Biomedical subjects

D R Grimm

Publications and source records attributed to D R Grimm.

30 records · Page 2Linked to original sources

PubMed1998

The effects of ipratropium bromide on histamine-induced bronchoconstriction in subjects with cervical spinal cord injury.

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.

Adult↗

PubMed1997

Molecular cloning of cDNA encoding porcine interleukin-15.

Interleukin-15 (IL-15) is a recently identified growth and differentiation factor with an important potential role in the initial immune responses to infection. To enable the study of the role of this cytokine in the protective immune-mechanisms generated against parasitic diseases of swine, cDNA was generated from a macrophage enriched adherent cell population from peripheral blood mononuclear cells (PBMC). This cDNA was used for the enzymatic amplification of the porcine IL-15 sequence using human IL-15-derived primers. The open-reading frame of the porcine IL-15 cDNA is 486 base pairs (bp) in length and encodes a 162-amino-acid (aa) protein. Comparisons of the predicted swine protein sequence with those predicted from human, bovine and mouse IL-15 sequences indicate similarities of 82.1, 84.6, and 71.6%, respectively.

Amino Acid Sequence↗

PubMed1997

Effects of GABA-B agonist baclofen on bronchial hyperreactivity to inhaled histamine in subjects with cervical spinal cord injury.

Bronchial provocation studies performed in our research center have consistently demonstrated airway hyperresponsiveness to both inhaled methacholine and histamine in subjects with chronic cervical spinal cord injury (SCI). More recently, we reported that the airways of such subjects maintained on chronic baclofen (gamma-aminobutyric acid) therapy were not hyperreactive to inhaled methacholine. In this study we determined whether baclofen also blocks the effects of the bronchoprovocative agent histamine in subjects with cervical SCI. Twenty-four male subjects with cervical SCI participated in this study; 14 were maintained on oral baclofen, and 10 served as age-matched controls. The subjects were challenged with increasing concentrations of aerosolized histamine until either a 20% fall in forced expiratory volume in 1 s (FEV1) from baseline (defined as PC20) was observed, or a maximum of 25 mg/ml histamine was administered. We found that 11 of the 14 baclofen subjects (78.5%) and 8 of the 10 control subjects (80%) responded (PC20 < 8 mg/ml) to the histamine challenge. Mean PC20 values among responders in the baclofen (PC20 = 2.91 +/- 2.3) and control (PC20 = 2.18 +/- 1.9) groups did not differ significantly. Because histamine acts directly on histamine receptors and indirectly on cholinergic pathways, our findings that baclofen blocks bronchoconstriction due to inhaled methacholine, but not that due to histamine, suggests that hyperresponsiveness in subjects with cervical SCI may be secondary to nonspecific airway hyperreactivity.

Adult↗

PubMed1997

Mapping of microsatellite markers developed from a flow-sorted swine chromosome 6 library.

Swine Chromosome (Chr) 6-enriched libraries, generated with size-fractionated DNA isolated from chromosomes sorted by flow cytometry, have been used to develop new Chr 6 microsatellite markers. Chromosome isolation procedures were established to reproducibly prepare high quality chromosomes from phytohemagglutinin (PHA)-stimulated swine peripheral blood lymphocytes and to sort individual chromosomes after staining with Hoechst 33258 and chromomycin A3. Chromosome purity was verified by specific staining of swine Chr 6 with fluorescence in situ hybridization (FISH) by use of painting probes generated by degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) amplification of as few as 300 sorted Chr 6. For library construction, DNA was extracted from flow-sorted pools representing Chr 6, amplified, size selected for fragments from 300 to 700 bp, and ligated into pBluescript SK II+ or Lambda ZAP Express. The libraries were then screened with a radiolabeled poly-(dCA) DNA probe. Of 107 (CA)n repeat-containing clones verified by sequencing, 21 were polymorphic and used to genotype the University of Illinois swine reference families. Linkage analysis was then performed with CRIMAP 2.4 (LOD > 3.0), and the results showed that 15 of the microsatellites mapped to swine Chr 6. At least three of these new markers map to locations where there were gaps in the consensus Chr 6 map. Another four markers, because of their PIC values, should provide more informative markers in other areas of the map. Most of the new markers can also be used for automated genotyping with fluorescent labeling. This set of 15 new Chr 6 markers will, therefore, be useful in helping to define QTL associated with swine Chr 6.

Animals↗

PubMed1997

Self-reported prevalence of pulmonary symptoms in subjects with spinal cord injury.

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.

Adult↗

PubMed1997

Neurally mediated syncope: a review of cardiac and arterial receptors.

This article reviews the basic physiology of the reflexogenic areas of the heart and the mechano- and baroreceptors that regulate cardiovascular and autonomic homeostasis, all of which contribute to our understanding of the pathogenesis of neurally mediated syncope. The mechanisms of neurally mediated syncope may involve excessive activation of ventricular receptors that trigger severe hypotension and bradycardia. Thus, neurally mediated syncope may be the clinical expression of the Bezold-Jarisch reflex, which occurs in situations of increased sympathetic activity, perhaps as a result of heightened cardiac receptor sensitivity. The arterial baroreceptors exert a ubiquitous influence on the heart and circulation, and serve primarily to buffer transient changes in arterial pressure by transmitting sensory information regarding their stretch to the central nervous system. This information, in conjunction with cardiac receptor input, elicits alterations in neural efferent output from sympathetic and parasympathetic fibers to provide subtle, continuous regulation of beat-to-beat cardiovascular hemodynamics to an array of physiologic and psychological stressors.

Autonomic Nervous System↗

PubMed1997

Sympathovagal balance of the heart in subjects with spinal cord injury.

This study investigated the effect of abnormal autonomic cardiovascular function on heart rate variability (HRV) in individuals classified into four groups: complete quadriplegia, incomplete quadriplegia, low paraplegia, and non-spinal cord injury (SCI) controls. Measurements were collected at baseline and during provocative maneuvers. Spectral analysis using a fast-Fourier transform algorithm revealed two spectral components of HRV, termed low frequency (LF) and high frequency (HF); the LF-to-HF ratio (estimate of sympathovagal balance) was also calculated. Each group of subjects with quadriplegia exhibited significantly lower spectral components for both baseline and composite provocative measures compared with the non-SCI controls (P < 0.05). In addition, the group with paraplegia demonstrated significantly lower HF baseline and LF composite levels than controls (P < 0.05). No differences were observed among all groups for the LF-to-HF ratio. This consistency in the LF-to-HF ratio suggests that the two autonomic divisions that regulate the cardiovascular system maintain homeostasis even when one component is severely compromised. This is supported by the additional findings of decreased parasympathetic activity in the two groups with quadriplegia and the absence of significant differences among any of the four groups at rest in either heart rate or blood pressure.

Adult↗

PubMed1997

Development and use of a microdissected swine chromosome 6 DNA library.

To facilitate the identification of microsatellite genetic markers from a single swine chromosome, chromosome microisolation and microcloning have been used to generate a swine chromosome 6-specific DNA library. Ten copies of swine chromosome 6 were scraped from metaphase spreads, ligated to custom-prepared adaptors, and amplified by PCR. The purity of the amplified product was verified by fluorescent in situ hybridization. The utility of the chromosome painting probe for heterologous painting was demonstrated and confirmed that swine chromosome 6 is syntenic to human chromosomes 1p and 19q. A small insert genomic library of 1.39 x 10(6) clones was generated from the PCR-amplified chromosome 6 genomic DNA and screened for (GT)n microsatellite genetic markers. Nine (GT)n microsatellite markers were developed and genotyped on a Yorkshire x Meishan swine reference family. All nine markers genetically mapped to chromosome 6, confirming the purity of the microisolation method. The method used here should be adaptable to the microdissection of subchromosomal regions of not only the swine genome but also other livestock genomes.

Animals↗

PubMed1995

Effect of provocative maneuvers on heart rate variability in subjects with quadriplegia.

This study investigated heart rate variability (HRV) in individuals with quadriplegia who have disruption of autonomic control of the heart. Seven male subjects with neurological complete quadriplegia and seven with incomplete quadriplegia were studied at rest and during provocation. HRV was measured by power spectral analysis using a fast Fourier transform. Two spectral components were generated: 1) the high-frequency (HF) peak, a reflection of parasympathetic activity, and 2) the low-frequency (LF) peak, primarily sympathetic activity with some parasympathetic input. Results of the provocative maneuvers were grouped into one composite variable. Significant differences in the LF spectral component were found between the groups with complete and incomplete lesions in the supine position and after provocation (LF supine: P = 0.01; LF provocation: P = 0.002). After provocation, significant differences were demonstrated in the HF spectral component between these groups (P = 0.005). In contrast to previous findings, a LF component in subjects with complete quadriplegia was observed; this LF component decreased after provocation, suggesting the parasympathetic component withdrew during stressful maneuvers. There also appeared to be general downregulation of parasympathetic activity to the heart in subjects with complete quadriplegia. The presence of an increased LF spectral component during provocation in those with incomplete lesions implies sympathetic stimulation of the heart and may be used as a marker of sympathetic activity in individuals with quadriplegia.

Cold Temperature↗

PubMed1994

Partial cloning and sequencing of the gene encoding the porcine T-cell receptor delta-chain constant region.

The polymerase chain reaction (PCR) was utilized to clone the pig T-cell receptor (TCR) delta-chain constant region-encoding gene (C delta). A cDNA was generated from total RNA preparations of normal pig peripheral blood lymphocytes (PBLs) and a miniature pig peripheral blood cell line (PBLCL 62.G4). The cDNA was used to amplify the porcine TCR C delta gene by PCR using primers chosen by comparing other known C delta sequences for sequence identity. Clones were sequenced and used to determine the primary structure of the porcine TCR C delta chain. A comparison of the nucleotide and deduced amino acid (aa) sequences with the known human, mouse, sheep and cattle sequences revealed that the primary structure of the pig TCR C delta chain has been highly conserved. The immunoglobulin (Ig) domain has two conserved Cys residues and contains a high degree of sequence identity, whereas the hinge region is marked by a high level of diversity. The transmembrane and cytoplasmic regions are also highly conserved, including the presence of the two basic aa, Arg and Lys, in the transmembrane domain. Southern blot analysis has confirmed the presence of one TCR C delta gene in the porcine genome, consistent with similar findings in other species. Thus, the successful cloning and sequencing of the porcine TCR C delta gene should facilitate our understanding of the role of gamma delta T-lymphocytes in the swine immune system.

Amino Acid Sequence↗

PubMed1994

Sinclair miniature swine: an animal model of human melanoma.

Sinclair swine display cutaneous melanoma lesions and develop a generalized depigmentation subsequent to tumor regression. Sinclair swine represent a valuable animal model to study the factors influencing the development of melanoma and also the factors which lead to the development of vitiligo. Therefore, information obtained in studies of Sinclair swine should facilitate our understanding of the mechanisms by which melanoma and vitiligo develop and provide us with possible therapeutic treatments for these human diseases.

Animals↗

PubMed1993

Isolation and characterization of gamma delta T lymphocyte cell lines from Sinclair swine peripheral blood.

Sinclair miniature swine represent a breed of miniature swine which display a significant incidence of inheritable melanoma which undergo a developmentally regulated spontaneous regression. In an attempt to characterize the host cellular immune response to the melanoma, lymphocyte cell lines have been generated from peripheral blood and designated as peripheral blood lymphocyte cell lines (PBLCLs). The cell lines were expanded in vitro without the addition of exogenous mediators, cloned by limiting dilution, and characterized by flow microfluorimetry, Western, and Northern blot analysis. The cell lines were shown to be CD2-, CD4-, CD8-, and slg-, a phenotype consistent with a null cell population described in swine. The null cell population in swine has been reported to consist of a subpopulation of cells which express the gamma delta T cell receptor (TCR) heterodimer, swine gamma delta T lymphocytes. The PBLCLs were further analyzed by flow microfluorimetry and observed to express the IL-2R, swine MHC Class II antigens, and the endothelial lymphocyte adhesion marker (CD44), which can function as a homing receptor for the skin. In addition, the PBLCLs were observed to express the antigen which is recognized by mAb 86D, an antibody that has been reported to recognize an external epitope on a subset of gamma delta TCR bearing swine T lymphocytes. Western blot analysis of Triton X-114 phase fractions of a PBLCL revealed a protein recognized by the W6 antibody, an antibody which recognizes a conserved region of the C delta chain. Furthermore, Southern and Northern blot analysis indicated that the PBLCL have rearranged the TCR gamma chain gene and express mRNA from the TCR gamma and delta chain genes prior to and following treatment with ionomycin or Concanavalin A. Therefore, the data indicates that the PBLCLs represent swine gamma delta T lymphocyte cell lines which should enable us to enhance our understanding of the role of gamma delta T lymphocytes in the porcine immune system.

Animals↗