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1.
Genetics ; 163(3): 1123-34, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12663549

ABSTRACT

Single-nucleotide polymorphisms (SNPs) provide an abundant source of DNA polymorphisms in a number of eukaryotic species. Information on the frequency, nature, and distribution of SNPs in plant genomes is limited. Thus, our objectives were (1) to determine SNP frequency in coding and noncoding soybean (Glycine max L. Merr.) DNA sequence amplified from genomic DNA using PCR primers designed to complete genes, cDNAs, and random genomic sequence; (2) to characterize haplotype variation in these sequences; and (3) to provide initial estimates of linkage disequilibrium (LD) in soybean. Approximately 28.7 kbp of coding sequence, 37.9 kbp of noncoding perigenic DNA, and 9.7 kbp of random noncoding genomic DNA were sequenced in each of 25 diverse soybean genotypes. Over the >76 kbp, mean nucleotide diversity expressed as Watterson's theta was 0.00097. Nucleotide diversity was 0.00053 and 0.00111 in coding and in noncoding perigenic DNA, respectively, lower than estimates in the autogamous model species Arabidopsis thaliana. Haplotype analysis of SNP-containing fragments revealed a deficiency of haplotypes vs. the number that would be anticipated at linkage equilibrium. In 49 fragments with three or more SNPs, five haplotypes were present in one fragment while four or less were present in the remaining 48, thereby supporting the suggestion of relatively limited genetic variation in cultivated soybean. Squared allele-frequency correlations (r(2)) among haplotypes at 54 loci with two or more SNPs indicated low genome-wide LD. The low level of LD and the limited haplotype diversity suggested that the genome of any given soybean accession is a mosaic of three or four haplotypes. To facilitate SNP discovery and the development of a transcript map, subsets of four to six diverse genotypes, whose sequence analysis would permit the discovery of at least 75% of all SNPs present in the 25 genotypes as well as 90% of the common (frequency >0.10) SNPs, were identified.


Subject(s)
Glycine max/genetics , Polymorphism, Single Nucleotide , Transcription, Genetic , DNA Primers , DNA, Plant/genetics , Enzymes/genetics , Gene Amplification , Gene Expression Regulation, Plant , Genetic Markers , Genotype , Haplotypes , Plant Proteins/genetics , Polymerase Chain Reaction , Polymorphism, Single Nucleotide/genetics , Glycine max/classification , Glycine max/enzymology
2.
Clin Auton Res ; 11(1): 29-34, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11503947

ABSTRACT

The effects of autonomic dysfunction and regular activity on the cardiovascular system were investigated. The 48 participants included 12 subjects with tetraplegia, 12 subjects with paraplegia, 12 sedentary subjects, and 12 endurance-trained able-bodied controls. Central and peripheral autonomic data were obtained at rest to estimate efferent cardiac vagal output and sympathetic vasomotor control, and plasma norepinephrine concentration was determined as a marker of peripheral sympathetic activity. Cardiovascular parameters were obtained using a noninvasive cardiac output maneuver. The group with paraplegia did not differ from the sedentary group for efferent cardiac vagal output, but all other group comparisons were different (p <0.05). Sympathetic vasomotor control and stroke index were also similar between the paraplegia and sedentary groups, whereas both were increased in the endurance-trained group and were significantly reduced in the tetraplegia group. A strong relation between efferent cardiac vagal output and stroke index was established for the total group (r = 0.78, p <0.01), and analysis of covariance determined that the slope of this relation was similar among the groups. Sympathetic vasomotor control correlated significantly with plasma norepinephrine (r = 0.57, p <0.01), and a relation between sympathetic vasomotor control and stroke index was identified for the total group (r = 0.40, p <0.01). These results suggest that vagal control of resting central cardiac function is maintained despite autonomic dysfunction. The comparable findings in the paraplegia and sedentary groups suggest that regardless of peripheral autonomic dysfunction, the absence of regular physical activity has a similar effect on the resting vagal modulation and stroke index.


Subject(s)
Autonomic Nervous System Diseases/physiopathology , Cardiovascular System/innervation , Cardiovascular System/physiopathology , Physical Education and Training , Physical Endurance , Adult , Autonomic Nervous System Diseases/etiology , Efferent Pathways/physiopathology , Humans , Life Style , Male , Middle Aged , Paraplegia/complications , Quadriplegia/complications , Reference Values , Vagus Nerve/physiopathology , Vasomotor System/physiopathology
3.
Cell Mol Life Sci ; 58(1): 148-59, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11229814

ABSTRACT

Factor V is a plasma protein essential for blood coagulation. This protein is involved in activated protein C resistance, the most common inherited thrombotic disorder known. We utilized the polymerase chain reaction to clone the porcine factor V gene by generating overlapping clones amplified with primers chosen by comparison with known nucleotide sequences. The porcine factor V cDNA contig encodes a predicted 2258-amino acid protein, making it the largest in comparison to the bovine, human, and murine proteins. Porcine factor V has the highest level of homology with bovine factor V, but also has high levels of conservation of important residues with all the species. Radiation hybrid mapping assigned the porcine factor V gene to chromosome 4. Three-dimensional models of factor V were generated and used to analyze membrane-binding sites in terms of conserved, and therefore likely important residues.


Subject(s)
Cell Membrane/metabolism , Factor V/chemistry , Factor V/genetics , Radiation Hybrid Mapping , Swine/genetics , Amino Acid Sequence , Animals , Binding Sites , Cloning, Molecular , Conserved Sequence , DNA Primers , Factor V/metabolism , Humans , Models, Molecular , Molecular Sequence Data , Protein Structure, Secondary , Protein Structure, Tertiary , Sequence Homology, Amino Acid
4.
Chest ; 118(5): 1397-404, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11083692

ABSTRACT

OBJECTIVES: We administered aerosolized histamine to 32 subjects with tetraplegia to determine whether there were differences in spirometric and/or lung volume parameters between responders and nonresponders. RESULTS: Baseline pulmonary function parameters revealed mild to moderate restrictive dysfunction. We found that 25 subjects (78%) were hyperreactive to histamine (mean provocative concentration of a substance causing a 20% fall in FEV(1) [PC(20)], 1.77 mg/mL). Responders (PC(20), < 8 mg/mL) had significantly lower values for forced expiratory flow between 25% and 75% of the outflow curve (FEF(25-75)), FEF(25-75) percent predicted, and FEF(25-75)/FVC ratio. Among all 32 subjects, the natural logarithmic transformation performed on PC(20) values (lnPC(20)) correlated with FEF(25-75) percent predicted, FEV(1) percent predicted, and FEF(25-75)/FVC ratio but not with FVC percent predicted. Responders with PC(20) values < 2 mg/mL (n = 13) had significantly reduced values for FVC, FVC percent predicted, FEV(1), and FEV(1) percent predicted compared to those with PC(20) values between 2 mg/mL and 8 mg/mL. In addition, among responders, there was a significant correlation between lnPC(20) and FVC percent predicted. A significant relationship was found between maximal inspiratory pressure (PImax) and both FEV(1) percent predicted and FEF(25-75) percent predicted, but not between lnPC(20) and either PImax or maximal expiratory pressure (PEmax). CONCLUSIONS: These findings demonstrate that subjects with tetraplegia who exhibit airway hyperreactivity (AHR) have reduced baseline airway caliber and that lower values for lnPC(20) are associated with parallel reductions in surrogate spirometric indexes of airway size (FEV(1) percent predicted and FEF(25-75) percent predicted) and airway size relative to lung size (FEF(25-75)/FVC ratio). The absence of an association between lnPC(20) and FVC percent predicted for the entire group or between lnPC(20) and either PImax or PEmax indicates that reduced lung volumes secondary to respiratory muscle weakness cannot explain the mechanism(s) underlying AHR. Among responders, however, a possible role for reduction in lung volume, as it pertains to increasing AHR, cannot be excluded. Proposed mechanisms for reduced baseline airway caliber relative to lung size in subjects with tetraplegia include unopposed parasympathetic activity secondary to the loss of sympathetic innervation to the lungs and/or the inability to stretch airway smooth muscle with deep inhalation.


Subject(s)
Bronchial Hyperreactivity/physiopathology , Lung/pathology , Quadriplegia/physiopathology , Adult , Aerosols , Aged , Bronchial Provocation Tests , Bronchoconstrictor Agents/administration & dosage , Dose-Response Relationship, Drug , Forced Expiratory Volume/physiology , Histamine/administration & dosage , Humans , Inhalation/physiology , Linear Models , Lung/innervation , Lung/physiopathology , Maximal Expiratory Flow Rate/physiology , Maximal Midexpiratory Flow Rate/physiology , Middle Aged , Muscle, Smooth/physiopathology , Pressure , Pulmonary Ventilation/physiology , Respiratory Muscles/physiopathology , Spirometry , Vital Capacity/physiology
5.
Arch Phys Med Rehabil ; 81(7): 921-3, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10896005

ABSTRACT

OBJECTIVE: To determine the effect of the GABA-agonist baclofen on cough reflex sensitivity in subjects with cervical spinal cord injury (C-SCI). Baclofen has been shown to inhibit the cough reflex in able-bodied volunteers. DESIGN: Prospective, nonrandomized control trial. SETTING: Veterans Affairs medical center with large outpatient SCI population. PARTICIPANTS: Twelve adult males (11 outpatients) with C-SCI chronically maintained on oral baclofen for the treatment of muscle spasm. INTERVENTION: Subjects underwent cough challenge testing with inhaled capsaicin. The concentrations (microM) of capsaicin inducing 2 or more (C2) and 5 or more (C5) coughs were determined. Mean values for log C2 and log C5 were compared with a control group of outpatients with C-SCI not receiving baclofen. RESULTS: Subjects treated with baclofen had a significantly higher cough threshold (diminished cough reflex sensitivity) than control subjects. Mean (+/- standard error of the mean) values for log C2 in study subjects and controls were 1.28 +/- .16 and .65 +/- .15, respectively (p = .009). Mean values for log C5 in subjects receiving baclofen and in control subjects were 2.20 +/- .22 and 1.43 +/- .23, respectively (p = .024). Subjects and controls did not differ in terms of age, spirometric parameters, or duration of injury. CONCLUSIONS: The results suggest that chronic therapy with baclofen diminishes cough reflex sensitivity in subjects with C-SCI. The clinical significance of this finding remains to be elucidated.


Subject(s)
Baclofen/pharmacology , Cough/physiopathology , GABA Agonists/pharmacology , Reflex/drug effects , Spinal Cord Injuries/physiopathology , Adult , Humans , Male , Middle Aged , Prospective Studies
6.
Am J Physiol Heart Circ Physiol ; 278(2): H515-20, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10666083

ABSTRACT

The effects of autonomic disruption and inactivity were studied on the venous vascular system. Forty-eight subjects, 24 with spinal cord injury (SCI) and 12 sedentary and 12 active able-bodied controls, participated in this study. Peripheral autonomic data were obtained to estimate sympathetic vasomotor control [low-frequency component of systolic blood pressure (LF(SBP))]. Vascular parameters were determined using strain-gauge venous occlusion plethysmography: venous capacitance (VC), venous emptying rate (VER), and total venous outflow (VO(t)). An additional vascular parameter was calculated: venous compliance [(VC/occlusion pressure) x 100]. VC and VO(t) were significantly different (SCI < sedentary < active). VER adjusted for VC was not different for any group comparison, whereas venous compliance was significantly lower in the SCI group than in the able-bodied groups and in the sedentary group compared with the active group. Regression analysis for the total group revealed a significant relationship between LF(SBP) and venous compliance (r = 0.64, P < 0.0001). After controlling for LF(SBP) through analysis of covariance, we found that mean differences for all venous vascular parameters did not change from unadjusted mean values. Our findings suggest that in subjects with SCI, the loss of sympathetic vasomotor tone contributes more than inactivity to reductions in venous vascular function. Heightened VC, VO(t), vasomotor tone, and venous compliance in the active group compared with the sedentary group imply that regular endurance training contributes to optimal venous vascular function and peripheral autonomic integrity.


Subject(s)
Autonomic Nervous System Diseases/physiopathology , Veins/physiopathology , Adult , Compliance , Female , Humans , Male , Middle Aged , Paraplegia/physiopathology , Physical Fitness , Quadriplegia/physiopathology , Reference Values , Sympathetic Nervous System/physiopathology , Vasomotor System/physiopathology
7.
Biochim Biophys Acta ; 1446(3): 193-202, 1999 Sep 03.
Article in English | MEDLINE | ID: mdl-10524194

ABSTRACT

Cartilage is a tissue that is primarily extracellular matrix, the bulk of which consists of proteoglycan aggregates constrained within a collagen framework. Candidate components that organize the extracellular assembly of the matrix consist of collagens, proteoglycans and multimeric glycoproteins. We describe the human gene structure of a potential organizing factor, a cartilage-derived member of the C-type lectin superfamily (CLECSF1; C-type lectin superfamily) related to the serum protein, tetranectin. We show by Northern analysis that this protein is restricted to cartilage and locate the gene on chromosome 16q23. We have characterized 10.9 kb of sequence upstream of the first exon. Similarly to human tetranectin, there are three exons. The residues that are conserved between CLECSF1 and tetranectin suggest that the cartilage-derived protein forms a trimeric structure similar to that of tetranectin, with three N-terminal alpha-helical domains aggregating through hydrophobic faces. The globular, C-terminal domain that has been shown to bind carbohydrate in some members of the family and plasminogen in tetranectin, is likely to have a similar overall structure to that of tetranectin.


Subject(s)
Collagen/metabolism , Glycoproteins/genetics , Lectins, C-Type , Lectins/genetics , Amino Acid Sequence , Base Sequence , Blood Proteins/genetics , Chromosome Mapping , Exons , Gene Library , Glycoproteins/chemistry , Humans , In Situ Hybridization, Fluorescence , Molecular Sequence Data , Polymerase Chain Reaction , Sequence Alignment
8.
Anim Genet ; 30(4): 251-5, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10467699

ABSTRACT

To develop additional microsatellite (MS) markers in the region of the porcine skeletal muscle ryanodine receptor gene (RYR1), a microdissected genomic library was generated from the proximal half of the q arm of swine chromosome 6. Purified DNA was restriction enzyme-digested, ligated to oligonucleotide adaptors and amplified by PCR using primers complementary to the adaptor sequences. The purity of the amplified products and boundaries of the microdissected chromosomal region were verified by fluorescence in situ hybridization. (CA)n-containing sequences were then identified in a small insert genomic library generated from the PCR-amplified microdissected DNA. Oligonucleotide primers were developed for the PCR amplification of 30 of the 46 (CA)n repeat-containing clones, which were subsequently used to amplify DNA isolated from unrelated pigs of different breeds to determine the informativeness of these MS markers. Twenty-two of these MS markers were genotyped on the University of Illinois Yorkshire x Meishan swine reference population. These 22 markers were all assigned within a 50.7-CM region of the swine chromosome 6 linkage map, indicating the specificity of the microdissected library.


Subject(s)
Genomic Library , Microsatellite Repeats , Swine/genetics , Animals , Base Sequence , Chromosome Mapping , Chromosomes/genetics , DNA Primers/genetics , Genetic Linkage , Genotype , Polymerase Chain Reaction , Polymorphism, Genetic , Ryanodine Receptor Calcium Release Channel/genetics
10.
Mt Sinai J Med ; 66(3): 201-5, 1999 May.
Article in English | MEDLINE | ID: mdl-10377553

ABSTRACT

BACKGROUND: Pulmonary complications are a major cause of morbidity and mortality among individuals with cervical spinal cord lesions. Strengthening of the respiratory musculature may reduce these complications. Anabolic steroids have been used to increase muscle mass and improve muscle performance. Oxandrolone, an anabolic steroid, may have beneficial effects on breathing in persons with tetraplegia. METHODS: The effect of one-month treatment with oxandrolone on weight gain and pulmonary function was studied in ten subjects with complete motor tetraplegia. Spirometry, maximal inspiratory and expiratory pressures, and resting self-rating of dyspnea (Borg Scale) were measured at baseline and repeated again at the end of one month of oxandrolone therapy (20 mg/day). Serum lipid profiles and liver function tests were performed before and after treatment. A paired t-test was used to determine pre- and post-treatment differences on the dependent variables. Percent change from baseline was calculated for each variable and tested using a one-sample t-test. RESULTS: On average, the subjects gained 1.4+/-1.5 kg, a 2+/-2% increase in weight (p=0.01). A significant, 9+/-2% improvement was found in the combined measures of spirometry (p<0.005). Maximal inspiratory pressure improved an average of 10+/-7% (p<0.001). Maximal expiratory pressure improved 9+/-13% (non-significant). Subjective self-rating of dyspnea decreased an average of 37+/-28% (p<0.01). CONCLUSIONS: In healthy subjects with tetraplegia, the use of oxandrolone was associated with significant improvements in weight and pulmonary function, and a subjective reduction in breathlessness. Therefore, oxandrolone may be indicated to strengthen respiratory musculature in individuals who have tetraplegia and ventilatory insufficiency aggravated by superimposition of pneumonia or other such conditions. However, long-term use of oxandrolone may not be indicated, due to the adverse complications associated with this class of agents.


Subject(s)
Anabolic Agents/therapeutic use , Dyspnea/drug therapy , Oxandrolone/therapeutic use , Quadriplegia/complications , Body Weight/drug effects , Humans , Male , Pilot Projects
11.
Chest ; 115(6): 1533-8, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10378545

ABSTRACT

STUDY OBJECTIVE: Aerosolized ipratropium bromide or orally administered baclofen or oxybutynin chloride (Ditropan) block methacholine-associated airway hyperreactivity in subjects with chronic cervical spinal cord injury (SCI), whereas these agents do not inhibit airway hyperreactivity associated with the inhalation of histamine. The present study was performed to determine whether pretreatment with a beta2-agonist attenuates airway hyperresponsiveness in these subjects. PARTICIPANTS: Subjects with chronic cervical SCI previously demonstrating airway hyperreactivity were challenged with methacholine (n = 9) or histamine (n = 16) alone and, on a separate day, 25 min following inhalation of nebulized metaproterenol sulfate. RESULTS: Inhalation of the beta2-agonist was associated with an increase in provocative concentration causing a 20% decrease in FEV1 (PC20) values (geometric mean) from 1.01+/-2.76 to 20.54+/-6.24 mg/mL for methacholine and from 2.29+/-2.26 to 19.82+/-5.93 mg/mL for histamine. No correlation was found between specific PC20 values for individual subjects and percentage improvement in FEV1 (liter) following inhalation of metaproterenol sulfate and between PC20 values and baseline FEV1 percent. CONCLUSION: These data, combined with findings that patients with chronic high cervical SCI experience increased breathlessness following exposure to exogenous agents, suggest that long-term prophylactic beta2-agonist therapy may reduce respiratory symptoms associated with airway hyperreactivity in these patients.


Subject(s)
Adrenergic beta-Agonists/therapeutic use , Bronchial Hyperreactivity/physiopathology , Metaproterenol/therapeutic use , Spinal Cord Injuries/physiopathology , Administration, Inhalation , Adrenergic beta-Agonists/administration & dosage , Adult , Aged , Bronchial Hyperreactivity/diagnosis , Bronchial Hyperreactivity/drug therapy , Bronchial Provocation Tests , Bronchoconstriction/drug effects , Chronic Disease , Follow-Up Studies , Forced Expiratory Volume , Histamine , Humans , Metaproterenol/administration & dosage , Methacholine Chloride , Middle Aged , Nebulizers and Vaporizers , Neck , Respiratory Function Tests , Spinal Cord Injuries/drug therapy , Treatment Outcome
12.
Spinal Cord ; 37(4): 279-83, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10338349

ABSTRACT

OBJECTIVE: To further investigate mechanisms of airway hyperreactivity among subjects with chronic cervical spinal cord injury (SCI), we assessed airway responsiveness to aerosolized methacholine and histamine in subjects receiving chronic oxybutynin chloride therapy, and compared the findings with those not receiving the agent. METHODS: Twenty-five male subjects with cervical SCI participated in this study; 12 were maintained on oral oxybutynin chloride and 13 served as age-matched controls. Six of the 12 subjects receiving oxybutynin were challenged with aerosolized methacholine, and six with histamine; seven of the 13 control subjects were challenged with aerosolized methacholine and the remaining six with histamine. RESULTS: All 13 control subjects and all six oxybutynin/histamine subjects exhibited a significant bronchoconstrictor response (PC20 < 8 mg/ml), whereas mean PC20 values for the oxybutynin/methacholine group were > or =25 mg/ml. CONCLUSION: Our finding that the bronchoconstrictor effects of methacholine were blocked by oxybutynin chloride while those of histamine were not suggests that oxybutynin acts primarily through anticholinergic pathways rather than by causing generalized airway smooth muscle relaxation.


Subject(s)
Bronchial Hyperreactivity/drug therapy , Cholinergic Antagonists/therapeutic use , Mandelic Acids/therapeutic use , Spinal Cord Injuries/complications , Adult , Aerosols , Bronchial Hyperreactivity/etiology , Bronchial Hyperreactivity/prevention & control , Bronchodilator Agents/administration & dosage , Histamine/administration & dosage , Humans , Male , Methacholine Chloride/administration & dosage , Middle Aged , Spirometry
13.
Am J Respir Crit Care Med ; 159(5 Pt 1): 1660-2, 1999 May.
Article in English | MEDLINE | ID: mdl-10228141

ABSTRACT

An effective cough requires an intact cough reflex as well as adequate respiratory muscle function to generate elevated intrathoracic pressures. Since the major muscles of expiration are innervated by the first thoracic segment and below, transection of the cervical spinal cord results in severely compromised expiratory function and cough. To investigate the effects of cervical spinal cord injury (C-SCI) on cough reflex sensitivity, we measured responsiveness to inhaled capsaicin in 12 male subjects with chronic C-SCI and compared findings to those from a control group of 50 able-bodied men. The concentrations (microM) of capsaicin inducing two or more (C2) and five or more coughs (C5) did not significantly differ between the two groups. Mean (+/- SEM) values for log C2 in subjects with C-SCI and control subjects were 0.65 +/- 0.15 and 0.87 +/- 0.07, respectively (p = 0.15). Mean values for log C5 in subjects with C-SCI and control subjects were 1.43 +/- 0.23 and 1.41 +/- 0.08, respectively (p = 0.94). We conclude that cough reflex sensitivity is preserved after C-SCI, and that ineffective cough in this population results primarily from the loss of innervation of respiratory muscles.


Subject(s)
Cough/physiopathology , Reflex/physiology , Spinal Cord Injuries/physiopathology , Adult , Aged , Capsaicin , Cough/chemically induced , Forced Expiratory Volume/physiology , Humans , Male , Middle Aged , Neck , Reference Values
14.
J Appl Physiol (1985) ; 86(4): 1165-9, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10194198

ABSTRACT

The majority of otherwise healthy subjects with chronic cervical spinal cord injury (SCI) demonstrate airway hyperresponsiveness to aerosolized methacholine or histamine. The present study was performed to determine whether ultrasonically nebulized distilled water (UNDW) induces airway hyperresponsiveness and to further elucidate potential mechanisms in this population. Fifteen subjects with SCI, nine with tetraplegia (C4-7) and six with paraplegia (T9-L1), were initially exposed to UNDW for 30 s; spirometry was performed immediately and again 2 min after exposure. The challenge continued by progressively increasing exposure time until the forced expiratory volume in 1 s decreased 20% or more from baseline (PD20) or the maximal exposure time was reached. Five subjects responding to UNDW returned for a second challenge 30 min after inhalation of aerosolized ipratropium bromide (2.5 ml of a 0.6% solution). Eight of nine subjects with tetraplegia had significant bronchoconstrictor responses to UNDW (geometric mean PD20 = 7.76 +/- 7.67 ml), whereas none with paraplegia demonstrated a response (geometric mean PD20 = 24 ml). Five of the subjects with tetraplegia who initially responded to distilled water (geometric mean PD20 = 5.99 +/- 4.47 ml) were not responsive after pretreatment with ipratropium bromide (geometric mean PD20 = 24 ml). Findings that subjects with tetraplegia are hyperreactive to UNDW, a physicochemical agent, combined with previous observations of hyperreactivity to methacholine and histamine, suggest that overall airway hyperresponsiveness in these individuals is a nonspecific phenomenon similar to that observed in patients with asthma. The ability of ipratropium bromide to completely block UNDW-induced bronchoconstriction suggests that, in part, airway hyperresponsiveness in subjects with tetraplegia represents unopposed parasympathetic activity.


Subject(s)
Paraplegia/physiopathology , Quadriplegia/physiopathology , Respiratory Mechanics/physiology , Spinal Cord Injuries/physiopathology , Water/pharmacology , Adult , Aerosols , Bronchoconstriction/drug effects , Bronchoconstriction/physiology , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/pharmacology , Humans , Ipratropium/administration & dosage , Ipratropium/pharmacology , Male , Nebulizers and Vaporizers , Paraplegia/etiology , Quadriplegia/etiology , Smoking , Spirometry , Ultrasonics , Water/administration & dosage
15.
J Rehabil Res Dev ; 36(3): 202-6, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10659803

ABSTRACT

This study compared transcutaneous oxygen tension (TcpO2) in subjects with paraplegia and pressure ulcers (PU), those with paraplegia and no pressure ulcer (NPU), and ambulatory controls. TcpO2 was measured using a surface-electrode monitoring system, recorded at 1-min intervals for 5 min and averaged. Mean TcpO2 was significantly lower in the PU than the NPU and control groups (23.53+/-1.83 vs. 58.93+/-2.53 and 79.70+/-6.77 mmHg, respectively, p<0.05). In a PU subgroup (n=4) mean TcpO2 of the pressure ulcer and nonpressure ulcer sides (trochanter or ischium) were significantly different (21.05+/-2.98 vs. 67.65+/-2.11 mmHg, respectively, p<0.001). Additionally, the NPU group demonstrated significantly lower TcpO2 than the controls. PUs had a greater reduction in TcpO2 levels relative to controls than NPUs. No association was found between TcpO2 and duration of injury, completeness of lesion, or smoking history. Thus, TcpO2 may be an effective method to identify individuals who are susceptible to pressure ulcers. The further attenuation of TcpO2 observed in the PU group may be useful to help predict whether ulcers will heal with local care or will require additional treatment.


Subject(s)
Blood Gas Monitoring, Transcutaneous/methods , Oxygen/blood , Pressure Ulcer/etiology , Quadriplegia/complications , Quadriplegia/metabolism , Adult , Aged , Analysis of Variance , Biomarkers , Blood Gas Monitoring, Transcutaneous/instrumentation , Body Surface Area , Case-Control Studies , Disease Susceptibility , Humans , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Time Factors , Wound Healing
16.
Anim Genet ; 29(1): 43-7, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9682450

ABSTRACT

The present report describes the isolation and genetic characterization of the porcine apolipoprotein E (apo-E) gene. A single positive recombinant phage clone containing a 10.7-kb insert was isolated from a porcine genomic library, and a 4.2-kb fragment was subcloned and sequenced. The 4.2-kb fragment contained the entire apo-E gene in addition to upstream and downstream sequences (GenBank accession no. 470240). The porcine apo-E gene is made up of four exons and three introns, and encodes a preapo-E protein comprised of a signal peptide of 18 amino acids and a mature protein of 299 amino acids. The porcine apo-E gene contains a (CG)13 microsatellite marker within intron three. This microsatellite is moderately polymorphic, and at least four alleles were evident at this locus among 10 animals from each of the Yorkshire, Hampshire, Landrace and Duroc breeds. Finally, localization of the porcine apo-E gene to chromosome 6 band q2.1 was determined by fluorescent in situ hybridization and confirmed by genetic linkage analysis.


Subject(s)
Apolipoproteins E/genetics , Chromosome Mapping/veterinary , Restriction Mapping/veterinary , Swine/genetics , Animals , Apolipoproteins E/chemistry , Apolipoproteins E/isolation & purification , Base Sequence , Cloning, Molecular , DNA Primers , Disease Models, Animal , Exons/genetics , Gene Frequency , In Situ Hybridization, Fluorescence/veterinary , Introns/genetics , Microsatellite Repeats/genetics , Molecular Sequence Data , Protein Sorting Signals/genetics , Sequence Analysis, DNA/veterinary , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid
17.
Clin Auton Res ; 8(2): 111-8, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9613801

ABSTRACT

Due to the increased prevalence of ischemic heart disease and hypertension reported in individuals with chronic spinal cord injury (SCI), we investigated whether subjects with low level SCI (paraplegia), without apparent evidence of coronary artery disease, exhibit normal baroreceptor and autonomic function. Eighteen males participated in this study: seven normotensive with paraplegia, five hypertensive with paraplegia and six normotensive non-SCI controls. The Valsalva maneuver was performed by maintaining a pressure of 40 mmHg over 15 s and R-R intervals (RRI) and arterial blood pressure were measured continuously. Phase IV of the Valsalva maneuver was determined by linear regression analysis between RRI and systolic pressure, with a final slope calculated. The power spectra for RRI and blood pressure variability parameters were also analyzed, in addition to the index alpha, a frequency domain estimate of the overall gain in baroreceptor control of the RRI-arterial blood pressure. The normotensive subjects with paraplegia were found to have an impaired baroreceptor response when compared with age-matched, non-SCI controls. In addition, the levels of both the low frequency and high frequency spectral components of RRI and the index alpha were reduced in these individuals at rest. These cumulative findings strongly suggest that the integrity of the sinoaortic baroreceptors, as well as efferent parasympathetic function, may be compromised in otherwise apparently healthy individuals with chronic paraplegia.


Subject(s)
Pressoreceptors/physiopathology , Spinal Cord Injuries/physiopathology , Valsalva Maneuver , Adult , Humans , Hypertension/complications , Hypertension/physiopathology , Male , Middle Aged , Paraplegia/complications , Paraplegia/physiopathology , Reference Values , Sinus of Valsalva/physiopathology , Spinal Cord Injuries/complications
18.
Arch Phys Med Rehabil ; 79(3): 293-7, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9523781

ABSTRACT

OBJECTIVE: To determine whether pulmonary function, respiratory muscle strength, and dyspnea can be improved in individuals with chronic cervical spinal cord injury (SCI). STUDY DESIGN: Ten subjects participated in an 8-week resistive inspiratory muscle training (IMT) program for 15 minutes twice daily. Spirometry, lung volumes, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and dyspnea were measured at baseline, week 4, and week 8. Six months after the study, spirometry, MIP, and MEP were re-measured in a subgroup of the original participants. RESULTS: We found that regular IMT in subjects with cervical SCI significantly improved forced vital capacity (means +/- SE) (11% +/- 2.82% increase), forced inspiratory vital capacity (21% +/- 6.91%), vital capacity (8% +/- 4.36%), total lung capacity (12% +/- 3.23%), functional residual capacity (15% +/- 5.96%), and MIP (24% +/- 6.98%) (p < .05). Furthermore, although no statistical differences were observed for the dyspnea scale, the fact that subjects reported decreased levels (43% +/- 21.30% reduction) of perceived difficulty breathing may be of greater importance. No significant differences from baseline values were found in the seven subjects whose spirometry and respiratory muscle strength were measured 6 months after the study. CONCLUSIONS: Our findings suggest that in individuals with cervical SCI regular resistive IMT may result in decreased restrictive ventilatory impairment and reported dyspnea and, thus, reduced incidence of chronic respiratory complaints, respiratory infection, and other pulmonary complications.


Subject(s)
Breathing Exercises , Dyspnea/rehabilitation , Respiratory Muscles/physiopathology , Spinal Cord Injuries/physiopathology , Adult , Aged , Chronic Disease , Dyspnea/etiology , Dyspnea/physiopathology , Exercise Therapy , Humans , Male , Respiratory Function Tests , Spinal Cord Injuries/complications , Treatment Outcome
19.
J Asthma ; 35(1): 49-55, 1998.
Article in English | MEDLINE | ID: mdl-9513582

ABSTRACT

Previously, we reported that a majority of subjects with chronic cervical spinal cord injury (SCI) demonstrated airway hyperreactivity in response to inhaled methacholine. To further investigate mechanisms of airway hyperreactivity, 15 male subjects with cervical SCI were challenged with aerosolized histamine, and on a separate day responders were rechallenged 30 min after the inhalation of 72 micrograms of ipratropium bromide. Twelve of 15 subjects demonstrated airway hyperresponsiveness to histamine (geometric mean PC20 of 1.27 mg/ml), which was not blocked by pretreatment with ipratropium bromide (geometric mean PC20 1.50 mg/ml). Baseline forced vital capacity and forced expiratory volume in 1 sec were not significantly different between responders and nonresponders (2.8 +/- 0.6 vs. 3.0 +/- 0.4 L and 2.3 +/- 0.6 vs. 2.4 +/- 0.2 L, respectively). Findings that subjects with cervical SCI are hyperresponsive to methacholine and histamine, chemical agents with direct action through distinct receptor systems, suggest that bronchial hyperreactivity in these subjects represents a nonspecific process similar to that observed in patients with asthma.


Subject(s)
Bronchial Hyperreactivity/physiopathology , Bronchoconstriction/drug effects , Ipratropium/pharmacology , Muscarinic Antagonists/pharmacology , Spinal Cord Injuries/physiopathology , Adult , Bronchial Provocation Tests , Bronchoconstriction/physiology , Histamine , Humans , Male , Middle Aged , Spirometry
20.
Spinal Cord ; 35(10): 652-7, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9347593

ABSTRACT

To determine the prevalence of respiratory symptoms in subjects with chronic spinal cord injury (SCI), 180 subjects completed a standard respiratory questionnaire modified for subjects with limited mobility. Subjects were categorized as high tetraplegia (HT:C5 and above not requiring mechanical ventilation), low tetraplegia (LT: C6-8), high paraplegia (HP: T1-7), or low paraplegia (LP: T8-L3). Overall, 68% of subjects reported one or more respiratory symptom. Breathlessness, the most prevalent complaint, was associated with level of lesion: HT = 73%, LT = 58%, HP = 43% and LP = 29%, whereas complaints of cough, phlegm, cough and phlegm, and wheeze did not differ significantly among subjects in the four groups. Breathlessness occurred significantly more often in the group with HT during rest or following exposure to hot air or passive smoke. Awareness of phlegm or wheeze was reported with increased prevalence among subjects with tetraplegia who had complete injuries. Among subjects with tetraplegia, respiratory complaints did not differ significantly in current smokers, former smokers, and non-smokers, whereas among subjects with paraplegia, phlegm and wheeze were reported more frequently, among current smokers.


Subject(s)
Respiratory Tract Diseases/epidemiology , Smoking/adverse effects , Spinal Cord Injuries/complications , Adult , Analysis of Variance , Chi-Square Distribution , Follow-Up Studies , Humans , Male , Middle Aged , Paraplegia/complications , Prevalence , Quadriplegia/complications , Respiratory Tract Diseases/etiology , Risk Factors , Surveys and Questionnaires
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