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J E Butler

Publications and source records attributed to J E Butler.

At least 73 records · Page 4Linked to original sources
PubMed1997

Pulmonary afferents are not necessary for the reflex inhibition of human inspiratory muscles produced by airway occlusion.

In contrast to limb muscles, the usual response of human inspiratory muscles to sudden loading consists of an initial marked reduction of electromyographic activity (EMG) followed by a subsequent increase in EMG. To determine definitively whether pulmonary receptors are necessary for this short-latency reflex inhibition produced by airway occlusion, we studied five subjects with complete pulmonary denervation due to bilateral transplantation of the lungs and five matched control subjects. Subjects with pulmonary denervation were studied between 10 and 50 days after transplantation (median 21 days). Brief airway occlusion during inspiration (i.e., loading; duration 250 ms) produced short-latency reduction in EMG in the inspiratory muscles of all subjects with acute pulmonary denervation (scalenes and parasternal intercostal muscles; mean onset of inhibition 27 and 29 ms, respectively). The ongoing EMG was reduced by an average of 50% in scalenes and 36% in parasternal intercostal muscles. The size and the magnitude of the initial response did not differ significantly from those in control subjects. After the occlusion (i.e., unloading), activity of the inspiratory muscles was transiently reduced in control subjects and patients after bilateral lung transplantation. Given that the initial responses to airway loading and unloading were preserved after bilateral lung transplantation, we conclude that these reflex responses are not critically dependent on the discharge of intrapulmonary receptors. The results support the view that the short-latency inspiratory responses to loading and unloading can be mediated by inspiratory muscle afferents. They suggest a functionally different organization of the reflex pathways for inspiratory compared with limb muscles.

Adolescent↗
PubMed1997

Genetic association between parameters of inmate immunity and measures of mastitis in periparturient Holstein cattle.

Relationships between genetic measures of mastitis (somatic cell score, score for clinical mastitis, and scores for IMI with major or minor pathogens) and immunological parameters (physiological and molecular markers) were examined for periparturient Holstein cows. Physiological markers included 11 in vitro immunological assays. Molecular markers included the second exon of the DRB3 locus of the bovine major histocompatibility complex, the IgG2 isotype genotype, and the CD18 genotype (the locus responsible for bovine leukocyte adhesion deficiency). A gene substitution model was used to estimate the additive genetic effects of alleles of the three molecular markers on estimated breeding value (EBV) for mastitis measures. Pearson correlation coefficients between EBV for immunological assays and EBV for mastitis measures were computed. Molecular markers explained up to 40% of the variation in EBV for measures of mastitis. The presence of allele DRB3.2*16 was associated with higher EBV for SCS. Allele DRB3.2*8 was associated with increased EBV for clinical mastitis, as was the IgG2b allele and the normal CD18 allele. Alleles DRB3.2*11, *23, IgG2a, and the recessive allele for bovine leukocyte adhesion deficiency were associated with decreased clinical mastitis. A positive genetic association was found between allele DRB3.2*24 and EBV for IMI by major pathogens and between DRB3.2*3 and IMI by minor pathogens. Several correlations between EBV for immunological assays and EBV for mastitis measures were significantly different from 0. Cows with low EBV for SCS tended to have neutrophils that had greater functional ability at maximal immunosuppression, low serum IgG1, and high numbers of circulating mononuclear cells. Immunological parameters, including physiological and molecular markers, are useful aids to understand the genetics of resistance to mastitis.

Alleles↗
PubMed1997

Bovine IgG2a antibodies to Haemophilus somnus and allotype expression.

Bovine IgG2a has been implicated in protection against pyogenic infections, including those caused by Haemophilus somnus. To further investigate the role of IgG2a in defense against H. somnus, IgG1 and IgG2a antibodies were purified from antiserum against an immunodominant 40 kDa outer membrane protein (p40) of H. somnus, which was previously shown to passively protect calves against H. somnus pneumonia. The passive protective capacity of anti-p40 IgG1 or IgG2a was evaluated in vivo in calves. Purified anti-p40 IgG1 or IgG2a was incubated with H. somnus for 15 min before intrabronchial inoculation of calves. Bacteria incubated with anti-p40 IgG1 or IgG2a were inoculated into one caudal lung lobe and bacteria incubated with IgG1 or IgG2a from the respective preimmunization serum were inoculated into the contralateral lobe. The volumes of pneumonia in the right and left lungs were determined 24 h later. The difference in volume of pneumonia with H. somnus preincubated in IgG1 pre- and postimmunization anti p40 was less (16 cm3, P = 0.298) than the difference in volume of pneumonia with H. somnus preincubated in IgG2a pre- and postimmunization anti p40 (30 cm3, P = 0.146). Although the differences in lesion size between pre- and postimmunization serum were not statistically significant, the trend suggests IgG2a may be more protective than IgG1. To examine this further, the peptide specificity of these IgG1 and IgG2a antibodies to p40 was examined. After limited proteolysis of p40, IgG2a antibodies reacted with 2 peptides not recognized by IgG1 antibodies. Other peptides were recognized by both isotypes. Since these studies suggested that IgG2a may be important in protection against infection, we then investigated some aspects of the role of the 2 IgG2a allotypes, A1 and A2. In retrospective studies of age differences in expression of IgG2a allotypes, no heterozygotes were detected in calves of 60 d old or less, and fewer heterozygotes were detected in calves 61-120 d old than in cattle older than 270 d (P < 0.01). In a subsequent prospective study of the time course of allotype expression, Holstein calves shown to be heterozygotes expressed the IgG2aA1 allotype early but the IgG2aA2 allotype was not usually detected until 3 to 4 mo of age. Thus, both the retrospective and the prospective studies showed age related differences in expression of the IgG2aA1 and A2 allotypes. This could have implication in protection.

Age Factors↗
PubMed1996

Changes in motor cortical excitability during human muscle fatigue.

1. The excitability of the motor cortex was investigated during fatiguing con of the elbow flexors in human subjects. During sustained contractions at 30 and 1 voluntary force (MVC), the short-latency electromyographic responses (EMG) evoke brachii and brachioradialis by transcranial magnetic stimulation increased in si EMG in the elbow flexors following the evoked muscle potential (silent period), duration during a sustained MVC but not during 30% MVCs nor during a sustained M muscle (adductor pollicis). 2. When the blood supply to brachioradialis was blocked with sphygmomanometer cuff sustained MVC, the changes in EMG responses to transcranial stimulation rapidly control values, This suggests that changes in these responses during fatigue wer small-diameter muscle afferents. 3. Tendon vibration during sustained MVCs indicated that the changes in the resp cortial stimulation were not mediated by reduced muscle spindle inputs. 4. Muscle action potentials evoked in brachioradialis by electrical stimulation cervicomedullary junction did not increase in size during sustained MVCs. Thus, cortically evoked responses during sustained MVCs reflects a change in cortical Although the silent period following cervicomedullary stimulation lengthened, it substantially shorter than the cortically evoked silent period. 5. The altered EMG responses to transcranial stimulation during fatigue suggest exitation and increased inhibition in the motor cortex. As these changes were un manipulation of afferent input they presumably result from intrinsic cortical pr altered voluntary drive to the motor cortex.

Action Potentials↗
PubMed1996

Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex.

1. Voluntary activation of elbow flexor muscles can be optimal during brief maximal voluntary contractions (MVCs), although central fatigue, a progressive decline in the ability to drive the muscle maximally, develops during sustained or repeated efforts. We stimulated the motor cortex and motor point in human subjects to investigate motor output during fatigue. 2. The increment in force (relative to the voluntary force) produced by stimulation of the motor point of biceps brachii increased during sustained isometric MVCs of the elbow flexors. Motoneuronal output became suboptimal during the contraction, i.e. central fatigue developed and accounted for a small but significant loss of maximal voluntary force. During 3 min MVCs, voluntary activation of biceps fell to an average of 90.7% from an average of > 99%. 3. The increment in force (relative to the voluntary force) produced by magnetic cortical stimulation was initially small (1.0%) but also increased during sustained MVCs to 9.8% (with a 2 min MVC). Thus, cortical output was not optimal at the time of stimulation nor were sites distal to the motor cortex already acting maximally. 4. A sphygmomanometer cuff around the upper arm blocked blood supply to brachioradialis near the end of a sustained MVC and throughout subsequent brief MVCs. Neither maximal voluntary force nor voluntary activation recovered during ischaemia after the sustained MVC. However, fatigue-induced changes in EMG responses to magnetic cortical stimulation recovered rapidly despite maintained ischaemia. 5. In conclusion, during sustained MVCs, voluntary activation becomes less than optimal so that force can be increased by stimulation of the motor cortex or the motor nerve. Complex changes in excitability of the motor cortex also occur with fatigue, but can be dissociated from the impairment of voluntary activation. We argue that inadequate neural drive effectively 'upstream' of the motor cortex must be one site involved in the genesis of central fatigue.

Adult↗
PubMed1996

The heterogeneity of bovine IgG2--VIII. The complete cDNA sequence of bovine IgG2a (A2) and an IgG1.

The complete cDNA sequences of two bovine IgGs were obtained by RT-PCR cloning. The first-strand cDNA was prepared from an animal homozygous (A2/A2) for IgG2a; the resulting sequences of the two bovine IgGs reported here were identified as IgG2a(A2) and IgG1. These sequences, and their deduced amino acid sequences, are compared to the previously reported partial protein sequences of IgG2a(A2) and IgG2(A1), two genomic DNA sequences of IgG2a and one genomic DNA sequence of IgG1. Data show that the two IgG2a allotypes (A1 and A2) differ in four regions: (a) region I-the site of the L-H bond in CH1; (b) region II-the middle hinge; (c) region III-a seven amino acid region at the beginning of the intradomain loop in CH3; and (d) region IV-an Arg-to-Glu exchange at the end of the same intradomain loop. The A1 allotype, which so remarkably distinguishes these allotypic variants, must result from differences in regions III and IV. The IgG1 sequence differs in the hinge region from the sequence reported previously and may represent an allotypic variant. We found no evidence to support the hypothesis that similarities between the CH3 domains of IgG2a(A2) and IgG1 result from gene conversion in the C-region of the bovine heavy chain locus.

Amino Acid Sequence↗
PubMed1996

The VH and CH immunoglobulin genes of swine: implications for repertoire development.

Swine have the largest number of IgG subclass genes of all species so far studied but have a single gene for IgA which occurs in two allelic forms that differ in hinge length. Swine also have constant region genes for C mu and C epsilon, but lack a gene homologous to that which encodes IgD in rodents and primates, despite the otherwise high degree of sequence similarity of all other swine CH genes with those of humans. Swine have < 20 VH genes, a single JH and perhaps a limited number of DH segments. Newborn piglets show preferential VH and DH usage and may use gene conversion as a mechanism for expanding their antibody repertoire. Despite the close similarity of their Ig gene sequences to humans, swine belong to the group of animals that includes rabbits, chickens and cattle when classified on the basis of B cell development. This group, unlike rodents and humans, have a single VH family, use hindgut follicles early in life (rather than bone marrow throughout life) to diversify their antibody repertoire and probably all use gene conversion. It is proposed that IgD may serve a function in repertoire development in rodents and humans which is unnecessary in the chicken-lagomorph-artiodactyl group. The diversity of immunoglobulins and immunoglobulin genes among species justifies the quest of veterinary immunologists to define the system for their species of interest rather than making extrapolations from mouse and human immune systems.

Animals↗
PubMed1996

Molecular characterization of VDJ transcripts from a newborn piglet.

The sequences of 42 transcripts, expressed with IgM, IgG and IgA and cloned from the mesenteric lymph node of a newborn piglet, are described. Forty transcripts used either DHA and DHB and their FR4 were identical to the single swine germline JH. The low frequency of somatic mutation made it possible to identify 35/41 as originating from five putative germline VH genes, of which VHA, VHB and VHC accounted for > 85%. The remaining six transcripts were hybrids of these five germline genes. The most 3' functional VH gene (VH2 = VHB) was the only one exclusively expressed with IgM although VHA, of unknown location in the genome, accounted for half of all transcripts. Junctional diversity in CDR3 was extensive and asymmetrical, in that D-J joining contributed more diversity than V-DJ joining. Reading frame II was used twice as frequently as frame III and the CDR3 generated using the former would have a higher expected R/S ratio. This study indicated that the expressed VH repertoire of the newborn piglet is restricted and nearly germline although junctional diversity is mature and better developed than in fetal mice. The hybrid clones suggest that swine compensate for their < 20 VH genes and single JH by using somatic gene conversion. There was no evidence for exclusive or preferential expression of the most 3' VH gene as occurs in chickens and rabbits respectively, and switching to downstream constant regions probably occurs in utero, even in the theoretical absence of environmental antigens and maternal regulatory molecules. Preferential VHA expression is probably a selection phenomenon.

Amino Acid Sequence↗
PubMed1996

The swine Ig heavy chain locus has a single JH and no identifiable IgD.

Sequence analysis of 84 V region cDNAs expressed with IgM, IgG and IgA from both adult and newborn swine suggested that their JH segments had been derived from the same germline JH. Only a single hybridizing JH segment could be identified in genomic DNA, in a JH-C mu cosmid and in a Sacl fragment of the cosmid extending 5 kb 5' of the EnhH. The single germline JH segment mapped 6 kb 5' to C mu. This JH had a sequence identical to 40 of 42 JH segments expressed in a newborn piglet and 25 of 42 expressed by adult swine. None of the 19 JH segments which varied from the germline sequence were identical to each other and half of the nucleotide changes were silent. No cosmid DNA hybridizing with heterologous probes for C delta could be found within 20 kb 3' of C mu and C delta could not be cloned from genomic or cDNA libraries. A conserved IgD fragment could be amplified from human, mouse and rat genomic DNA but not from rabbit, swine or cattle. We hypothesize that heavy chain organization and constituency in homeothermic vertebrates is correlated with the site of secondary antibody repertoire development and the mechanism(s) used.

Animals↗
PubMed1996

Impaired reflex responses to airway occlusion in the inspiratory muscles of asthmatic subjects.

BACKGROUND: Asthmatic subjects have an impaired capacity to activate the diaphragm during attempted maximal inspiratory efforts. Limb muscles require reflex facilitation to achieve maximal force. The reflex responses of inspiratory muscles to airway occlusion in asthmatic subjects were measured and compared with those in non-asthmatic control subjects. METHODS: Nine healthy asthmatic subjects breathed at a constant inspiratory flow through a low resistance valve. Random inspirations were transiently occluded for 250 ms. Surface electromyographic activity (EMG) was recorded over the scalene muscles, parasternal intercostal muscles, and the lateral chest wall overlying the diaphragm. The asthmatic subjects were studied with and without bronchoconstriction. Responses were compared with data from a matched group of 12 control subjects. RESULTS: Compared with the reflex responses to airway occlusion in control subjects, the duration of the initial short latency inhibition of inspiratory muscles was prolonged by 50% in asthmatic subjects and the size of the subsequent excitation was reduced by 30%. Bronchoconstriction reduced the time to the peak of the excitatory response in asthmatic subjects, although the values remained longer than in the control subjects. CONCLUSIONS: This study reveals impaired reflex excitation of inspiratory motoneurones in asthmatic subjects which could contribute to the reduced ability of these subjects to drive the diaphragm during maximal volitional efforts.

Adolescent↗
PubMed1995

Role of airway receptors in the reflex responses of human inspiratory muscles to airway occlusion.

1. This study was designed to investigate the role of airway receptors in the responses of a range of inspiratory muscles to airway occlusion. The occlusion had a rapid onset (< 10 ms), lasted 250 ms and produced only a slight impediment to inspiration. 2. Based on analysis of single trials and averaged rectified electromyographic responses (EMG) in six subjects, there was a major inhibition (IR) with an onset at 34 +/- 2 ms and a trough at 65 +/- 2 ms, and an excitation (ER) with a peak at 105 +/- 2 ms. These two responses are reflex given that voluntary reaction times to a tap on the chest wall occurred at latencies longer than the peak of ER. 3. The responses to airway occlusion did not appear in limb muscles which contracted phasically with inspiration. 4. Anaesthesia of the surface receptors of the upper airway did not attenuate the responses to occlusion. Because this procedure does not eliminate the inputs from muscle and deep laryngeal pressure receptors, two subjects were tested when intubated with a cuffed endotracheal tube so that the occlusion was delivered only to structures below the level of the trachea. Responses to airway occlusion were preserved when all upper airway receptors were 'bypassed'. 5. Responses to airway occlusion also remained after prolonged inhalation of nebulized lidocaine (lignocaine) sufficient to block the cough reflex. 6. The receptors mediating the responses to airway occlusion are therefore likely to reside in inspiratory muscles acting on the chest wall. If so, the short-latency inhibition contrasts with the excitatory stretch reflex responses observed in limb muscles.

Adaptation, Physiological↗
PubMed1995

The hinge deletion allelic variant of porcine IgA results from a mutation at the splice acceptor site in the first C alpha intron.

Recently published genomic and cDNA sequences for porcine IgA suggested that the splice acceptor site in the C alpha 1-C alpha 2 intron was an AA rather than an AG dinucleotide. This possibility was tested in an in vitro HeLa cell splicing system using an RNA substrate corresponding to the genomic DNA with the putative AA splice site. Data indicated that splicing occurred at a cryptic AG site 12 nucleotides into the C alpha 2 domain rather than at the AA site. The possibility that swine B cells could use either site was tested by preparing the cDNAs from 13 different samples representing nine animals and amplifying the segment from the first C alpha 1 nucleotide to nucleotide 532 in C alpha 2 (genomic DNA numbering system). Analysis on a 6% polyacrylamide sequencing gel revealed two polynucleotide products in most samples that differed by the expected 12 nucleotides, suggesting that swine could use both splice sites. Sequence analysis confirmed that the shorter form was spliced at the downstream site and the larger form at the apparent upstream AA site. However, when the genomic DNA from an animal expressing only the longer polynucleotide was cloned and sequenced, the upstream splice acceptor site was AG not AA. Thus the data suggested that porcine IgA occurred in two allelic forms, designated IgAa and IgAb, which differ by an apparent G to A mutation in the last nucleotide of intron 1 resulting in a short-hinged (two amino acids, IgAb) variant, in which the downstream cryptic splice site is used, as well as a "normal-hinged" (six amino acids, IgAa) variant. Evidence that IgAa and IgAb are allelic was confirmed by genotypic analyses of progeny from matings of IgAa/IgAb heterozygotes. Evidence that both transcripts are functional was confirmed by showing that serum IgA levels were similar in animals homozygous for each variant.

Alleles↗
PubMed1995

The complete cDNA and deduced amino acid sequence of equine IgE.

The cDNA from a transcript encoding the complete heavy chain of the equine immunoglobulin IgE has been cloned and sequenced. A fragment of the equine epsilon gene was amplified from cDNA using PCR and this fragment was then used to probe a horse cDNA library prepared from peripheral blood lymphocytes. A recombinant clone containing the cDNA encoding the complete horse epsilon chain and its associated V-D-J and leader, was subsequently isolated and sequenced. Comparison of the deduced amino acid sequence of equine IgE with the C epsilon heavy chains of other species indicates it to be most similar to human C epsilon (54%), followed by sheep C epsilon (52%); the greatest sequence similarity was found in the C epsilon 3 and C epsilon 4 domains among the species compared. The associated V-region had greatest similarity in FR1 to those reported for sheep and the cow (> 80%) but less than 60% to the VH sequences of other species in FR3.

Amino Acid Sequence↗
PubMed1995

The heterogeneity of bovine IgG2. VII. The phenotypic distribution of the A1 and A2 allotypes of IgG2a among beef cows with known clinical history.

A1 and A2 are allotypes of bovine IgG2a which differ significantly in their primary structure, allotope expression and the products of pepsin digestion. An analysis of 754 beef cows from 14 different breeds at the Meat Animal Research Center (MARC), Clay Center, NE, demonstrated a significant difference in the distribution of A1 and A2 among breeds but failed to find any correlation between the clinical disease history of the animals tested and their A-allotype. The proportion of all animals with either a history of infectious or respiratory disease (43.3 +/- 3.5 and 17 +/- 0, respectively) was the same among A1/A1, A1/A2 and A2/A2 animals. Similarly, there was no preferential association between allotype and clinical disease within any one breed. A very high incidence of A1 homozygotes was found among Angus (84%), Brown Swiss (100%), Limousin (87%), MARC I (87%) and Pinzgauers (88%). In contrast, Herefords had a high incidence of A2/A2 homozygotes (41%) as did Brahmans (46%) and Gelbveih (34%). The distribution of A1/A1, A1/A2 and A2/A2 animals within any breed was totally consistent with the concept that A1 and A2 represent Mendelian co-dominant alleles. These data suggest that, among vaccinated female beef cattle in a normal environment, A-allotypy plays no role in the propensity for clinical disease as defined in this study. It does not rule out such an association in non-vaccinated, severely stressed animals and in calves exposed to severe outbreaks of an infectious agent.

Animals↗
PubMed1994

Expressed swine VH genes belong to a small VH gene family homologous to human VHIII.

The sequences of 34 swine H chain V-regions expressed with either IgG, IgA, or IgM C regions in adult swine and newborn piglets are described and compared. Sixteen of these V-regions were cloned by using a specific leader primer whereas 18 were cloned by anchored PCR. According to the operational criterion of VH family classification, i.e., > 80% DNA sequence similarity, all sequences belong to a homogeneous VH gene family. A total of 31 additional VH-bearing C mu clones obtained by anchored PCR from colostrum-deprived newborn piglets hybridized equally with a probe for C mu and a pan-VH probe. When the consensus sequence of the expressed swine VH genes were compared with those of VH gene for humans (VHI, II, III), mouse (VHI, II, III), rabbit, and chicken, swine VH genes seem to have common ancestry with the human VHIII family, rabbit VH genes, and the single functional VH gene of the chicken. The leader peptides of all clones obtained by anchored PCR showed < 1% variability, and the deduced amino acid sequences from aa4 to aa25 in all 34 clones are identical. Framework (FR)1 and FR2 are conserved whereas FR3 shows greater variability. A total of 23 of 30 JH sequences were identical, suggesting preferential use of one JH. This frequent, putative JH sequence is not similar to any JH gene in humans. Identical genomic Southern hybridization patterns, each with 13 bands of differing intensity and regardless of stringency, were obtained when either a leader or a pan-specific VH probe was used. Analyses of individual genomic bands by single strand conformational polymorphism and sequence analysis suggest that the number of VHIII-related genes in the swine genome is < 20.

Amino Acid Sequence↗
PubMed1994

Five putative subclasses of swine IgG identified from the cDNA sequences of a single animal.

We report the sequences of more than 40 partial and complete swine C gamma cDNAs obtained by PCR cloning of first strand cDNA, and from a cDNA expression library, all from a single animal. These seem to represent five IgG subclasses, that can be grouped into two clusters; one contains IgG1 and IgG3 and the other, IgG2a, IgG2b and IgG4. IgG2a and IgG2b differ by only three amino acids, but single strand conformational polymorphism analyses of PCR-amplified IgG2-specific segments in animals of different breeds, argues for their putative subclass status. Major subclass differences are found in the hinge and C gamma 3, but differences in upper hinge length, associated with segmental flexibility in the IgGs of other species, are absent. All subclasses have identical middle hinge segments that can accommodate three interheavy chain disulfide bridges. The putative swine IgG subclasses have their greatest similarity with those of the human except for the near absence of hinge region variation. Swine subclasses such as ruminant IgG2a, have a lower hinge deletion which in human IgG1, contains one of the motifs believed necessary for interaction with Fc gamma Rs. IgG1 was the most frequently encountered subclass cDNA (25 of 43) and the single swine-mouse hybridoma tested had a sequence identical to IgG1. Partial sequence analyses of genomic clones identified one clone identical with the IgG1/IgG3 subclass cluster, two identical to the IgG2b/IgG4 subclass group, and two identical to each other but different from any of the expressed sequences reported here. Genomic blots suggest that up to eight C gamma genes are present in the genome.

Animals↗