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L D Hudson

Publications and source records attributed to L D Hudson.

At least 19 recordsLinked to original sources
PubMed2001

Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome.

In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low tidal volume (VT) mechanical ventilation strategy (6 ml/kg) reduced mortality by 22% compared with traditional mechanical ventilation (12 ml/kg). In this study, we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality. The risk of death (before discharge home with unassisted breathing) was highest in patients with sepsis (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite these differences in mortality, there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor (p = 0.76, for interaction between ventilator group and risk factor). There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes: proportion of patients achieving unassisted breathing (p = 0.59), ventilator-free days (p = 0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for demographic and clinical covariates did not appreciably affect these results. After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions, there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups. In conclusion, we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS.

Adult↗
PubMed2001

Expression of the Krüppel-type zinc finger protein rKr2 in the developing nervous system.

Zinc finger transcription factors of the Krüppel-class figure prominently in cell fate specification and differentiation in the nervous system. One of the Krüppel-type genes that was originally cloned from an oligodendrocyte library by virtue of its homology with the prototypic Krüppel motif is the rat rKr2 gene (Pott et al., 1995). In primary cultures of rat glial cells, the rKr2 protein was only present in the oligodendrocyte lineage, predominantly in progenitors. Ninety percent of A2B5(+) oligodendrocyte progenitors displayed rKr2 immunoreactivity, while most MBP(+) oligodendrocytes lacked detectable rKr2. A similar pattern was found in vivo, in which the peak expression of rKr2 in the oligodendrocyte lineage of rats coincided with the wave of progenitor proliferation in early postnatal life. The subventricular zone, a source of neuronal and glial progenitors, displayed intense staining for rKr2 at late embryonic and postnatal stages. In the adult, cells within the remnants of this germinal zone continued to express rKr2 protein strongly. Some populations of mature neurons also displayed rKr2 immunostaining. Astrocytes and microglia were not labeled with the polyclonal anti-rKr2 antibody in vitro or in vivo. At all developmental stages, the rKr2 protein was localized to the nucleus. The stage-specific expression pattern and the subcellular localization of rKr2 recommend a role for this Krüppel-type gene in the progression of neural stem cells and in the early development of the oligodendrocyte lineage.

Animals↗
PubMed2001

Tracking oligodendrocytes during development and regeneration.

Over the past decade, advances in strategies to tag cells have opened new avenues for examining the development of myelin-forming glial cells and for monitoring transplanted cells in animal models of myelin insufficiency. The strategies for labelling glial cells have encompassed a range of genetic modifications as well as methods for directly attaching labels to cells. Genetically modified oligodendrocytes have been engineered to express enzymatic (e.g., beta-galactosidase, alkaline phosphatase), naturally fluorescent (e.g., green fluorescent protein), and antibiotic resistance (e.g., neomycin, zeomycin) reporters. Genes have been introduced in vivo and in vitro with viral or plasmid vectors to somatically label glial cells. To generate germ-line transmission of tagged oligodendrocytes, transgenic mice have been created both by direct injection into mouse fertilized eggs and by "knock-in" of reporters targetted to myelin gene loci in embryonic stem cells. Each experimental approach has advantages and limitations that need to be considered for individual applications. The availability of tagged glial cells has expanded our basic understanding of how oligodendrocytes are specified from stem cells and should continue to fill in the gaps in our understanding of how oligodendrocytes differentiate, myelinate, and maintain their myelin sheaths. Moreover, the ability to select oligodendrocytes by virtue of their acquired antibiotic resistance has provided an important new tool for isolating and purifying oligodendrocytes. Tagged glial cells have also been invaluable in evaluating cell transplant therapies in the nervous system. The tracking technologies that have driven these advances in glial cell biology are continuing to evolve and present new opportunities for examining oligodendrocytes in living systems. Microsc. Res. Tech. 52:766-777, 2001. Published 2001 Wiley-Liss, Inc.

Animals↗
PubMed2001

The transcriptional regulator Yin Yang 1 activates the myelin PLP gene.

Inauguration of the myelin program in developing oligodendrocytes requires the activation of those genes that encode the myelin proteins and the enzymes responsible for the synthesis and degradation of myelin lipids. An activator of the most abundantly expressed myelin protein, proteolipid protein (PLP), has been identified in a yeast one-hybrid system. The ubiquitously expressed zinc finger protein Yin Yang 1 (YY1) recognizes the myelin PLP promoter in vitro and in vivo. When overexpressed in an oligodendrocyte cell line, YY1 enhances transcription of the PLP promoter. A truncated version of YY1 that includes only the four zinc finger domains has little effect. The binding site for YY1 in the PLP promoter (site 3) fits the YY1 consensus site and DNA-protein complexes containing site 3 can be supershifted with an antibody directed against YY1 protein. Moreover, oligonucleotides with a mutated version of the PLP promoter site 3 are unable to bind to nuclear proteins or to compete for binding in a gel shift system. Finally, mutation of this site greatly reduces the activity of a 1-kb PLP promoter region in transfected glial cells. Our results suggest that PLP is a target gene for the transcriptional regulator YY1. This versatile transcription factor and nuclear matrix protein may boost transcription of the PLP gene to meet the demands of actively myelinating oligodendrocytes.

Animals↗
PubMed2001

Pemphigus.

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Humans↗
PubMed2001

Melanoma 2001.

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Humans↗
PubMed2001

Nitric oxide and nitrotyrosine in the lungs of patients with acute respiratory distress syndrome.

Nitric oxide (NO) end-products (nitrate and nitrite) are present in bronchoalveolar lavage (BAL) fluid of patients with inflammatory lung diseases. Reactive oxygen-nitrogen intermediates damage macromolecules by oxidation or nitration of critical residues in proteins. The goal of this study was to measure NO end-products (nitrate+ nitrite), in BAL fluid before and after the onset of acute respiratory distress syndrome (ARDS) and to determine if these products are associated with expression of inducible nitric oxide synthase enzyme (iNOS) in BAL cells and nitration of BAL proteins. We performed bronchoalveolar lavage (BAL) in patients at risk for ARDS (n = 19), or with ARDS (n = 41) on Days 1, 3, 7, 14, and 21 after onset, and measured total nitrite (after reducing nitrate to nitrite) and protein-associated nitrotyrosine concentration in each BAL fluid sample. Cytospin preparations of BAL cells were analyzed by immunocytochemistry for iNOS and nitrotyrosine. Nitrate+nitrite were detected in BAL fluid from patients at risk for ARDS, and for as long as 21 d after the onset of ARDS. Nitrotyrosine was detectable in all BAL fluid samples for as long as 14 d after the onset of ARDS (range, 38.8 to 278.5 pmol/mg of protein), but not in BAL of normal volunteers. Alveolar macrophages of patients with ARDS were positive for iNOS and nitrotyrosine, and remained positive for as long as 14 d after onset of ARDS. The BAL nitrate+nitrite did not predict the onset of ARDS, but the concentration was significantly higher on Days 3 and 7 of ARDS in patients who died. Thus, NO end products accumulate in the lungs before and after onset of ARDS; iNOS is expressed at high levels in AM during ARDS; and nitration of intracellular and extracellular proteins occurs in the lungs in ARDS. The data support the concept that NO-dependent pathways are important in the lungs of patients before and after the onset of ARDS.

Adult↗
PubMed2001

Anti-interleukin 8 autoantibody: interleukin 8 complexes in the acute respiratory distress syndrome. Relationship between the complexes and clinical disease activity.

Increased levels of interleukin 8 (IL-8) are found in bronchoalveolar lavage (BAL) fluids from patients with the acute respiratory distress syndrome (ARDS). However, IL-8 is not an efficient predictor of the course of ARDS. Our prior studies demonstrated that IL-8 present in lung fluids from patients with ARDS is associated with anti-IL-8 autoantibodies (anti-IL-8:IL-8 complexes). These data led us to hypothesize that the complexes might better predict the development of acute lung injury. Accordingly, we measured concentrations of free and complexed IL-8 in BAL fluids from 19 patients at risk and 45 with established ARDS on Days 1, 3, 7, 14, and 21 after the onset of ARDS. The concentrations of anti-IL-8:IL-8 complexes in patients with ARDS on Day 1 were significantly higher than in patients at risk (p < 0.05). There was a significant association between anti-IL-8:IL-8 complex concentrations and the onset of ARDS (p = 0.03). Similarly, anti-IL-8:IL-8 complex concentrations were significantly higher in patients on Day 1 of ARDS who later died (p < 0.05), and the association between high anti-IL-8: IL-8 complex concentrations and the probability of dying was significant (p = 0.03). The presence of anti-IL-8:IL-8 complexes in BAL fluids of patients with ARDS is an important prognostic indicator for the development and outcome of ARDS.

Adolescent↗
PubMed2000

Acute lung injury and acute respiratory distress syndrome. The clinical syndrome.

Acute lung injury (ALI) is a syndrome of severe acute respiratory failure defined by a constellation of clinical criteria. The exact incidence of ALI is not known, but it generally occurs in the setting of acute severe illness. The course of ALI after onset is quite variable, but outcome is associated with risk factor, age, and comorbidity. Survival from this syndrome has improved over time. Survivors often are impaired after hospital discharge but tend to improve over time; however, ALI does confer a significant additional burden on survivors with regard to pulmonary function and health-related quality of life.

Bronchoalveolar Lavage↗
PubMed2000

Modulation of neutrophil apoptosis by granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor during the course of acute respiratory distress syndrome.

OBJECTIVE: To determine whether bronchoalveolar lavage fluid (BALF) from patients either at risk for the acute respiratory distress syndrome (ARDS) or with sustained ARDS modulates neutrophil apoptosis; to measure the BALF concentrations of the apoptosis inhibitors granulocyte colony-stimulating factor (G-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) before and after the onset of ARDS; and to determine whether the BALF concentrations of G-CSF and/or GM-CSF are associated with clinical outcome. DESIGN: Prospective cohort study. SETTING: Tertiary university hospital. PATIENTS: Twenty patients at risk for ARDS and 45 patients with established ARDS. INTERVENTIONS: Patients at risk for ARDS underwent bronchoalveolar lavage within 24 hrs of being identified, then again 72 hrs later. Patients with ARDS underwent bronchoalveolar lavage within 24 hrs of meeting ARDS criteria, then again on days 3, 7, and 14 of the disease. MEASUREMENTS AND MAIN RESULTS: Normal peripheral blood neutrophil were incubated overnight in BALF from normal volunteers, from patients at risk for ARDS, or from patients with ARDS. neutrophil apoptosis was determined by flow cytometric analysis of annexin V binding. G-CSF and GM-CSF were measured in BALF by immunoassays. Compared with normal BALF, BALF from patients on days 1 and 3 of ARDS inhibited neutrophil apoptosis, but BALF from patients at later stages of ARDS, or from patients at risk for ARDS, did not. The BALF concentrations of both G-CSF and GM-CSF were elevated early in ARDS and decreased toward later stages. Patients who lived had significantly higher concentrations of GM-CSF in the BALF than those who died. CONCLUSIONS: We conclude that the antiapoptotic effect of ARDS BALF on normal neutrophil is highest during early ARDS, and decreases during late ARDS. G-CSF and GM-CSF are present in BALF from patients with ARDS, and their concentrations parallel the antiapoptotic effect of ARDS BALF. These data support the concept that the life-span of neutrophil in the air spaces is modulated during acute inflammation. GM-CSF in the air spaces is associated with improved survival in patients with ARDS.

Adolescent↗
PubMed2000

Diabetic patients have a decreased incidence of acute respiratory distress syndrome.

OBJECTIVE: Our ability to predict which critically ill patients will develop acute respiratory distress syndrome (ARDS) is imprecise. Based on the effects of diabetes mellitus on the inflammatory cascade, we hypothesized that a history of diabetes might alter the incidence of ARDS. DESIGN: A prospective multicenter study. SETTING: Intensive care units at four university medical centers. PATIENTS: One hundred thirteen consecutive patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were prospectively followed during their intensive care course for the development of ARDS. A history of diabetes was identified in 28% (32/113) of the patients. In this study, nondiabetics were more likely to develop septic shock from a pulmonary source (48%, 39/81) compared with diabetics (25%, 8/32) (p = .02). Forty-one percent (46/113) of the patients with septic shock developed ARDS. Forty-seven percent of the nondiabetic patients developed ARDS compared with only 25% of those with diabetes (p = .03, relative risk = 0.53, 95% confidence interval = 0.28-0.98). In a multivariate logistic regression analysis, when we adjusted for several variables including source of infection, the effect of diabetes on the incidence of ARDS remained significant (p = .03, odds ratio = 0.33, 95% confidence interval = 0.12-0.90). CONCLUSIONS: In patients with septic shock, a history of diabetes is associated with a lower risk of developing ARDS compared with nondiabetics.

APACHE↗
PubMed2000

Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta).

To determine the physiological roles of peroxisome proliferator-activated receptor beta (PPARbeta), null mice were constructed by targeted disruption of the ligand binding domain of the murine PPARbeta gene. Homozygous PPARbeta-null term fetuses were smaller than controls, and this phenotype persisted postnatally. Gonadal adipose stores were smaller, and constitutive mRNA levels of CD36 were higher, in PPARbeta-null mice than in controls. In the brain, myelination of the corpus callosum was altered in PPARbeta-null mice. PPARbeta was not required for induction of mRNAs involved in epidermal differentiation induced by O-tetradecanoylphorbol-13-acetate (TPA). The hyperplastic response observed in the epidermis after TPA application was significantly greater in the PPARbeta-null mice than in controls. Inflammation induced by TPA in the skin was lower in wild-type mice fed sulindac than in similarly treated PPARbeta-null mice. These results are the first to provide in vivo evidence of significant roles for PPARbeta in development, myelination of the corpus callosum, lipid metabolism, and epidermal cell proliferation.

Adipose Tissue↗
PubMed1999

Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control patients.

CONTEXT: Health-related quality of life (HRQL) is reduced in patients who survive acute respiratory distress (ARDS), but whether this decline in HRQL is caused by ARDS or other aspects of the patient's illness or injury is unknown. OBJECTIVE: To determine if there are differences in the HRQL of ARDS survivors and comparably ill or injured controls without ARDS. DESIGN: Prospective, matched, parallel cohort study. SETTING: A 411-bed municipal medical and regional level I trauma center. PATIENTS: Seventy-three pairs of ARDS survivors and severity-matched controls with the clinical risk factors for ARDS of sepsis and trauma admitted between January 1, 1994, and July 30, 1996. MAIN OUTCOME MEASURES: The HRQL of ARDS survivors and controls, assessed by generic and pulmonary disease-specific HRQL instruments (Medical Outcomes Study 36-Item Short Form Health Survey, Standard Form [SF-36] and St George's Respiratory Questionnaire [SGRQ], respectively). RESULTS: Clinically meaningful and statistically significant reductions in HRQL scores of ARDS survivors (n = 73) were seen in 7 of 8 SF-36 domains and 3 of 3 SGRQ domains compared with matched controls (P<.001 for all reductions). The largest decrements in the HRQL were seen in physical function and pulmonary symptoms and limitations. Analysis of trauma-matched pairs (n = 46) revealed significant reductions in 7 of 8 SF-36 domains (P< or =.02) and 3 of 3 SGRQ domains (P< or =.003). Analysis of sepsis-matched pairs (n = 27) revealed significant reductions in 6 of 8 SF-36 domains (P< or =.05) and 3 of 3 SGRQ domains (P< or =.002). CONCLUSIONS: Survivors of ARDS have a clinically significant reduction in HRQL that appears to be caused exclusively by ARDS and its sequelae. Reductions were primarily noted in physical functioning and pulmonary disease-specific domains.

APACHE↗
PubMed1999

Identification and characterization of early glial progenitors using a transgenic selection strategy.

To define the spatiotemporal development of and simultaneously select for oligodendrocytes (OLs) and Schwann cells (SCs), transgenic mice were generated that expressed a bacterial beta-galactosidase (beta-gal) and neomycin phosphotransferase fusion protein (betageo) under the control of murine 2'3'-cyclic nucleotide 3'-phosphodiesterase (muCNP) promoters I and II. Transgenic beta-gal activity was detected at embryonic day 12.5 in the ventral region of the rhombencephalon and spinal cord and in the neural crest. When cells from the rhombencephalon were cultured in the presence of G418, surviving cells differentiated into OLs, indicating that during development this brain region provides one source of OL progenitors. Postnatally, robust beta-gal activity was localized to OLs throughout the brain and was absent from astrocytes, neurons, and microglia or monocytes. In the sciatic nerve beta-gal activity was localized exclusively to SCs. Cultures from postnatal day 10 brain or sciatic nerve were grown in the presence of G418, and within 8-9 d exposure to antibiotic, 99% of all surviving cells were beta-gal-positive OLs or SCs. These studies demonstrate that the muCNP-betageo transgenic mice are useful for identifying OLs and SCs beginning at early stages of the glial cell lineage and throughout their development. This novel approach definitively establishes that the beta-gal-positive cells identified in vivo are glial progenitors, as defined by their ability to survive antibiotic selection and differentiate into OLs or SCs in vitro. Moreover, this experimental paradigm facilitates the rapid and efficient selection of pure populations of mouse OLs and SCs and further underscores the use of cell-specific promoters in the purification of distinct cell types.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS.

The goal of this study was to determine the changes that occur in surfactant-associated proteins in bronchoalveolar lavage fluid (BAL) and serum of patients at risk for ARDS and during the course of ARDS. We found that the concentrations of SP-A and SP-B were low in the BAL of patients at risk for ARDS before the onset of clinically defined lung injury, whereas the concentration of SP-D was normal. In patients with established ARDS, BAL SP-A and SP-B concentrations were low during the entire 14-d observation period, but the median SP-D concentrations remained in the normal range. Immunoreactive SP-A and SP-D were not increased in the serum of patients at risk for ARDS, but both increased after the onset of ARDS to a maximum on Day 3 and remained elevated for as long as 14 d. The BAL SP-A concentrations were significantly lower in at-risk patients who developed ARDS, and no patient with a BAL SP-A concentration greater than 1.2 microg/ml developed ARDS. On Days 1 and 3 of ARDS, the BAL SP-D concentration was significantly lower in patients who died, and the BAL SP-D concentration was significantly related to the PI(O(2))/FI(O(2)) ratio. Thus, surfactant protein abnormalities occur before and after the onset of ARDS, and the responses of SP-A, SP-B, and SP-D differ in important ways. The BAL SP-A and SP-D measurements can be used to classify patients as high or low risk for progression to ARDS and/or death after the onset of ARDS. Strategies to increase these surfactant proteins in the lungs of patients with ARDS could be useful to modify the onset or the course of ARDS.

APACHE↗
PubMed1999

The effect of acute respiratory distress syndrome on long-term survival.

Despite a great deal of information about the risk factors, prognostic variables, and hospital mortality in the acute respiratory distress syndrome (ARDS), very little is known about the long-term outcomes of patients with this syndrome. We conducted a prospective, matched, parallel cohort study with the goals of describing the survival of patients with ARDS after hospital discharge and comparing the long-term survival of patients with ARDS and that of a group of matched controls. The study involved 127 patients with ARDS associated with trauma or sepsis and 127 controls matched for risk factor (trauma or sepsis) and severity of illness who survived to hospital discharge. Time until death was used as the outcome measure. Survival was associated with age, risk factor for ARDS, and comorbidity. There was no difference in the long-term mortality rate for ARDS patients and that of matched controls (hazard ratio for ARDS: 1.00; 95% confidence interval: 0.47 to 2.09) after controlling for age, risk factor for ARDS, comorbidity, and severity of illness. We conclude that if sepsis or trauma patients survive to hospital discharge, ARDS does not increase their risk of subsequent death. Older patients, patients with sepsis, and patients with comorbidities, regardless of the presence of ARDS, have a higher risk of death after hospital discharge. For the purposes of clinical prognosis and cost-effectiveness analysis, the long-term survival of patients with ARDS can be modeled on the basis of age, underlying risk factor for ARDS, and comorbidity.

Adolescent↗