Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously developed a method of partitioning genetic variance of a quantitative trait to loci in specific chromosomal regions. In this paper, we compare this method--multipoint IBD (identical by descent) method (MIM)--with parametric multipoint linkage analysis (MLINK). A simulation study was performed comparing the methods for the major-locus, mixed, and two-locus models. The criterion for comparisons between MIM and MLINK was the average lod score from multiple replicates of simulated data sets. The effect of gene frequency, dominance, model misspecification, marker spacing, and informativeness are also considered in a smaller set of simulations. Within the context of the models examined, the MIM approach was found to be comparable in power with parametric multipoint linkage analysis when (a) parental data are unknown, (b) the effect of the major locus is small and there is additional genetic variation, or (c) the parameters of the major-locus model are misspecified. The performance of the MIM method relative to MLINK was markedly lower when the allele frequency at the trait locus was .2 versus .5, particularly for the case when parental data were assumed to be known. Dominance at the trait major locus, as well as marker spacing and heterozygosity, did not appear to have a large effect on the ELOD comparisons.
 ...
PMID:Comparison of a multipoint identity-by-descent method with parametric multipoint linkage analysis for mapping quantitative traits. 153 96

Indices of bone mass were measured in 23 volunteers weekly over 14-16 weeks using dual-energy x-ray absorptiometry (DEXA) and special-purpose computed tomography (gamma-CT). In vitro, the precision for both systems was excellent (coefficient of variation less than 0.5%). Over 4 months, the precision in vivo (average CV for all subjects) for DEXA measures (BMD, g/cm2, and BMC, g/cm) varied between 0.6 and 1.1%; with gamma-CT it varied from 1.1% for TBD (g/cm3) to 2.2% for CBD (g/cm3). Correlation between the indices of bone mass measured using DEXA and gamma-CT at the ultradistal site was moderate, but these indices were not correlated at the distal third site. When BMD and BMC were derived from the CT index IBD, however, the correlation between these gamma-CT indices and the corresponding DEXA indices was high for both ultradistal and proximal radial sites.
 ...
PMID:Bone mass measurements in the distal forearm using dual-energy x-ray absorptiometry and gamma-ray computed tomography: a longitudinal, in vivo comparative study. 160 26

A double-antibody sandwich ELISA was employed for detection of IBD virus in bursal suspension. Fifty IBD-free white leghorn chickens aged 5 weeks were experimentally infected with IBD virus. Bursae were collected 4, 8, 12, 24, 36 and 48 hours and 3, 4 and 5 days post-infection. An equal number of chickens acted as appropriate controls. The colour difference between a positive and a negative reaction was clearly distinguished with the naked eye. The cut-off level between ELISA negative and ELISA positive absorbance values was estimated at mean absorbance of negative controls plus three times the standard deviation.
 ...
PMID:Double-antibody sandwich ELISA for detection of infectious bursal disease virus. 165 48

Azathioprine (AZ) has been used in the treatment of refractory inflammatory bowel disease. The mechanism by which AZ decrease colonic inflammation is not known. It is alluded that AZ may be effective in the maintenance of remission. We examined whether AZ in non-immunosuppressive doses reduces extravasation and neutrophil trafficking in a rat model of colonic inflammation. Rats were treated with I.P. injection of AZ (1 mg/kg) for 6 weeks. At the end of 2 and 6 weeks rats were injected I.V. immune complex and on the following day the proximal colon was perfused with 2.5% formaldehyde (local irritant 3 ml/hour for 5 mins). Extravasation was measured by Evans' blue technique and neutrophil concentration in the tissue was determined by measuring myeloperoxidase (MPO). AZ did not inhibit extravasation and MPO after 2 weeks of therapy. However, after 6 weeks, AZ reduced extravasation to 20 +/- 2 micrograms/gm compared to untreated animals (51 +/- 6 micrograms/gm tissue) and MPO levels to 0.3 +/- 13 compared to untreated rats (0.8 +/- 0.32 mU/gm). There was a good correlation between extravasation and MPO levels. These results suggest that long-term treatment with AZ may prevent extravasation and cause reduction in neutrophil trafficking. Such an effect may be beneficial for maintaining remission in IBD.
 ...
PMID:Azathioprine reduces extravasation and neutrophil trafficking in immune complex-mediated inflammation in the rat colon. 166 97

There is a growing body of experimental data to suggest that the chronically inflamed intestine and/or colon may be subjected to considerable oxidative stress. The most probable sources of these oxidants are the phagocytic leukocytes since these cells are known to be present in large numbers in the inflamed mucosa and are known to produce significant amounts of reactive oxygen species in response to certain inflammatory stimuli. Because the colonic mucosa contains relatively small amounts of antioxidant enzymes (e.g. SOD, catalase, GSH peroxidase) it is possible that the gut mucosa may be overwhelmed during times of active inflammation which could result in intestinal injury. If reactive oxygen species play an important role in mediating mucosal injury in IBD then it should be possible to attenuate this injury by the use of antioxidants. One such drug is the sulfasalazine metabolite 5-ASA. It may not be coincidence that this potent antiinflammatory metabolite is a potent antioxidant that possesses multiple mechanisms of action including nitrogen, carbon and oxygen-centered free radical scavenging properties as well as the ability to decompose HOCl and scavenge hemoprotein-associated oxidants. In addition 5-ASA has the additional property of being able to chelate iron and render it poorly redox active. The reason that 5-ASA is so effective in vivo may be due to this multitude of antioxidant properties. This would also suggest that other, more potent antioxidants may prove beneficial in the treatment of IBD.
 ...
PMID:Role of neutrophil-derived oxidants in the pathogenesis of intestinal inflammation. 166 88

Infectious bursal disease was reported in a flock of 7-week old vaccinated chickens. Clinical findings and post-mortem changes were classical as well as the microscopic pathology of the bursa. Bursal homogenates from dead birds were positive for IBD virus antigen in agar gel diffusion test (AGDT). Convalescent sera obtained from birds 14 days following the onset of clinical signs were also positive for IBD virus antibody in AGDT. Seven-week old susceptible birds, each infected i/m with 0.1 ml of a bursal preparation from the outbreak, showed clinical signs of IBD on the 3rd day and were all dead by the 6th day. Their bursae were also positive for IBD virus antigen in AGDT. This is the first recorded outbreak of IBD in Southern Nigeria following inoculation with a locally produced vaccine.
 ...
PMID:First report of an infectious bursal disease outbreak in a vaccinated chicken flock in Anambra State, Nigeria. 166 70

As outlined, scanty data exist with regard to immunologic therapy in children with IBD despite the fact that the pediatric population affords a unique opportunity for clinical evaluation. Children are less affected by modifying conditions such as smoking, alcohol ingestion, and the long-term use of medications, and because of their specific needs for ponderal and linear growth, children might benefit most from immunological therapy that has been proven to be steroid sparing. Therefore, clinical trials to evaluate the efficacy of 6-MP and/or azathioprine in growing children with Crohn's disease would appear to provide a fruitful avenue for collaborative research. Efforts to organize a multicenter evaluation of these agents have been initiated. The studies are crucial in evaluating the efficacy and safety of immunosuppressive therapy in the pediatric population with IBD.
 ...
PMID:Immunology of inflammatory bowel disease: summary of the proceedings of the Subcommittee on Immunosuppressive Use in IBD. 167 6

Pronounced changes in gut neuropeptide content and innervation patterns have been observed in the inflamed intestine of patients with inflammatory bowel disease. It is not known to date whether these changes in neuropeptides are due to altered synthesis and release from intrinsic and/or extrinsic neurons and nerve fibers. The changes in circular smooth muscle response associated with diminished VIP in the intestine of patients with Crohn's disease suggests that VIP may play an important role in the pathophysiology of motility in IBD. The pronounced increase in SP receptors at small vessels in all gut layers and at lymph nodules in the inflamed intestine of IBD patients supports the hypothesis that SP is a modulator of inflammation in IBD and possibly acts by release from extrinsic sensory nerves of the gut. Sensory nerve may play a role not only in enhancing an inflammatory response in the intestine, but also in tissue repair. An inflammatory response after tissue injury and subsequent wound healing presumably is the normal response in healthy tissue. In IBD however, this sequence may be deeply disturbed by an unrestricted immune response which does not lead to or delays intestinal tissue healing. Although it is intriguing to postulate that interactions between the immune system and nervous system exist and play a role in the pathophysiology of intestinal inflammation, in vivo studies blocking or mimicking neuropeptide action are needed to prove this bidirectional communication.
 ...
PMID:Neuropeptides and inflammatory bowel disease. 171 64

We randomly surveyed 997 members of the Crohn's and Colitis Foundation of America with inflammatory bowel disease (320 ulcerative colitis and 671 Crohn's disease) in order to: (1) assess their health status, (2) compare members with ulcerative colitis and Crohn's disease, and (3) determine the correlates of health care use. Data collection included variables relating to physical and psychological symptoms, medication use, daily functional status, perceptions of health, and coping styles. The findings indicate that: (1) despite a number of symptoms and complications related to inflammatory bowel disease, the health status of this population is generally good and may be a result of effective coping styles; (2) those with Crohn's disease have more psychosocial difficulties, which appear related to greater symptom severity; (3) both psychosocial and physical health variables are related to number of physician visits, while primarily physical health variables are related to number of hospitalizations and surgeries. Further studies are needed to determine the representativeness of this self-selected sample with others having IBD. In this study, we have provided the basis for developing a more sensitive measure of health status than currently exists, and one which may have implications for future clinical studies.
 ...
PMID:Health status and health care use in persons with inflammatory bowel disease. A national sample. 174 45

Cases of interest using affected sib-pair methods to distinguish between recessive and additive (dominant) modes of inheritance of a disease-predisposing gene involve goodness-of-fit tests with a small expected number in the "share-zero parental haplotypes" category, as well as an unknown parameter, the frequency of the disease-predisposing allele. Our simulations demonstrate that the real significance level of the chi-square test using the three-haplotype-sharing IBD values (share 2, 1, and 0 parental haplotypes) is close to the assumed (.05) level in these cases, so that the haplotype-sharing classes do not have to be lumped, which would leave no degrees of freedom for a statistical test. The validity of the chi-square approximation in cases of small expected frequencies has previously been described, but the situations that have been considered do not cover the very small values in the share-zero category that are often expected in the affected sib-pair analysis, nor do they involve estimation of an unknown parameter. Although including IBD values from affected kin pairs other than sibs can be a very powerful tool in demonstrating linkage of a marker and disease, these pairs do not add power, in fact they reduce the power, of the chi-square tests of goodness-of-fit of modes of inheritance.
 ...
PMID:Affected kin-pair IBD methods: genetic models. 176 Dec 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>