutagens and procarcinogens in the drinking water.

Acetates↗

Acceptability of health status questionnaire screening and vaccination among Kosovar refugees.

During 1999, following the war in Kosovo, thousands of Kosovar refugees were received by different countries. The public health reception protocols for these refugees varied widely between and within reception countries. We surveyed a group of Kosovar refugees received in Bolton to assess the acceptability of vaccination and health status questionnaire screening. We also examined the refugees' opinions about the confidentiality of their medical history and their willingness to take part in research. Fifteen out of 29 people responded. Most respondents were happy with the interventions.

Adult↗

Ultrasensitive isotope trace analyses with a magneto-optical trap

Laser manipulation of neutral atoms has been used to count individual krypton-85 and krypton-81 atoms present in a natural krypton gas sample with isotopic abundances in the range of 10(-11) and 10(-13), respectively. This method of isotope trace analysis is free of contamination from other isotopes and elements and can be applied to several different isotope tracers for a wide range of applications. The demonstrated detection efficiency is 1 x 10(-7). System improvements could increase the efficiency by many orders of magnitude.

Journal Article↗

Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice.

Recent reports indicate an association between second trimester human influenza viral infection and later development of schizophrenia. Postmortem human brain studies also provide evidence for reduction in Reelin mRNA (an important secretory protein responsible for normal lamination of the brain) in schizophrenic brains. We hypothesized that human influenza infection in day 9 pregnant mice would alter the expression of reelin in day 0 neonatal brains. Prenatally-infected murine brains from postnatal day 0 showed significant reductions in reelin-positive cell counts in layer I of neocortex and other cortical and hippocampal layers when compared to controls. Whereas layer I Cajal-Retzius cells produced significantly less Reelin in infected animals, the same cells showed normal production of calretinin and nNOS when compared to control brains. Moreover, prenatal viral infection caused decreases in neocortical and hippocampal thickness. These results implicate a potential role of prenatal viral infection in causation of neuronal migration abnormalities via reduction in Reelin production in neonatal brains.

Animals↗

Effects of TNF-alpha and IL-1beta on iron metabolism by A549 cells and influence on cytotoxicity.

Extracellular iron, which is predominantly bound by transferrin, is present in low concentrations within alveolar structures, and concentrations are increased in various pulmonary disorders. Iron accumulation by cells can promote oxidative injury. However, the synthesis of ferritin stimulated by metal exposure for intracellular iron storage is normally protective. The cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta may alter iron metabolism by alveolar cells. In this study, we assessed the effects of TNF-alpha and IL-1beta on iron metabolism with a cell line with properties of type 2 alveolar epithelial cells (A549) exposed to non-transferrin-bound (NTBI; FeSO(4)) or transferrin-bound (TBI) iron. In addition, we assessed the cytotoxicity of these exposures by measuring the cell accumulation of malondialdehyde (MDA), a product of lipid peroxidation, and cell death (MTT assay and lactate dehydrogenase release). A549 cells treated with NTBI or TBI in concentrations up to 40 microM accumulated iron and synthesized predominantly L-type ferritin without accumulation of MDA or cell death. Treatment of A549 cells with TNF-alpha (20 ng) or IL-1beta (20 ng) decreased cell transferrin-receptor expression and induced synthesis of H-type ferritin. TNF-alpha and IL-1beta decreased the uptake of TBI; however, the uptake of NTBI was increased. Both cytokines enhanced total ferritin synthesis (H plus L types) in response to iron treatments due to enhanced synthesis of H-type ferritin. Coexposure to TNF-alpha and NTBI, but not to TBI, induced MDA accumulation and greater cytotoxicity (MTT and lactate dehydrogenase release) than TNF-alpha alone. These findings indicate that TNF-alpha and IL-1beta modulate iron uptake by A549 cells, with differing effects on TBI and NTBI, as well as on H-ferritin synthesis. Enhanced iron uptake induced by TNF-alpha and NTBI was also associated with increased cytotoxicity to A549 cells.

Cytotoxicity, Immunologic↗

Iron uptake promotes hyperoxic injury to alveolar macrophages.

Iron uptake by cells may increase the intracellular pool of prooxidant iron prior to storage of iron within ferritin. Because hyperoxia is toxic to alveolar macrophages (AM) via mechanisms involving oxidant stress, we hypothesized that iron uptake by AM might promote hyperoxia-induced injury. To assess this hypothesis, we cultured AM recovered from healthy volunteers under conditions of normoxia or hyperoxia (60% or 95% oxygen) in media of varying iron content, including control media (3 microM iron) and media supplemented with iron (FeCl3; total iron 10, 20, or 40 microM). AM injury was assessed by measuring release of lactate dehydrogenase (LDH), phagocytic activity for yeast, and cytosolic concentrations of calcium ([Ca2+]i) as determined by ratio image analysis of AM loaded with the fluorescent calcium probe indo-1. There was dose-dependent accumulation of iron and ferritin synthesis in AM exposed to iron-supplemented media. Exposure of AM to hyperoxia (60% and 95% oxygen, 18 h) in control media increased LDH release and impaired phagocytic activity for yeast; however, similar hyperoxic exposures in iron-supplemented media significantly increased the cells' LDH release and decreased phagocytosis. Exposure to 95% oxygen increased the [Ca2+]i of AM over 18 h, but similar exposure in iron-supplemented media induced greater increases in [Ca2+]i. As compared with exposure to normoxia, exposure to hyperoxia (60% and 95% oxygen) also decreased iron uptake and, to a greater extent, ferritin synthesis by AM in iron-supplemented media. These data suggest that: (1) iron uptake promotes hyperoxic injury to AM; and (2) hyperoxia impairs the capacity of AM to sequester iron in ferritin.

Bronchoalveolar Lavage Fluid↗

Increased concentrations of iron and isoferritins in the lower respiratory tract of patients with stable cystic fibrosis.

Reactive oxygen species may contribute to airway injury in patients with cystic fibrosis (CF) and iron catalyzes oxidant injury by promoting generation of highly reactive hydroxyl radicals. Iron in the lower respiratory tract may be free, ferritin bound (from which iron can be reductively mobilized), or transferrin bound (which generally prevents iron mobilization). Ferritin is composed of subunits that are heavy (H) or light (L), and H-rich ferritins have additional biologic effects including inhibition of lymphocyte proliferation and cell growth. To assess concentrations of iron and iron-binding proteins in the lower respiratory tract of patients with CF, we measured iron (ferrozine), L-ferritin, H-ferritin, and transferrin (enzyme-linked immunosorbent assay [ELISA]) in bronchoalveolar lavage (BAL) fluid recovered from stable patients with CF (n = 8), healthy nonsmokers (NS; n = 8), or heavy cigarette smokers (HS; n = 8). Iron was detected in BAL fluid from patients with CF and HS, but not NS, with higher iron concentrations in patients with CF (42.0 +/- 11.6 microgram/dl) than in HS (9.9 +/- 2.6 microgram/dl, p < 0.05). Ferritin was present in all BAL fluids, with higher total ferritin (L + H) in patients with CF (647 +/- 84 ng/ml) than in HS (181 +/- 25 ng/ml, p < 0.005) or NS (9 +/- 3 ng/ml, p < 0.0005). Ferritin recovered from HS and NS lungs was < 2% H type, whereas ferritin in CF lungs was > 40% H-type ferritin. Transferrin concentrations in BAL fluid were not different in any group. Tumor necrosis factor (TNF)-alpha was present only in BAL samples from patients with CF. To assess whether TNF-alpha contributed to H-ferritin accumulation in CF lungs, we treated lung epithelial cells (A549) with iron alone (FeSO(4), 10-40 microM) or with iron and TNF-alpha (5-20 ng/ml). Iron-treated A549 cells synthesized almost entirely L-ferritin whereas exposure to TNF-alpha with iron caused a dose-dependent increase in accumulation of H-type ferritin. These findings suggest that oxidant injury could be promoted in lungs of patients with cystic fibrosis by iron mobilized from extracellular ferritin and, in addition, that TNF-alpha-promoted accumulation of H-type ferritin may impair local immune function and cell growth.

Adult↗

A longitudinal evaluation of a communication skills programme.

Communication is an essential component of palliative care, but patients and their families are often dissatisfied with their interactions with health professionals. Communication difficulties are also a recognized stress factor among health professionals. Education and training, however, are said to improve communication skills. A communication skills training programme for 110 nurses has demonstrated statistically significant improvements in the nurses' skills, but no long-term effect was evaluated. This paper presents the results of the long-term follow-up study. Of the 110 nurses contacted, 20% refused to participate, 45% agreed and 35% did not respond; 33 nurses returned usable data. The mean length of time since completing the original study was 2.5 years. Since completion of the original course there was no statistically significant deterioration or improvement in eight of the nine areas of assessment skills evaluated. In the area of psychological assessment there was a statistically significant improvement, and overall the nurses maintained their skills and improved in this area. The results suggest that over time the nurses became more confident in the emotional areas of care as a result of the training. The two key elements of the training were audio-tape recordings and feedback, which raised self-awareness, and experiential workshops covering ways of handling difficult situations. Whether a similar training effect could be achieved by a short 3-5 day course on communication skills needs addressing, because the integrated training skills course evaluated here is costly. Preliminary evidence suggests that the 3-5-day course may not be as effective, so the increased costs associated with the integrated training skills course may be wisely spent if it improves the quality of nurse-patient interaction as evidence here suggests.

Adult↗

Intrapulmonary cytokine accumulation following BAL and the role of endotoxin contamination.

STUDY OBJECTIVES: BAL induces alveolar inflammation, but its effects on intrapulmonary cytokines and the mechanisms causing inflammation are uncertain. The objectives of this study were: (1) to characterize cytokine response in the lungs to BAL, and (2) to determine whether endotoxin is introduced into the lungs during BAL, which could promote BAL-induced inflammation. DESIGN AND METHODS: We performed two BAL procedures in healthy volunteers separated by 4 (n=6), 24 (n=5), or 72 h (n=3). The initial BAL was performed in the right middle lobe (RML) and the second BAL was performed in the same location and the lingula. Concentrations of interleukin-8 (IL-8), interleukin-1 (IL-1beta), and transforming growth factor-beta were measured by enzyme-linked immunosorbent assay and tumor necrosis factor-alpha (TNF-alpha) bioactivity was determined. Endotoxin contents of saline (10 and 20 mL) infused through bronchoscopes as well as BAL fluids recovered from six subjects were assessed by limulus amebocyte assay. RESULTS: At 4 h after the initial lavage, but not at later times, BAL fluid recovered from the RML contained increased concentrations of IL-8 and IL-1beta, and increased TNF-alpha bioactivity. BAL fluid recovered from the lingula contained increased concentrations of TNF-alpha only at 4 h. All BAL samples tested contained detectable endotoxin as did all saline aliquots instilled through bronchoscopes. CONCLUSIONS: There is intrapulmonary accumulation of the cytokines TNF-alpha, IL-8, and IL-1beta in the lavaged lung within 4 h after BAL; this accumulation resolves by 24 h. Endotoxin contamination of the lungs during bronchoscopy may contribute to BAL-induced lung inflammation.

Adult↗

Differential expression of synaptosome-associated protein 25 kDa [SNAP-25] in hippocampi of neonatal mice following exposure to human influenza virus in utero.

We investigated the role of maternal exposure to human influenza virus [HI] in C57BL/6 mice on day 9 of pregnancy on the hippocampal expression of SNAP-25 in postnatal day 0 neonates, and compared them to sham-infected pups. The expression of SNAP-25 in infected neonates varied along the septotemporal axis of hippocampus and in various anatomic layers. Quantitative densitometric analysis of specific immunogold silver-enhanced SNAP-25 immunoreactivity [IR] showed increases of 40-347% over control in all septal-dorsal hippocampal layers except for the subplate layer. In mid septo-temporal hippocampus, SNAP-25 IR increased by 10-114% over control in all layers, except for the hippocampal plate, but the extent of this increase was smaller than in the dorsal-septal area. Finally,in temporal-ventral levels, SNAP-25 expression was reduced in all infected layers by 21-33% below control except for mild increases of 8.8 and 10% in subplate and hippocampal plate layers. Additionally, the infected SNAP-25 maximal density bin shifted to lower values dorsally and to higher values medially, with ventral maximal bins remaining unchanged when compared to controls. The differential expression of SNAP-25 in the hippocampi of infected neonates indicates a variable degree of vulnerability across the septo-temporal axis of hippocampus. It is surmised that while viral infection may induce excitotoxicity in the ventral hippocampus, it may cause reactive synapto-genesis in the medial and dorsal sectors of the developing brains of postnatal day 0 neonates.

Animals↗

Human influenza viral infection in utero increases nNOS expression in hippocampi of neonatal mice.

We investigated the role of maternal exposure to human influenza virus (HI) in C57BL/6 mice on day 9 of pregnancy on hippocampal expression of nNOS in day 0 neonates and compared that to sham-infected pups. Qualitative analysis using polyclonal antibody to nNOS showed overall increases in immunoreactivity (IR) in hippocampal and dentate layers of day 0 infected neonates when compared to sham-infected animals. These increases in nNOS immunoreactivity were pronounced in hippocampal plate, intermediate, molecular, subplate, and dentate areas. Quantitative analysis of specific immunogold silver-enhanced nNOS IR via densitometry showed nNOS IR increases of 26-71.6% in all layers, i.e., hippocampal plate (35.1%), dentate area (71.6%), molecular area (43.75%), subplate (45.7%), and intermediate zone (26%) in infected neonatal brains vs. controls. The changes in levels of nNOS expression in hippocampi of neonates born to mothers exposed to HI virus during the second trimester of pregnancy may reflect the potential for glutamatergic excitotoxicity via activation of NMDA receptors in the developing brains of these neonatal mice.

Animals↗

Treatment with either high or low frequency TENS reduces the secondary hyperalgesia observed after injection of kaolin and carrageenan into the knee joint.

For years, physical therapists have been utilizing a variety of modalities, including transcutaneous electrical nerve stimulation (TENS), in an attempt to manage pain associated with inflammation. However, the data on clinical effectiveness is conflicting and the neurophysiological mechanism of action is not known. The purpose of this study was to investigate the effects of high and low frequency TENS on the secondary hyperalgesia that occurs after joint inflammation. Secondary hyperalgesia is thought to reflect changes in central neurons and is thus a measure of activity of central neurons. This study utilized the kaolin and carrageenan model of knee joint inflammation and measured the effects of TENS treatment on paw withdrawal latency to radiant heat (secondary hyperalgesia), spontaneous pain behaviors and joint circumference. Either high (100 Hz) or low (4 Hz) frequency TENS was applied to the knee joint for 20 min after the development of hyperalgesia. Both high and low frequency TENS resulted in a reversal of the hyperalgesia immediately following treatment. The effects of high frequency TENS lasted through at least 24 h while those of low frequency TENS lasted through 12 h. There was no effect of TENS on spontaneous pain behaviors or joint swelling when compared to controls. Thus, TENS appears to be more effective in reducing referred pain (or secondary hyperalgesia) without affecting guarding or splinting of the affected limb. Thus, clinically, the choice to use TENS may depend on patient symptoms; specifically TENS should be effective in reducing referred or radiating pain.

Animals↗

The effect of three different doses of tranexamic acid on blood loss after cardiac surgery with mild systemic hypothermia (32 degrees C).

OBJECTIVE: Prophylactic administration of tranexamic acid (TA), an antifibrinolytic agent, decreases bleeding after cardiac surgery with systemic hypothermia (25 degrees C to 29 degrees C). Warmer systemic temperatures during cardiopulmonary bypass (CPB) may reduce bleeding and thus alter the requirement for TA. The effect of three different doses of TA on bleeding after cardiac surgery with mild systemic hypothermia (32 degrees C) is evaluated. DESIGN: Double-blind, prospective, randomized study. SETTING: University hospital. PARTICIPANTS: One hundred fifty adult patients undergoing aortocoronary bypass or valvular cardiac surgery. INTERVENTIONS: Patients received TA, 50 (n = 50), 100 (n = 50), or 150 (n = 50) mg/kg intravenously before CPB with mild systemic hypothermia. MEASUREMENTS AND MAIN RESULTS: Blood loss through chest drains over 6, 12, and 24 hours after surgery and total hemoglobin loss were measured. Autotransfused blood, transfused banked blood and blood products, and coagulation profiles were measured. Analysis of variance on log-transformed data for blood loss and confidence intervals (CIs) of 0.95 were calculated and transformed to milliliters of blood. No patient was re-explored for bleeding. Blood loss at 6 hours was statistically greater in the 50-mg/kg group compared with the other two groups (p = 0.03; p = 0.02). Total hemoglobin loss was statistically greater in the 50-mg/kg group compared with the 150-mg/kg group (p = 0.04). There was no statistical difference in blood tranfusion rate or coagulation profiles among the three groups. However, preoperative hemoglobin level was statistically lower in the 150-mg/kg group compared with the other two groups (p = 0.01). CONCLUSION: Of the three doses of TA studied, the most efficacious and cost-effective dose to reduce bleeding after cardiac surgery with mild hypothermic systemic perfusion is 100 mg/kg.

Adult↗

Potential role of epithelial cell-derived histone H1 proteins in innate antimicrobial defense in the human gastrointestinal tract.

In the human gastrointestinal tract, microorganisms are present in large numbers in the colon but are sparse in the proximal small intestine. In this study, we have shown that acid extracts of fresh human terminal ileal mucosal samples mediate antimicrobial activity. Following cation-exchange chromatography, one of the eluted fractions demonstrated antibacterial activity against bacteria normally resident in the human colonic lumen. This activity was further fractionated by reverse-phase high-performance liquid chromatography and identified as histone H1 and its fragments. We have also shown that in tissue sections, immunoreactive histone H1 is present in the cytoplasm of villus epithelial cells. In vitro culturing of detached (from the basement membrane) villus epithelial cells led to the release of antimicrobial histone H1 proteins, while the cells demonstrated ultrastructural features of programmed cell death. Our studies suggest that cytoplasmic histone H1 may provide protection against penetration by microorganisms into villus epithelial cells. Moreover, intestinal epithelial cells released into the lumen may mediate antimicrobial activity by releasing histone H1 proteins and their fragments.

Amino Acid Sequence↗