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Biomedical subjects

J L Morrison

Publications and source records attributed to J L Morrison.

At least 19 recordsLinked to original sources
PubMed2006

Contractile and Ca2+-handling properties of the right ventricular papillary muscle in the late-gestation sheep fetus.

The force-generating capacity of cardiomyocytes rapidly changes during gestation and early postnatal life coinciding with a transition in cardiomyocyte nucleation in both mice and rats. Changes in nucleation, in turn, appear to coincide with important changes in the excitation-contraction coupling architecture. However, it is not clear whether similar changes are observed in other mammals in which this transition occurs prenatally, such as sheep. Using small (70-300 microM diameter) chemically skinned cardiomyocyte bundles from the right ventricular papillary muscle of sheep fetuses at 126-132 and 137-140 days (d) gestational age (GA), we aimed to examine whether changes in cardiomyocyte nucleation during late gestation coincided with developmental changes in excitation-contraction coupling parameters (e.g., Ca(2+) uptake, Ca(2+) release, and force development). All experiments were conducted at room temperature (23 +/- 1 degrees C). We found that the proportion of mononucleate cardiomyocytes decreased significantly with GA (126-132 d, 45.7 +/- 4.7%, n = 7; 137-140 d, 32.8 +/- 1.6%, n = 6; P < 0.05). When we then examined force development between the two groups, there was no significant difference in either the maximal Ca(2+)-activated force (6.73 +/- 1.54 mN/mm(2), n = 14 vs. 6.55 +/- 1.25 mN/mm(2), n = 7, respectively) or the Ca(2+) sensitivity of the contractile apparatus (pCa at 50% maximum Ca(2+)-activated force: 126-132 d, 6.17 +/- 0.06, n = 14; 137-140 d, 6.24 +/- 0.08, n = 7). However, sarcoplasmic reticulum (SR) Ca(2+) uptake rates (but not Ca(2+) release) increased with GA (P < 0.05). These data reveal that during late gestation in sheep when there is a major transition in cardiomyocyte nucleation, SR Ca(2+) uptake rates increase, which would influence total SR Ca(2+) content and force production.

Animals↗
PubMed2004

Differential regulation of behavioral, genomic, and neuroendocrine responses by CRF infusions in rats.

Studies suggest that behavioral, genomic, and endocrine functions mediated by central corticotropin-releasing factor (CRF)-containing circuits may be differentially regulated. However, this hypothesis has never been tested directly by simultaneous assessment of distinct CRF-mediated responses within the same animal. The present study addressed this issue by concurrently examining the effects of central CRF infusions on anxiety responses, plasma corticosterone release, and c-fos mRNA induction within limbic brain circuits. Bilateral intracerebroventricular (icv) infusions of CRF (0.1-10 microg total) dose-dependently reduced exploratory behavior in a novel open field, increased circulating corticosterone (CORT) levels and augmented c-fos mRNA expression in the central nucleus of the amygdala (CeA) and the hypothalamic paraventricular nucleus (PVN). Plasma CORT levels increased significantly after 0.1 microg CRF, whereas behavioral and genomic responses required at least 1 microg CRF, suggesting that the distinct responses mediated by CRF are differentially regulated. Further characterization of intracerebroventricular CRF at 1 microg also demonstrated a disruption of social interaction behavior. The majority of behavioral effects and the elevated c-fos mRNA expression were attenuated by 10 mg/kg DMP696, a CRF(1) antagonist. However, plasma CORT elevation required 30 mg/kg DMP696 for attenuation. Thus, our studies demonstrate a greater sensitivity of the hypothalamic-pituitary-adrenal axis to intracerebroventricular CRF compared with the induction of innate fear-like responses and associated genomic changes.

Adrenocorticotropic Hormone↗
PubMed2003

Suppression of genioglossus muscle tone and activity during reflex hypercapnic stimulation by GABA(A) mechanisms at the hypoglossal motor nucleus in vivo.

The genioglossus muscle is involved in the maintenance of an open airway for effective breathing. Inhibitory neurotransmitters may be responsible for the major suppression of hypoglossal motor output to genioglossus muscle that occurs in certain behaviours such as rapid-eye-movement sleep. There is evidence for GABA(A) receptor-mediated inhibition of hypoglossal motoneurons in vitro. However, comparable studies have not been performed in vivo and the interactions of such mechanisms with integrative reflex respiratory control have also not been determined. Urethane-anaesthetised, tracheotomized and vagotomized rats were studied whilst diaphragm and genioglossus muscle activities, blood pressure and the electroencephalogram were recorded. Microdialysis probes were implanted into the hypoglossal motor nucleus, with sites verified by histology. Genioglossus responses to microdialysis perfusion of muscimol (GABA(A) agonist: 0, 0.1, 1 and 10 microM in artificial cerebrospinal fluid) were recorded at inspired CO(2)s of 0, 5 and 7.5% in six rats. Responses to bicuculline (GABA(A) antagonist, 0, 1, 10, 100 and 1000 microM) were also studied in six rats with and without CO(2) stimulation. Genioglossus activity decreased with muscimol (P<0.0001), with major suppression at 1 and 10 microM during air breathing (decreases=70.2% and 92.8%, P<0.005). Genioglossus activity increased with CO(2) (P=0.003), but genioglossus activation with 5 and 7.5% CO(2) were almost abolished with 10-microM muscimol. Responses were specific to genioglossus muscle as there were no changes in diaphragm, respiratory rate or blood pressure with muscimol (P>0.144). Antagonism of GABA(A) receptors increased genioglossus activity (P<0.001). These results show that GABA(A) receptor stimulation at the hypoglossal motor nucleus suppresses both genioglossus muscle tone and activity in the presence of reflex stimulation produced by hypercapnia. Recruitment of such mechanisms may contribute to the major suppression of genioglossus activity observed with and without CO(2) stimulation in behaviours such as rapid-eye-movement sleep.

Animals↗
PubMed2003

Eosinophilic "empyema" associated with crack cocaine use.

Smoking of crystalline cocaine, known as "crack" cocaine, has been associated with eosinophilic pneumonitis, but not with pleural effusions. We describe a patient with eosinophilic pneumonitis with an eosinophilic "empyema" after using "crack" cocaine. The illness resolved with corticosteroids. We hypothesised that his effusion would have increased levels of eosinophil cytokines that promote oedema, and found a marked increase in pleural vascular endothelial growth factor (VEGF) and smaller increases in interleukins IL-5, IL-6, and IL-8. In the setting of "crack" use, we suggest that a pleural effusion that appears grossly to be pus should be evaluated for eosinophilic inflammation. Such eosinophilic effusions may respond to corticosteroids alone, consistent with a non-infectious process driven by proinflammatory cytokines.

Administration, Oral↗
PubMed2001

Fetal behavioural state changes following maternal fluoxetine infusion in sheep.

Clinical depression is diagnosed in 5-15% of women during pregnancy, increasing the risk of negative outcomes. Fluoxetine (FX), a selective serotonin reuptake inhibitor, is prescribed during pregnancy. In adults, FX alters sleep patterns with single doses decreasing total sleep time and rapid eye movement sleep. The effects of FX on sleep in the fetus are unknown. However, 5-hydroxytryptophan, the precursor of serotonin, has been reported to prolong high-voltage (HV) electrocortical (ECoG) activity and increase the incidence of fetal breathing movements (FBM) in the sheep fetus. We hypothesize that FX exposure will decrease the incidence of LV ECoG in the fetus. Twenty-one pregnant sheep were surgically prepared for chronic study of blood gases, ECoG activity, eye movements and FBM. After 3 days of recovery, ewes received a 70-mg bolus i.v. infusion of FX or sterile water followed by continuous infusion at a rate of 0.036 mg/min for 8 days. The incidence of low-voltage (LV) ECoG decreased from 54+/-4% on the preinfusion day to 45+/-5% on infusion day 1 in the FX group and remained decreased throughout the infusion period. In addition, the incidence of both eye movements and FBM was decreased on infusion day 1 compared to preinfusion day in the FX group. HV ECoG increased from 39+/-3% on preinfusion day to 68+/-14% on FX infusion day 1 and remained elevated throughout the infusion period. These data show that maternal FX administration alters fetal behavioural state.

Animals↗
PubMed2001

A national survey of stress reactions after the September 11, 2001, terrorist attacks.

BACKGROUND: People who are not present at a traumatic event may also experience stress reactions. We assessed the immediate mental health effects of the terrorist attacks on September 11, 2001. METHODS: Using random-digit dialing three to five days after September 11, we interviewed a nationally representative sample of 569 U.S. adults about their reactions to the terrorist attacks and their perceptions of their children's reactions. RESULTS: Forty-four percent of the adults reported one or more substantial stress symptoms; 91 percent had one or more symptoms to at least some degree. Respondents throughout the country reported stress syndromes. They coped by talking with others (98 percent), turning to religion (90 percent), participating in group activities (60 percent), and making donations (36 percent). Eighty-five percent of parents reported that they or other adults in the household had talked to their children about the attacks for an hour or more; 34 percent restricted their children's television viewing. Thirty-five percent of children had one or more stress symptoms, and 47 percent were worried about their own safety or the safety of loved ones. CONCLUSIONS: After the September 11 terrorist attacks, Americans across the country, including children, had substantial symptoms of stress. Even clinicians who practice in regions that are far from the recent attacks should be prepared to assist people with trauma-related symptoms of stress.

Adaptation, Psychological↗
PubMed2001

Bayes estimates of haplotype effects.

We describe a Markov chain Monte Carlo implementation of a Bayesian approach to estimating associations of a trait with a large set of haplotypes recently introduced by Clayton and Jones [Am J Hum Genet 65:1161-9, 2000]. The model uses the length of the longest segment in common between any two haplotypes to define the prior correlation structure for the set of haplotype effects, using an intrinsic autocorrelation model. When applied to the Genetic Analysis Workshop 12 data for trait Q1, we found highly significant variation between haplotypes, using either a structured or unstructured covariance matrix.

Bayes Theorem↗
PubMed2001

Should we consider gene x environment interaction in the hunt for quantitative trait loci?

We address the question of whether one can obtain increased power for finding a quantitative trait locus (QTL) if a gene x environment (G x E) interaction is incorporated directly into the linkage analysis. We consider both parametric and nonparametric analysis approaches to including G x E interaction. For the former, we utilize joint segregation and linkage analysis to estimate simultaneously the recombination fraction and a G x E interaction effect, as well as the remaining model parameters. The nonparametric approach is based on an extension of the Haseman-Elston method applied to sib pairs to include a regression of the squared trait difference on marker-identity-by-descent (IBD) probability (pi), the sibling covariate sum (z), and pi x z. We utilize 50 replicates of the simulated data and compare empirical power of the various approaches to detect MG4, a locus that is involved in a strong interaction with age for Q4 and in a weaker interaction with environmental factor E2 for Q3. Using the parametric approach, including a G x age effect does increase power for detecting linkage between MG4 and Q4 compared with ignoring the interaction (powers 58% and 38%, respectively, to exceed a lod score of 3.0). On the other hand, including a G x E2 interaction has little effect on the power to detect linkage between MG4 and Q3. The nonparametric approach leads to qualitatively similar findings. We conclude that it is beneficial to incorporate G x E interaction into a linkage analysis, provided the interaction effect is of sufficiently strong magnitude.

Chromosome Mapping↗
PubMed2001

Leucocytozoon toddi and Haemoproteus tinnunculi (Protozoa: Haemosporina) in the Chimango caracara (Milvago chimango) in southern Chile.

Two species of blood protozoans were identified from blood smears collected from 15 specimens of the Chimango caracara (Milvago chimango) on Isla Grande de Chiloé in southern Chile. These included Leucocytozoon toddi in 13 birds, including all 5 of the 4-6 week old nestlings examined, and 8 of the subadults or adults. One of the nestlings also had a dual infection of L. toddi and Haemoproteus tinnunculi. These are the first reports of blood parasites from M. chimango.

Animals↗
PubMed2000

Evidence for age-specific genetic relative risks in lung cancer.

Recent studies of familial aggregation suggest that family history of lung cancer among first-degree relatives is associated with increased risk for early-onset, but not late-onset, lung cancer. To assess whether this could be explained by variability in genetic relative risk across age, segregation analysis was performed on the Louisiana Lung Cancer Dataset. This data set consisted of 337 probands who died of lung cancer between 1976 and 1979 and their first-degree relatives. A variation of the Cox proportional hazards model was used that allowed estimation of age- and genotype-specific incidence rates, from which the authors obtained estimates of age-specific genetic relative risks. The best-fitting model included an autosomal dominant locus (allele frequency, 0.043), with carrier-to-noncarrier relative risks that exceeded 100 for ages less than 60 years and declined monotonically to 1.6 by age 80. The hypothesis of proportional genetic relative risk across age was rejected (p = 0.009). The estimated proportion of persons with lung cancer who carry the high-risk allele exceeds 90% for cases with onset at age 60 years or less and decreases to approximately 10% for cases with onset at age 80 years or older. These findings support previous evidence of a major susceptibility locus for lung cancer and suggest that linkage studies should preferentially recruit young lung cancer cases and their relatives.

Adolescent↗
PubMed2000

Pedicle marrow signal intensity changes in the lumbar spine: a manifestation of facet degenerative joint disease.

OBJECTIVE: Signal intensity changes in lumbar pedicles, similar to those described in vertebral body endplates adjacent to degenerated discs, have been described as an ancillary sign of spondylolysis on MRI. The purpose of this study was to determine whether pedicle marrow signal intensity changes also occur in association with facet degenerative joint disease. DESIGN: Eighty-nine lumbar spine MRI examinations without spondylolysis were reviewed for marrow signal intensity changes in pedicles and vertebral bodies as well as for facet degenerative joint disease. RESULTS: Five percent (46/890) of lumbar pedicles in 23 patients had marrow signal intensity changes. Ninety-one percent (42/46) of the abnormal pedicles had adjacent degenerative joint disease of the facets, while only 21% (189/890) of normal pedicles had adjacent facet degenerative joint disease (p<0.001). Eighty-nine percent (41/46) of the pedicles with marrow signal intensity changes had adjacent degenerative disc disease. CONCLUSIONS: Pedicle marrow signal intensity changes are not a specific sign of spondylolysis; they are commonly seen with adjacent facet degenerative joint disease in the absence of spondylolysis. Pedicle marrow signal intensity changes are probably a response to abnormal stresses related to abnormal motion or loading caused by the degenerative changes in the spinal segment.

Adult↗
PubMed2000

Herpesviruses and periodontopathic bacteria in Trisomy 21 periodontitis.

BACKGROUND: Little is known about the etiology and pathogenesis of periodontal disease in Trisomy 21 patients. This study determined the occurrence of herpesviruses and putative periodontopathic bacteria in Trisomy 21 periodontitis. METHODS: Nineteen Trisomy 21 patients (17 to 37 years of age) contributed subgingival samples from molar and bicuspid teeth presenting interproximal periodontitis lesions (probing depths, 5 to 8 mm) and from shallow periodontal sites (probing depths, 1 to 3 mm). Samples were obtained at baseline, and at 1 and 4 weeks after subgingival debridement by means of hand instruments and ultrasonic scalers. Epstein-Barr virus type 1 and 2 (EBV-1 and EBV-2), human cytomegalovirus (HCMV), and herpes simplex virus (HSV) were identified by sensitive and specific nested polymerase chain reaction. Putative periodontopathic bacteria were identified by means of non-selective and selective culture. RESULTS: Of 19 Trisomy 21 periodontitis lesions, 6 (32%) were positive for EBV-1, 5 (26%) were positive for HCMV, 3 (16%) were positive for HSV, and 2 (11%) showed viral co-infection. Of 19 shallow periodontal sites, only one revealed HCMV. Prevotella intermedia, Bacteroides forsythus, and Capnocytophaga species were detected in higher proportions in deep than in shallow periodontal pockets (P = 0.02). Subgingival debridement did not reduce genomic herpesvirus presence but caused a decrease in proportions of Porphyromonas gingivalis and Capnocytophaga species. CONCLUSIONS: Periodontal herpesvirus-bacteria coinfections may play important roles in the pathogenesis of destructive periodontal disease in Trisomy 21 patients. Herpesviruses may reduce the periodontal defense and promote growth of subgingival bacteria capable of causing periodontal breakdown.

Adolescent↗
PubMed2000

Water on the knee: cysts, bursae, and recesses.

Many synovial-lined cavities occur around the knee, and MR imaging is capable of demonstrating the precise anatomic relationships of these spaces. Knowledge of normal anatomy, however, is necessary to accurately assess abnormal, fluid-filled structures. This article reviews the MR imaging appearance of normal and pathologic bursae and joint recesses, and the appearance of common cystic masses. Distinguishing features of several noncystic lesions occurring around the knee also are discussed because these can mimic bursae, recesses, and cysts.

Body Water↗
PubMed1999

A generalized estimating equations approach to linkage analysis in sibships in relation to multiple markers and exposure factors.

We describe a multiple regression approach to nonparametric linkage analysis in sibships incorporating multiple genetic loci, environmental covariates, and interactions. The covariance in trait residuals between sib pairs is treated as the dependent variable, regressed upon identical-by-descent sharing probabilities and interaction effects, using generalized estimating equations to allow for the correlations among multiple sib pairs within a sibship. Individual covariates can also be introduced in the model for the trait means. An application to the GAW11 simulated data revealed linkage with each of the four simulated loci, as well as gene x environment interactions of E1 with loci C and D and gene x gene interactions among the cluster of loci A, B, and D.

Environment↗
PubMed1999

A joint test of linkage and gene x environment interaction, with affected sib pairs.

In the presence of gene x environment (G x E) interaction, the expected proportion of alleles shared identical by descent at a linked marker locus by a pair of affected sibs depends on the exposure profile of the two sibs, i.e., whether both are exposed to E, only one is exposed, or neither are exposed. In this paper, we propose an extension of the commonly used mean test of linkage to test for differential identical-by-descent (IBD) sharing across sib-exposure profiles. The method can be viewed as a test for linkage in the presence of G x E interaction, or as a test for G x E interaction in the presence of linkage. Applied to the simulated GAW11 data, our method successfully localized disease locus C and its interactive relationship with environmental factor E1. At the 5% significance level, use of our method led to increased power to detect linkage (56%) to this disease locus compared to use of the standard mean test (32%); at the 0.001 significance level, the corresponding power estimates were 20% and 4%, respectively. For a gene that interacts with an environmental factor, we conclude that use of the environmental factor in linkage analysis can improve detection rates while also providing information about underlying mechanisms.

Alleles↗
PubMed1999

Relationship between herpesviruses and adult periodontitis and periodontopathic bacteria.

BACKGROUND: Various mammalian viruses and specific bacteria seem to play important roles in the pathogenesis of human periodontitis. This study examined the relationship between subgingival herpesviruses and periodontal disease and potential periodontopathic bacteria in 140 adults exhibiting either periodontitis or gingivitis. METHODS: A nested-polymerase chain reaction (PCR) method determined the presence of Epstein-Barr virus type 1 and type 2 (EBV-1, EBV-2), human cytomegalovirus (HCMV), and herpes simplex virus (HSV) and a 16S rRNA PCR detection method identified Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forsythus, Prevotella intermedia, Prevotella nigrescens, and Treponema denticola. RESULTS: Using a logistic analysis, EBV-1 showed significant positive association with P. gingivalis (odds ratio [OR] 3.37), and with coinfections of P. gingivalis and P. intermedia (OR 4.03); P. gingivalis and B. forsythus (OR 3.84); P. gingivalis and T. denticola (OR 4.17); P. gingivalis, B. forsythus, and T. denticola (OR 4.06); and P. gingivalis, P. nigrescens, and T. denticola (OR 3.29). EBV-1 also showed positive association with severe periodontitis (OR 5.09), with increasing age (OR 1.03), and with periodontal probing depth at the sample sites (OR 1.77). HCMV was positively associated with coinfections of P. gingivalis and P. nigrescens (OR 3.23); P. gingivalis, B. forsythus, and P. nigrescens (OR 3.23); and P. gingivalis, P. nigrescens, and T. denticola (OR 2.59); with severe periodontitis (OR 4.65); and with age (OR 1.03). Patients with mixed viral infections revealed significant associations with P. gingivalis (OR 2.27), and with coinfections of P. gingivalis and B. forsythus (OR 2.06); P. gingivalis and P. nigrescens (OR 2.91); P. gingivalis, B. forsythus, and P. nigrescens (OR 2.91); and P. gingivalis, P. nigrescens, and T. denticola (OR 2.70) with the clinical diagnosis of slight (OR 3.73), moderate (OR 3.82), or severe periodontitis (OR 4.36), and with probing depth at the sample sites (OR 1.39). HSV and EBV-2 showed no significant associations with any of the variables tested. CONCLUSIONS: The results indicate that subgingival EBV-1, HCMV, and viral coinfections are associated with the subgingival presence of some periodontal pathogens and periodontitis. Herpesviruses may exert periodontopathic potential by decreasing the host resistance against subgingival colonization and multiplication of periodontal pathogens.

Actinobacillus Infections↗
PubMed1999

Tetracycline-coated polytetrafluoroethylene barrier membranes in the treatment of intraosseous periodontal lesions.

BACKGROUND: Periodontal pathogens are detrimental to periodontal healing in barrier membrane-assisted periodontal therapy. Tetracycline-coating of barrier membranes may reduce levels of infecting pathogens. This study evaluated the clinical and microbiological effects of tetracycline-coated expanded polytetrafluoroethylene (T-ePTFE) barrier membranes in the treatment of 2- to 3-wall intraosseous periodontal lesions around mandibular molars. METHODS: Eleven patients received non-coated barrier membranes (ePTFE) and 11 patients received T-ePTFE barrier membranes. Tetracycline coating was performed by placing ePTFE membranes first in a 5% tridodecylmethylammonium chloride solution and then in a basic 3% tetracycline solution. Microbiological examination included conventional culture and DNA probe analyses. Barrier membranes were removed 6 weeks after insertion. RESULTS: At baseline, the periodontal lesion depth averaged 8.0 mm in the ePTFE treated group and 7.4 mm in the T-ePTFE group. At 1 year post-treatment, the mean gain of probing attachment was 1.9 mm in the ePTFE group and 3.3 mm in the T-ePTFE group (P = 0.02). At 3 minutes after membrane placement, suspected periodontal pathogens were detected in several ePTFE membranes but only in one T-ePTFE membrane. At 6 weeks, all membranes showed periodontal pathogens, including Porphyromonas gingivalis, Fusobacterium species, Peptostreptococcus micros, Bacteroides forsythus, and motile rods. CONCLUSIONS: This study suggests that the use of tetracycline-coated ePTFE barrier membranes can result in additional gain of clinical periodontal attachment, most likely due to the antimicrobial properties of tetracycline during initial healing.

Adult↗